The clinical treatment of joint contracture due to immobilization remains difficult.The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy a...The clinical treatment of joint contracture due to immobilization remains difficult.The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis.The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway,caspase system pathway,matrix metalloproteinase pathway,Ca2+-dependent pathway and autophagy-lysosomal pathway.The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α.This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments.Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.展开更多
Objective: To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflammation and pulmonary fibrosis induced by bleo...Objective: To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflammation and pulmonary fibrosis induced by bleomycin (BLM) in rats. Methods: Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone (DXM) group. Three doses of HSYA (35.6, 53.3, and 80.0 mg?kg–1?day–1) were intraperitoneally (i.p.) injected in rats for 3 weeks after BLM administration and DXM was used as the positive control (n=8 or 12). Arterial blood gas was assayed and morphological changes were observed. Lung mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin (α-SMA) protein distribution in rat lung tissue was observed by immunohistochemistry. Results: On the 7th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure (PaO2) increased (HSYA 80.0 mg?kg–1, P〈0.01) and CO2 partial pressure (PaCO2) decreased (HSYA 53.3, 80.0 mg?kg–1, P〈0.05). Moreover, the mRNA expression of TNF-α, IL-1β, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg?kg–1 groups than those in the model group (all P〈0.05). Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO2 (HSYA 53.3, 80.0 mg?kg–1, P〈0.01), and decreased PaCO2 (53.3 and 80.0 mg?kg–1, P〈0.05). Further, the mRNA expression of TGF-β1, α-SMA, and collagen Ⅰ as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes (53.3, 80.0 mg?kg–1, P〈0.05). Hematoxylin and eosin and Masson's trichrome staining indicated th展开更多
AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were inject...AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a 展开更多
AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.
BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAF...BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAFLD in the general population in Korea.METHODS This nationwide representative cross-sectional study included 31649 individuals aged≥19 years who participated in the Korea National Health and Nutrition Examination Survey between 2015 and 2018.Odds ratios(ORs)and 95%confidence intervals(95%CIs)for MAFLD according to sex-specific quartiles of muscle strength,defined by relative handgrip strength,were calculated using multivariable logistic regression analysis.Additionally,multivariable logistic regression analysis was used to assess the association between muscle strength and probable liver fibrosis in patients with MAFLD.RESULTS Of all the participants,29.3%had MAFLD.The prevalence of MAFLD was significantly higher in the lower muscle strength quartile groups for all participants,sexes,and age groups(P<0.001).A 1.92-fold(OR=1.92,95%CI:1.70–2.16)and 3.12-fold(OR=3.12,95%CI:2.64–3.69)higher risk of MAFLD was observed in the lowest quartile(Q1)group than in the other groups(Q2–Q4)and the highest quartile(Q4)group,respectively.The ORs of MAFLD were significantly increased in the lower muscle strength quartile groups in a dose-dependent manner(P for trend<0.001).These associations persisted in both sexes.An inverse association between muscle strength and the risk of MAFLD was observed in all subgroups according to age,obesity,and diabetes mellitus.In patients with MAFLD,the odds of severe liver fibrosis were higher in Q1(OR=1.83,95%CI:1.25–2.69)than in other groups(Q2–Q4).CONCLUSION Among Korean adults,low muscle strength was associated with an increased risk of MAFLD and liver fibrosis in patients with MAFLD.展开更多
Objective To determine whether acupotomy ameliorates immobilization-induced muscle contracture and fibrosis via Wnt/β-catenin signaling pathway.Methods Thirty Wistar rats were randomly divided into 5 groups(n=6)by a ...Objective To determine whether acupotomy ameliorates immobilization-induced muscle contracture and fibrosis via Wnt/β-catenin signaling pathway.Methods Thirty Wistar rats were randomly divided into 5 groups(n=6)by a random number table,including control,immobilization,passive stretching,acupotomy,and acupotomy 3 weeks(3-w)groups.The rat model of gastrocnemius contracture was established by immobilizing the right hind limb in plantar flexion for 4 weeks.Rats in the passive stretching group received passive stretching at gastrocnemius,a daily series of 10 repetitions for 30 s each at 30-s intervals for 10 consecutive days.Rats in the acupotomy and acupotomy 3-w groups received acupotomy once and combined with passive stretching at gastrocnemius a daily series of 10 repetitions for 30 s each at 30-s intervals for 10 consecutive days.Additionally,rats in the acupotomy 3-w group were allowed to walk freely for 3 weeks after 10-day therapy.After treatment,range of motion(ROM),gait analysis[i.e.,paw area,stance/swing and maximum ratio of paw area to paw area duration(Max dA/dT)],gastrocnemius wet weight and the ratio of muscle wet weight to body weight(MWW/BW)were tested.Gastrocnemius morphometric and muscle fiber cross-sectional area(CSA)were assessed by hematoxylin-eosin staining.Fibrosis-related mRNA expressions(i.e.,Wnt 1,β-catenin,axin-2,α-smooth muscle actin,fibronectin,and types I and III collagen)were measured using real-time quantitative polymerase chain reactions.Wnt 1,β-catenin and fibronectin concentrations were measured by enzyme-linked immunosorbent assay.Types I and III collagen in the perimysium and endomysium were analyzed using immunofluorescence.Results Compared with the control group,ROM,gait function,muscle weight,MWW/BW and CSA were significantly decreased in the immobilization group(all P<0.01),while protein levels of types I and III collagen,Wnt 1,β-catenin,fibronectin and mRNA levels of fibrosis-related genes were obviously increased(all P<0.01).Treatment with passive stretching or acupotom展开更多
In order to investigate the biological function of transforming growth factor-β1(TGF-β1) during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastroc...In order to investigate the biological function of transforming growth factor-β1(TGF-β1) during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ(COL Ⅰ) mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.展开更多
Objective To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupo...Objective To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.展开更多
AIM: To explore this hypothesis that smooth muscle cells may be capable of acquiring a myofibroblastic phenotype, we have studied the expression of smoothelin in fibrotic conditions.
文摘The clinical treatment of joint contracture due to immobilization remains difficult.The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis.The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway,caspase system pathway,matrix metalloproteinase pathway,Ca2+-dependent pathway and autophagy-lysosomal pathway.The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α.This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments.Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
基金Supported by Traditional Chinese Medicine Development Foundation of Beijing(No.JJ-2009-22)Natural Science Foundation of Beijing(No.7132047)
文摘Objective: To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflammation and pulmonary fibrosis induced by bleomycin (BLM) in rats. Methods: Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone (DXM) group. Three doses of HSYA (35.6, 53.3, and 80.0 mg?kg–1?day–1) were intraperitoneally (i.p.) injected in rats for 3 weeks after BLM administration and DXM was used as the positive control (n=8 or 12). Arterial blood gas was assayed and morphological changes were observed. Lung mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin (α-SMA) protein distribution in rat lung tissue was observed by immunohistochemistry. Results: On the 7th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure (PaO2) increased (HSYA 80.0 mg?kg–1, P〈0.01) and CO2 partial pressure (PaCO2) decreased (HSYA 53.3, 80.0 mg?kg–1, P〈0.05). Moreover, the mRNA expression of TNF-α, IL-1β, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg?kg–1 groups than those in the model group (all P〈0.05). Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO2 (HSYA 53.3, 80.0 mg?kg–1, P〈0.01), and decreased PaCO2 (53.3 and 80.0 mg?kg–1, P〈0.05). Further, the mRNA expression of TGF-β1, α-SMA, and collagen Ⅰ as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes (53.3, 80.0 mg?kg–1, P〈0.05). Hematoxylin and eosin and Masson's trichrome staining indicated th
基金Supported by Shanghai Municipal Health Bureau Youth Grant, No. 2008Y032
文摘AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a
基金Supported by Sigrid Juselius Foundationthe Finnish Pediatric Research Foundation
文摘AIM: To study the relation between collagen 1, α-smooth muscle actin (α-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.
文摘BACKGROUND There is limited evidence regarding the association between muscle strength and metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the association between muscle strength and MAFLD in the general population in Korea.METHODS This nationwide representative cross-sectional study included 31649 individuals aged≥19 years who participated in the Korea National Health and Nutrition Examination Survey between 2015 and 2018.Odds ratios(ORs)and 95%confidence intervals(95%CIs)for MAFLD according to sex-specific quartiles of muscle strength,defined by relative handgrip strength,were calculated using multivariable logistic regression analysis.Additionally,multivariable logistic regression analysis was used to assess the association between muscle strength and probable liver fibrosis in patients with MAFLD.RESULTS Of all the participants,29.3%had MAFLD.The prevalence of MAFLD was significantly higher in the lower muscle strength quartile groups for all participants,sexes,and age groups(P<0.001).A 1.92-fold(OR=1.92,95%CI:1.70–2.16)and 3.12-fold(OR=3.12,95%CI:2.64–3.69)higher risk of MAFLD was observed in the lowest quartile(Q1)group than in the other groups(Q2–Q4)and the highest quartile(Q4)group,respectively.The ORs of MAFLD were significantly increased in the lower muscle strength quartile groups in a dose-dependent manner(P for trend<0.001).These associations persisted in both sexes.An inverse association between muscle strength and the risk of MAFLD was observed in all subgroups according to age,obesity,and diabetes mellitus.In patients with MAFLD,the odds of severe liver fibrosis were higher in Q1(OR=1.83,95%CI:1.25–2.69)than in other groups(Q2–Q4).CONCLUSION Among Korean adults,low muscle strength was associated with an increased risk of MAFLD and liver fibrosis in patients with MAFLD.
基金Supported by the Beijing University of Chinese Medicine Research Platform Construction Project(No.2023-JYB-KYPT-11)。
文摘Objective To determine whether acupotomy ameliorates immobilization-induced muscle contracture and fibrosis via Wnt/β-catenin signaling pathway.Methods Thirty Wistar rats were randomly divided into 5 groups(n=6)by a random number table,including control,immobilization,passive stretching,acupotomy,and acupotomy 3 weeks(3-w)groups.The rat model of gastrocnemius contracture was established by immobilizing the right hind limb in plantar flexion for 4 weeks.Rats in the passive stretching group received passive stretching at gastrocnemius,a daily series of 10 repetitions for 30 s each at 30-s intervals for 10 consecutive days.Rats in the acupotomy and acupotomy 3-w groups received acupotomy once and combined with passive stretching at gastrocnemius a daily series of 10 repetitions for 30 s each at 30-s intervals for 10 consecutive days.Additionally,rats in the acupotomy 3-w group were allowed to walk freely for 3 weeks after 10-day therapy.After treatment,range of motion(ROM),gait analysis[i.e.,paw area,stance/swing and maximum ratio of paw area to paw area duration(Max dA/dT)],gastrocnemius wet weight and the ratio of muscle wet weight to body weight(MWW/BW)were tested.Gastrocnemius morphometric and muscle fiber cross-sectional area(CSA)were assessed by hematoxylin-eosin staining.Fibrosis-related mRNA expressions(i.e.,Wnt 1,β-catenin,axin-2,α-smooth muscle actin,fibronectin,and types I and III collagen)were measured using real-time quantitative polymerase chain reactions.Wnt 1,β-catenin and fibronectin concentrations were measured by enzyme-linked immunosorbent assay.Types I and III collagen in the perimysium and endomysium were analyzed using immunofluorescence.Results Compared with the control group,ROM,gait function,muscle weight,MWW/BW and CSA were significantly decreased in the immobilization group(all P<0.01),while protein levels of types I and III collagen,Wnt 1,β-catenin,fibronectin and mRNA levels of fibrosis-related genes were obviously increased(all P<0.01).Treatment with passive stretching or acupotom
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30872627)
文摘In order to investigate the biological function of transforming growth factor-β1(TGF-β1) during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ(COL Ⅰ) mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.
基金supported by the National Natural Science Foundation of China(82074523)the National Natural Youth Science Foundation of China(82004448).
文摘Objective To investigate the effects of acupotomy on skeletal muscle fibrosis and collagen deposition in a rabbit knee osteoarthritis(KOA)model.Methods Rabbits(n=18)were randomly divided into control,KOA,and KOA+acupotomy(Apo)groups(n=6).The rabbits in the KOA and Apo groups were modeled using the modified Videman's method for 6 weeks.After modeling,the Apo group was subjected to acupotomy once a week for 3 weeks on the vastus medialis,vastus lateralis,rectus femoris,biceps femoris,and anserine bursa tendons around the knee.The behavior of all animals was recorded,rectus femoris tissue was obtained,and histomorphological changes were observed using Masson staining and transmission electron microscopy.The expression of transforming growth factor-β1(TGF-β1),Smad 3,Smad 7,fibrillar collagen types I(Col-I)and III(Col-III)was detected using Western blot and real-time polymerase chain reaction(RT-PCR).Results Histological analysis revealed that acupotomy improved the microstructure and reduced the collagen volume fraction of rectus femoris,compared with the KOA group(P=.034).Acupotomy inhibited abnormal collagen deposition by modulating the expression of fibrosis-related proteins and mRNA,thus preventing skeletal muscle fibrosis.Western blot and RT-PCR analysis revealed that in the Apo group,Col-I,and Col-III protein levels were significantly lower than those in the KOA group(both P<.01),same as Col-I and Col-III mRNA levels(P=.0031;P=.0046).Compared with the KOA group,the protein levels of TGF-β1 and Smad 3 were significantly reduced(both P<.01),as were the mRNA levels of TGF-β1 and Smad 3(P=.0007;P=.0011).Conversely,the levels of protein and mRNA of Smad 7 were significantly higher than that in the KOA group(P<.01;P=.0271).Conclusion Acupotomy could alleviate skeletal muscle fibrosis and delay KOA progress by inhibiting collagen deposition through the TGF-β/Smad pathway in the skeletal muscle of KOA rabbits.
基金Supported by In part a grant from the French Ministry of Research
文摘AIM: To explore this hypothesis that smooth muscle cells may be capable of acquiring a myofibroblastic phenotype, we have studied the expression of smoothelin in fibrotic conditions.