Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China.In this study,we investigated the protective effect and underlying mechanisms GXB in typeⅡdiabetes with a...Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China.In this study,we investigated the protective effect and underlying mechanisms GXB in typeⅡdiabetes with acute myocardial ischemia(T2DM-AMI)rats.We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells(EPCs)apoptosis via activating PI3K(phosphatidyl inositol 3-kinase)/Akt(serine/threonine protein kinase B)/e NOS(endothelial nitric oxide synthase)signaling.Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of typeⅡdiabetes mellitus(T2DM)and coronary ligation to induce acute myocardial infarction(AMI).Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination.The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry.Target m RNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis.The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose,muscular enzymes,and blood lipids,and reduced oxidative stress.Furthermore,EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased m RNA and protein levels of PI3K,Akt,and eNOS compared to the controls.Conversely,T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis,combined with increased m RNA and protein levels of PI3 K,Akt,and eNOS compared to those of untreated T2DM-AMI rats.Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.展开更多
Objective: To assess the effects of traditional Chinese medicine YiQiFuMai on cardiac function during the progression of ischemic heart failure. Methods: Rabbits were divided into sham, heart failure, and YiQiFuMai gr...Objective: To assess the effects of traditional Chinese medicine YiQiFuMai on cardiac function during the progression of ischemic heart failure. Methods: Rabbits were divided into sham, heart failure, and YiQiFuMai groups. The ischemic heart failure model was established in New Zealand white rabbits, which were intraperitoneally injected with YiQiFuMai injection and 0.9% sodium chloride after the operation. After six weeks, cardiac function was examined by ultrasound;serum BNP levels were measured by ELISA;p-AKT, eNOS, ICAM-1 and VEGF levels were evaluated by real-time PCR and Western-Blot;pathological changes of the myocardial tissue were observed by H&E staining;CD31 expression in tissue samples was analyzed by immunohistochemistry. The ultrastructure and microcirculation of myocardial tissue specimens from the three groups were assessed by transmission electron microscopy. Results: YiQiFuMai decreased serum BNP levels, and increased LVEF and reduced LVEDD at 6 weeks postoperatively. In addition, YiQiFuMai can improve myocardial damage and microcirculation structure, as assessed by histology and transmission electron microscope. At the molecular level, treatment with YiQiFuMai resulted in increased eNOS, VEGF and p-AKT levels but reduced ICAM-1 amounts compared with the heart failure group. Conclusion: Ischemic heart failure damages the microvascular structure and functions of the myocardium. Treatment with YiQiFuMai potentially ameliorates microcirculatory damage and alleviates cardiac failure by improving endothelial function and angiogenesis, and inhibiting inflammatory cell adhesion.展开更多
Objective To investigate the influence of electroacupuncture(EA)on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)signaling pathway in spontaneously hyperten...Objective To investigate the influence of electroacupuncture(EA)on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)signaling pathway in spontaneously hypertensive rats(SHRs).Methods Eight Wistar-Kyoto rats were used as the healthy blood pressure(BP)control(normal group),and 32 SHRs were randomized into model group,EA group,EA plus ghrelin group(EA+G group),and EA plus PF04628935 group(a potent ghrelin receptor blocker;EA+P group)using a random number table.Rats in the normal group and model group did not receive treatment,but were immobilized for 20 min per day,5 times a week,for 4 continuous weeks.SHRs in the EA group,EA+G group and EA+P group were immobilized and given EA treatment in 20 min sessions,5 times per week,for 4 weeks.Additionally,1 h before EA,SHRs in the EA+G group and EA+P group were intraperitoneally injected with ghrelin or PF04628935,respectively,for 4 weeks.The tail-cuff method was used to measure BP.After the 4-week intervention,the rats were sacrificed by cervical dislocation,and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of ghrelin,nitric oxide(NO),endothelin-1(ET-1)and thromboxane A2(TXA2)in the serum.Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation.Western blot was used to measure the expression of PI3K,Akt,phosphorylated Akt(p-Akt)and eNOS proteins in the abdominal aorta.Further,quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to measure the relative levels of mRNA expression for PI3K,Akt and eNOS in the abdominal aorta.Results EA significantly reduced the systolic BP(SBP)and diastolic BP(DBP)(P<0.05).HE staining showed that EA improved the morphology of the vascular endothelium to some extent.Results of ELISA indicated that higher concentrations of ghrelin and NO,and lower concentrations of ET-1 and TXA2 were present in the EA group(P<0.05).The isolated 展开更多
For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fa...For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility.However,vascular graft with single layer is difficult to adapt to the complex internal environment.In this work,polycaprolactone(PCL)and sulfated SF were used to fabricate bilayer vascular graft(BLVG)to mimic the structure of natural blood vessels.To enhance the biological activity of BLVG,nicorandil(NIC),an FDA-approved drug with multi-bioactivity,was loaded in the BLVG to fabricate NIC-loaded BLVG.The morphology,chemical composition and mechanical properties of NIC-loaded BLVG were assessed.The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior.The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation,migration and antioxidation capability of endothelial cells(ECs).Moreover,we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway.Overall,the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81173164 and 81573852)the Public Service Key Project of Shandong Provincial Research and Development(No.2018GSF119009)。
文摘Gualou-Xiebai-Banxia decoction has a long history of medical use for treating cardiovascular diseases in China.In this study,we investigated the protective effect and underlying mechanisms GXB in typeⅡdiabetes with acute myocardial ischemia(T2DM-AMI)rats.We hypothesized that GXB may display its protective effect on T2DM-AMI by reducing endothelial progenitor cells(EPCs)apoptosis via activating PI3K(phosphatidyl inositol 3-kinase)/Akt(serine/threonine protein kinase B)/e NOS(endothelial nitric oxide synthase)signaling.Rats were challenged with a high-fat diet and intraperitoneal injection of streptozotocin to induce a model of typeⅡdiabetes mellitus(T2DM)and coronary ligation to induce acute myocardial infarction(AMI).Changes in metabolites were assessed via enzyme-linked immunoassay and biochemical examination.The number and apoptosis rate of EPCs in peripheral blood were detected by flow cytometry.Target m RNAs and proteins in EPCs were analyzed by RT-PCR and Western blot analysis.The results demonstrated that GXB treatment decreased T2DM-AMI-associated changes in plasma fasting blood glucose,muscular enzymes,and blood lipids,and reduced oxidative stress.Furthermore,EPC apoptosis was increased in T2DM-AMI rats and was associated with decreased m RNA and protein levels of PI3K,Akt,and eNOS compared to the controls.Conversely,T2DM-AMI rats treated with GXB exhibited more circulating EPCs and downregulated levels of cell apoptosis,combined with increased m RNA and protein levels of PI3 K,Akt,and eNOS compared to those of untreated T2DM-AMI rats.Our study showed that GXB treatment mitigated EPC apoptosis and promoted PI3K/Akt/eNOS signaling in T2DM-AMI rats.
文摘Objective: To assess the effects of traditional Chinese medicine YiQiFuMai on cardiac function during the progression of ischemic heart failure. Methods: Rabbits were divided into sham, heart failure, and YiQiFuMai groups. The ischemic heart failure model was established in New Zealand white rabbits, which were intraperitoneally injected with YiQiFuMai injection and 0.9% sodium chloride after the operation. After six weeks, cardiac function was examined by ultrasound;serum BNP levels were measured by ELISA;p-AKT, eNOS, ICAM-1 and VEGF levels were evaluated by real-time PCR and Western-Blot;pathological changes of the myocardial tissue were observed by H&E staining;CD31 expression in tissue samples was analyzed by immunohistochemistry. The ultrastructure and microcirculation of myocardial tissue specimens from the three groups were assessed by transmission electron microscopy. Results: YiQiFuMai decreased serum BNP levels, and increased LVEF and reduced LVEDD at 6 weeks postoperatively. In addition, YiQiFuMai can improve myocardial damage and microcirculation structure, as assessed by histology and transmission electron microscope. At the molecular level, treatment with YiQiFuMai resulted in increased eNOS, VEGF and p-AKT levels but reduced ICAM-1 amounts compared with the heart failure group. Conclusion: Ischemic heart failure damages the microvascular structure and functions of the myocardium. Treatment with YiQiFuMai potentially ameliorates microcirculatory damage and alleviates cardiac failure by improving endothelial function and angiogenesis, and inhibiting inflammatory cell adhesion.
基金This study was supported by the National Natural Science Foundation of China(No.81704137.No.82074516,and No.82104976)sichuan Science and Technology Department(No.2019YJ0331)Chengdu University of Traditional Chinese Medicine(No.ZRQN2020022).
文摘Objective To investigate the influence of electroacupuncture(EA)on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)signaling pathway in spontaneously hypertensive rats(SHRs).Methods Eight Wistar-Kyoto rats were used as the healthy blood pressure(BP)control(normal group),and 32 SHRs were randomized into model group,EA group,EA plus ghrelin group(EA+G group),and EA plus PF04628935 group(a potent ghrelin receptor blocker;EA+P group)using a random number table.Rats in the normal group and model group did not receive treatment,but were immobilized for 20 min per day,5 times a week,for 4 continuous weeks.SHRs in the EA group,EA+G group and EA+P group were immobilized and given EA treatment in 20 min sessions,5 times per week,for 4 weeks.Additionally,1 h before EA,SHRs in the EA+G group and EA+P group were intraperitoneally injected with ghrelin or PF04628935,respectively,for 4 weeks.The tail-cuff method was used to measure BP.After the 4-week intervention,the rats were sacrificed by cervical dislocation,and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin(HE)staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of ghrelin,nitric oxide(NO),endothelin-1(ET-1)and thromboxane A2(TXA2)in the serum.Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation.Western blot was used to measure the expression of PI3K,Akt,phosphorylated Akt(p-Akt)and eNOS proteins in the abdominal aorta.Further,quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to measure the relative levels of mRNA expression for PI3K,Akt and eNOS in the abdominal aorta.Results EA significantly reduced the systolic BP(SBP)and diastolic BP(DBP)(P<0.05).HE staining showed that EA improved the morphology of the vascular endothelium to some extent.Results of ELISA indicated that higher concentrations of ghrelin and NO,and lower concentrations of ET-1 and TXA2 were present in the EA group(P<0.05).The isolated
基金This work was supported by the National Natural Science Foundation of China(31771058,32071359,11421202,61227902 and 11120101001)NationalKey Technology R&D Program(2016YFC1100704,2016YFC1101101)+3 种基金International Joint Research Center of Aerospace Biotechnology and Medical Engineering from Ministry of Science and Technology of China111 Project(B13003)Research Fund for the Doctoral Program of Higher Education of China(20131102130004)Fundamental Research Funds for the Central Universities.
文摘For the surgical treatment of cardiovascular disease(CVD),there is a clear and unmet need in developing small-diameter(diameter<6 mm)vascular grafts.In our previous work,sulfated silk fibroin(SF)was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility.However,vascular graft with single layer is difficult to adapt to the complex internal environment.In this work,polycaprolactone(PCL)and sulfated SF were used to fabricate bilayer vascular graft(BLVG)to mimic the structure of natural blood vessels.To enhance the biological activity of BLVG,nicorandil(NIC),an FDA-approved drug with multi-bioactivity,was loaded in the BLVG to fabricate NIC-loaded BLVG.The morphology,chemical composition and mechanical properties of NIC-loaded BLVG were assessed.The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior.The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation,migration and antioxidation capability of endothelial cells(ECs).Moreover,we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway.Overall,the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
