五味子甲素对四氯化碳诱导小鼠肝纤维化的保护作用及其机制研究
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篇名: 五味子甲素对四氯化碳诱导小鼠肝纤维化的保护作用及其机制研究
TITLE: Study on the Protective Effects of Schisandrin A on Hepatic Fibrosis Induced by Carbon Tetrachloride in Mice and Its Mechanism
摘要: 目的:研究五味子甲素(SA)对四氯化碳(CCl4)诱导肝纤维化模型小鼠的保护作用及其机制。方法:将小鼠随机分为空白对照组、模型组、水飞蓟素组(阳性对照,100mg/kg)和SA低、高剂量组(20、40mg/kg),每组10只。除空白对照组外,其余组小鼠均采用皮下注射CCl4法建立肝纤维化模型。建模成功后,各给药组小鼠灌胃相应药物,每天1次,连续给药6周;空白对照组和模型组小鼠同法灌胃等体积0.5%羧甲基纤维素钠溶液。采用苏木精-伊红染色法观察小鼠肝组织病理学变化;分别采用紫外分光光度法和酶联免疫吸附法检测小鼠血清肝损伤指标[丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)]水平和炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6]含量;采用Westernblotting法检测小鼠肝组织中NOD样受体蛋白3(NLRP3)/核因子κB(NF-κB)和转化生长因子β(TGF-β)/Smad信号通路蛋白的表达水平。结果:与空白对照组比较,模型组小鼠肝组织纤维化病变明显;血清肝损伤指标水平和炎症因子含量均显著升高(P<0.01);肝组织中NLRP3、凋亡相关斑点样蛋白、胱天蛋白酶1、IL-1β、TGF-β1蛋白表达水平以及磷酸化NF-κBp65(p-NF-κBp65)/NF-κBp65、磷酸化NF-κB抑制蛋白α(p-IκBα)/IκBα、p-Samd3/Smad3比值均显著升高(P<0.01)。与模型组比较,各药物组小鼠肝组织纤维化病变均明显减轻;小鼠血清肝损伤指标水平和炎症因子含量以及肝组织中NLRP3/NF-κB和TGF-β/Smad信号通路蛋白的表达及磷酸化水平均显著降低(P<0.01)。结论:SA可有效减轻CCl4诱导肝纤维化模型小鼠的肝损伤和炎症程度,其可能是通过调节NLRP3/NF-κB和TGF-β/Smad3信号通路从而发挥抑制肝纤维化的作用。
ABSTRACT: OBJECTIVE:To study the pr otective effect of schisandrin A (SA)on CCl 4-induced liver fibrosis model mice and its mechanism. METHODS :Mice were randomly divided into blank control group ,model group ,silymarin group (positive control,100 mg/kg),SA low-dose and high-dose groups (20,40 mg/kg),with 10 mice in each group. Except for blank control group,other groups were given CCl 4 subcutaneously to induce liver fibrosis model. After successful modeling ,administration groups were given relevant medicine intragastrically ,once a day ,for consecutive 6 weeks;blank control group and model group were given constant volume of 0.5%sodium carboxymethyl cellulose solution intragastrically by the same way. HE staining was used to observe the pathological changes of liver tissue in mice. UV spectrophotometry and ELISA assay were adopted to detect the serum levels of liver injury indexes (ALT and AST )and the contents of inflammatory factors (TNF-α,IL-1β,IL-6). Western blotting assay was used to detect the expression of NOD like receptor protein 3(NLRP3)/NF-κB and TGF-β/Smad signaling pathway protein. RESULTS :Compared with blank control group ,obvious pathological changes of liver fibrosis were observed in model group. The serum levels of liver injury indexes and contents of inflammatory factors were significantly increased (P<0.01). The expression of NLRP 3,apoptosis associated spot-like protein ,Caspase-1 and IL- 1β,TGF-β1 and ratios ofp-NF-κB p65/NF-κB p65,p-IκBα/IκBα,p-Samd3/Smad3 were increased significantly (P<0.01). Compared with model group ,SA could significantly relieve hepatic fibrosis in mice ,reduce serum levels of liver injury indexes and contents of inflammatory factors ,as well as the expression of NLRP 3/NF-κB and TGF-β/Smad signaling pathway protein and phosphorylation level(P<0.01). CONCLUSIONS : SA can effectively relieve liver injury and inflammation of CCl 4-induced hepatic fibrosis model mice ,which may be through the regulation of NLRP 3/NF-κB and TGF-β/Smad3 signaling pathways ,thus inhibiting the process of liver fibrosis.
期刊: 2020年第31卷第22期
作者: 王肖辉,周霖,杜秋争,师莹莹,荆自伟,刘丽伟,张俊,李卓伦,贾雪冬,楚尧娟,孙志,左莉华,康建,张晓坚
AUTHORS: WANG Xiaohui,ZHOU Lin,DU Qiuzheng,SHI Yingying,JING Ziwei,LIU Liwei, ZHANG Jun,LI Zhuolun,JIA Xuedong,CHU Yaojuan,SUN Zhi,ZUO Lihua,KANG Jian,ZHANG Xiaojian
关键字: 肝纤维化;五味子甲素;NOD 样受体蛋白3/核因子κB信号通路;转化生长因子β/Smad信号通路;小鼠
KEYWORDS: Liver fibrosis ;Schisandrin A ;NLRP3/NF-κB signaling pathway;TGF-β/Smad signaling pathway;Mice
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