Background:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis(SAP),and controlling such inflammation is vital for managing this often fatal disease.Dexmedetomidine ha...Background:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis(SAP),and controlling such inflammation is vital for managing this often fatal disease.Dexmedetomidine has been reported to possess protective properties in inflammatory diseases.Therefore,this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate,and if so,to determine the potential mechanism.Methods:SAP was induced with sodium taurocholate.Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration.α-bungarotoxin,a selective alpha-7 nicotinic acetylcholine receptor(α7nAchR)antagonist,was injected intra-peritoneally 30 min before dexmedetomidine administration.The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine.Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition&Analysis System.Six hours after onset,serum pro-inflammatory cytokine(tumor necrosis factorα[TNF-α]and interleukin 6[IL-6])levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer,respectively.Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.Results:Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α,IL-6,and amylase,strongly alleviating pathological pancreatic injury in the rat model of SAP(TNF-α:174.2±30.2 vs.256.1±42.4 pg/ml;IL-6:293.3±46.8 vs.421.7±48.3 pg/ml;amylase:2102.3±165.3 vs.3186.4±245.2 U/L).However,the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration ofα-bungarotoxin.Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model(discharge frequency:456.8±50.3 vs.332.4±展开更多
Objective:To investigate the effect of Chinese herbal formula Ermiao Powder(二妙散,EMP)on the expression of cholinergic anti-inflammatory pathway in rats with rheumatoid arthritis(RA).Methods:Seventytwo rats were rand...Objective:To investigate the effect of Chinese herbal formula Ermiao Powder(二妙散,EMP)on the expression of cholinergic anti-inflammatory pathway in rats with rheumatoid arthritis(RA).Methods:Seventytwo rats were randomly divided into 6 groups according to body weight,including normal control group,collageninduced arthritis(CIA)group,three doses EMP groups,and methotrexate(MTX)group(n=12 per group).All of the rats except for those in the normal control group were given multipoint subcutaneous injection of bovine typeⅡcollagen to establish a CIA model.Three EMP groups received a high-(4.5 g/kg),medium-(3.0 g/kg),and low-(1.5 g/kg)doses of EMP by intragavage,respectively.MTX group was injected intraperitoneally MTX at 0.9 mg/kg once a week as the positive control.The administration was 3 consecutive weeks.Joint swelling,arthritis index,and body weight changes in different experimental groups of rats were tested.The joint damage was evaluated by masson staining.Quantitative real-time polymerase chain reaction,Western blot,and immunohistochemistry(IHC)were performed to evaluate the expression of CHRNA7,encodingα7 nicotinic acetylcholine receptor in the cholinergic anti-inflammatory pathway,in different tissues and their localization in the spleen and joints.Results:CHRNA7 expression levels were significantly higher in the joints and spleens of CIA group than those in normal control group(both P<0.05).Moreover,the CHRNA7 mRNA and protein levels in the spleen and joints of MTX and three doses of EMP groups were significantly lower than CIA group(all P<0.05).Compared with the MTX group,treatment with low-dose EMP resulted in significant reduction of CHRNA7 mRNA and protein expression levels(P<0.05 or P<0.01).IHC showed positive signals of CHRNA7 in the white pulp and red pulp of the spleens of rats;CHRNA7 was expressed on fibroblast-like synoviocytes,macrophages,and endothelial cells in the joints of rats,and the expression in the joints of low-dose EMP group was significantly lower than that in the CIA group(P<0.展开更多
目的通过建立大鼠肺缺血再灌注损伤(IRI)模型,进行低强度脉冲超声(LIPUS)预处理治疗,探讨IRI后高迁移率蛋白1(HMGB1)在肺组织的表达和LIPUS预处理的保护作用。方法雄性SD大鼠32只,体质量250~300 g,随机分为4组,每组8只。对照组(A组),开...目的通过建立大鼠肺缺血再灌注损伤(IRI)模型,进行低强度脉冲超声(LIPUS)预处理治疗,探讨IRI后高迁移率蛋白1(HMGB1)在肺组织的表达和LIPUS预处理的保护作用。方法雄性SD大鼠32只,体质量250~300 g,随机分为4组,每组8只。对照组(A组),开胸游离左肺门,未行阻断;缺血再灌注组(B组),阻断左肺门45 min后再灌注180 min;预处理组(C组)低强度超声波治疗仪超声定位辐照30 min,然后同B组处理;预处理加α7-烟碱型胆碱能受体(α7n ACh R)拮抗剂组(D组),LIPUS预处理前30 min腹腔注射α7n ACh R拮抗剂甲基牛扁亭2 mg/Kg,然后同预处理组处理。测量肺组织湿干重比值(W/D)和肺通透指数(LPI),大鼠肺组织病理学观察及评分,ELISA法测定肺组织IL1和IL6的浓度,免疫荧光和Western blot检测HMGB1蛋白表达。结果与A组比较,其他三组IR后肺组织W/D值(5.75±0.47)和LPI(2.77±0.18)明显升高(P<0.05),病理学评分(13.31±2.82)明显升高(P<0.05),肺组织IL1(69.13±9.11)和IL6(62.77±8.14)水平明显升高(P<0.05),免疫荧光检测平均IOD值(0.046±0.019)和Western blot检测显示HMGB1表达明显增加(P<0.05)。给于LIPUS预处理后,C组IR后肺组织W/D值(5.07±0.28)和LPI(1.85±0.17)比B组明显降低(P<0.05),病理学评分(8.13±1.76)比B组明显降低(P<0.05),同时肺组织IL1和IL6水平以及HMGB1表达也明显降低,给于α7n ACh R拮抗剂后该作用明显被抑制。结论 LIPUS预处理能够减轻IRI后肺损伤,其机制可能是通过激活依赖α7n ACh R的胆碱能抗炎通路,从而降低肺组织HMGB1的表达。展开更多
基金This work was supported by a grant from the National Natural Sciences Foundation of China(No.81672449)。
文摘Background:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis(SAP),and controlling such inflammation is vital for managing this often fatal disease.Dexmedetomidine has been reported to possess protective properties in inflammatory diseases.Therefore,this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate,and if so,to determine the potential mechanism.Methods:SAP was induced with sodium taurocholate.Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration.α-bungarotoxin,a selective alpha-7 nicotinic acetylcholine receptor(α7nAchR)antagonist,was injected intra-peritoneally 30 min before dexmedetomidine administration.The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine.Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition&Analysis System.Six hours after onset,serum pro-inflammatory cytokine(tumor necrosis factorα[TNF-α]and interleukin 6[IL-6])levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer,respectively.Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.Results:Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α,IL-6,and amylase,strongly alleviating pathological pancreatic injury in the rat model of SAP(TNF-α:174.2±30.2 vs.256.1±42.4 pg/ml;IL-6:293.3±46.8 vs.421.7±48.3 pg/ml;amylase:2102.3±165.3 vs.3186.4±245.2 U/L).However,the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration ofα-bungarotoxin.Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model(discharge frequency:456.8±50.3 vs.332.4±
基金Supported by the National Natural Science Foundation of China(No.81904034)the Basic Research Project of Shanxi Province(No.201801D121228)+1 种基金the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.201804001)the Research Project of Health Commission of Shanxi Province(No.2018001)。
文摘Objective:To investigate the effect of Chinese herbal formula Ermiao Powder(二妙散,EMP)on the expression of cholinergic anti-inflammatory pathway in rats with rheumatoid arthritis(RA).Methods:Seventytwo rats were randomly divided into 6 groups according to body weight,including normal control group,collageninduced arthritis(CIA)group,three doses EMP groups,and methotrexate(MTX)group(n=12 per group).All of the rats except for those in the normal control group were given multipoint subcutaneous injection of bovine typeⅡcollagen to establish a CIA model.Three EMP groups received a high-(4.5 g/kg),medium-(3.0 g/kg),and low-(1.5 g/kg)doses of EMP by intragavage,respectively.MTX group was injected intraperitoneally MTX at 0.9 mg/kg once a week as the positive control.The administration was 3 consecutive weeks.Joint swelling,arthritis index,and body weight changes in different experimental groups of rats were tested.The joint damage was evaluated by masson staining.Quantitative real-time polymerase chain reaction,Western blot,and immunohistochemistry(IHC)were performed to evaluate the expression of CHRNA7,encodingα7 nicotinic acetylcholine receptor in the cholinergic anti-inflammatory pathway,in different tissues and their localization in the spleen and joints.Results:CHRNA7 expression levels were significantly higher in the joints and spleens of CIA group than those in normal control group(both P<0.05).Moreover,the CHRNA7 mRNA and protein levels in the spleen and joints of MTX and three doses of EMP groups were significantly lower than CIA group(all P<0.05).Compared with the MTX group,treatment with low-dose EMP resulted in significant reduction of CHRNA7 mRNA and protein expression levels(P<0.05 or P<0.01).IHC showed positive signals of CHRNA7 in the white pulp and red pulp of the spleens of rats;CHRNA7 was expressed on fibroblast-like synoviocytes,macrophages,and endothelial cells in the joints of rats,and the expression in the joints of low-dose EMP group was significantly lower than that in the CIA group(P<0.
文摘目的通过建立大鼠肺缺血再灌注损伤(IRI)模型,进行低强度脉冲超声(LIPUS)预处理治疗,探讨IRI后高迁移率蛋白1(HMGB1)在肺组织的表达和LIPUS预处理的保护作用。方法雄性SD大鼠32只,体质量250~300 g,随机分为4组,每组8只。对照组(A组),开胸游离左肺门,未行阻断;缺血再灌注组(B组),阻断左肺门45 min后再灌注180 min;预处理组(C组)低强度超声波治疗仪超声定位辐照30 min,然后同B组处理;预处理加α7-烟碱型胆碱能受体(α7n ACh R)拮抗剂组(D组),LIPUS预处理前30 min腹腔注射α7n ACh R拮抗剂甲基牛扁亭2 mg/Kg,然后同预处理组处理。测量肺组织湿干重比值(W/D)和肺通透指数(LPI),大鼠肺组织病理学观察及评分,ELISA法测定肺组织IL1和IL6的浓度,免疫荧光和Western blot检测HMGB1蛋白表达。结果与A组比较,其他三组IR后肺组织W/D值(5.75±0.47)和LPI(2.77±0.18)明显升高(P<0.05),病理学评分(13.31±2.82)明显升高(P<0.05),肺组织IL1(69.13±9.11)和IL6(62.77±8.14)水平明显升高(P<0.05),免疫荧光检测平均IOD值(0.046±0.019)和Western blot检测显示HMGB1表达明显增加(P<0.05)。给于LIPUS预处理后,C组IR后肺组织W/D值(5.07±0.28)和LPI(1.85±0.17)比B组明显降低(P<0.05),病理学评分(8.13±1.76)比B组明显降低(P<0.05),同时肺组织IL1和IL6水平以及HMGB1表达也明显降低,给于α7n ACh R拮抗剂后该作用明显被抑制。结论 LIPUS预处理能够减轻IRI后肺损伤,其机制可能是通过激活依赖α7n ACh R的胆碱能抗炎通路,从而降低肺组织HMGB1的表达。
