摘要
目的:观察芪参汤对肝纤维化大鼠PI3K/Akt/mTOR信号通路的影响;方法:40只SD大鼠随机分为空白组、模型组、芪参汤组和秋水仙碱组,除空白组外,其余3组均采用四氯化碳腹腔注射构建肝纤维化模型。造模结束后芪参汤和秋水仙碱组给予相应的药物灌胃治疗,模型组及空白组给予等体积蒸馏水灌胃,疗程8周。治疗结束后收集各组腹主动脉血和肝组织,采用ELISA法检测肝功能指标和羟脯氨酸含量,HE和Masson染色检测肝组织病理学形态,免疫组化法检测α-SMA蛋白的表达水平,Western blot检测α-SMA、Col-I、Col-Ⅲ和PI3K/Akt/mTOR信号通路中关键蛋白的表达丰度。结果:与模型组相比,芪参汤能明显降低肝纤维化大鼠AST、ALT、TBIL和Hyp含量,降低炎症评分、纤维化评分、胶原染色面积,差异均具有统计学意义(P<0.05)。同时,芪参汤能明显降低肝纤维化大鼠肝组织中α-SMA、Col-I及Col-Ⅲ蛋的表达水平,差异均具有统计学意义(P<0.05)。与模型组相比,芪参汤能明显降低肝纤维化大鼠肝组织中p-PI3K、p-Akt和p-mTOR蛋白的表达,差异均具有统计学意义(P<0.05)。结论:芪参汤通过抑制PI3K/Akt/mTOR信号通路的活化,进而抑制肝组织中胶原沉积,达到治疗肝纤维化的目的。
Objective:To evaluate the effect of Qishen decoction on PI3K/Akt/mTOR signaling pathway in rats with liver fibrosis.Methods:A total of 40 Sprague-Dawley rats were randomly divided into four groups the control group,the model group,Qishen decoction group,and colchicine group.Except the control group,the remaining three groups were used to establish liver fibrosis models by intraperitoneal injection of carbon tetrachloride.After induction of liver fibrosis,Qishen decoction and colchicine group were given corresponding drug treatment by gavage while the model group and the control group were treated with an equal volume of distilled water for 8 weeks.At the end of the treatment,the blood and liver tissues of rats in each group were collected.The liver function indexes and hydroxyproline content were detected by ELISA,and the pathological morphology of liver tissue was evaluated by HE and Masson staining.Immunohistochemical method was used to detectα-SMA protein expression and Western blotting assay to detect the expression ofα-SMA,Col-I,Col-Ⅲand key proteins related to PI3K/Akt/mTOR signaling pathway.Results:Compared with the model group,Qishen decoction markedly reduced the levels of AST,ALT,and TBIL in serum and Hyp content with statistically significant differences(P<0.05),in addition to decreased inflammatory score,fibrosis score,and collagen staining area in liver tissue.Moreover,Qishen decoction significantly reduced the expression level ofα-SMA,CoL-I and Col-Ⅲ,and downregulated the protein levels of p-PI3K,p-Akt and p-mTOR in liver tissue(P<0.05).Conclusion:Qishen decoction suppresses liver fibrosis and inhibits the deposition of collagen in liver tissue by downregulating PI3K/Akt/mTOR signaling pathway.
作者
李硕熙
王炳予
杨磊
李丹丹
袁星星
LI Shuo-xi;WANG Bing-yu;YANG Lei;LI Dan-dan;YUAN Xing-xing(Jiamusi College of Heilongjiang University of traditional Chinese medicine, Jiamusi, Heilongjiang Province, 154000;Nangang Branch of Heilongjiang College of traditional Chinese medicine, Harbin, Heilongjiang, 1500001)
出处
《海南医学院学报》
CAS
2020年第12期905-909,914,共6页
Journal of Hainan Medical University
基金
黑龙江省中医药科研项目(ZHY18-029,ZHY19-061,ZHY19-062)
黑龙江省自然科学基金联合引导项目(LH2019H095)
国家中医药管理局科研项目(2016ZX05)。
