摘要
目的探讨坎地沙坦酯对酒精性肝纤维化(alcoholic liver fibrosis,ALF)小鼠TGF⁃β1/Smads信号通路及相关生化指标的影响。方法将42只C57小鼠随机分为空白对照组(n=8)和模型组(n=34),成功构建ALF小鼠模型后,随机分为模型对照组、阳性对照组和实验组。阳性对照组和实验组分别给予水飞蓟素和坎地沙坦酯干预,其余正常饲养。干预结束后,异氟烷吸入麻醉小鼠,腹主动脉取血,离心,ELISA法检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和甘油三酯(TG)的水平,解剖分离肝脏,计算肝脏指数;并切取部分肝组织制作石蜡切片,苏木精-伊红和天狼星红染色,光镜下观察病理改变,其余肝组织裂解、匀浆,分离上清液,Western blot检测TGF⁃β1和Smad3蛋白的表达水平,TR⁃PCR检测TGF⁃β1 mRNA和Smad3 mRNA水平。结果光镜下可见,模型对照组小鼠肝组织局部可见大量炎性细胞浸润、出血、肝细胞坏死和胶原沉积;模型对照组ALT、AST和TG水平显著高于空白对照组、阳性对照组和实验组,差异均有统计学意义(P<0.01),阳性对照组与实验组ALT、AST和TG水平无明显差异,差异无统计学意义(P>0.05);肝脏指数、TGF⁃β1和Smad3蛋白的表达水平和TGF⁃β1 mRNA和Smad3 mRNA水平均与上述统计结果一致。结论实验结果表明,坎地沙坦酯可以改善肝纤维化,降低血清ALT、AST和TG水平,并通过抑制TGF⁃β1/Smads信号通路关键分子表达而发挥作用。
Objective To investigate the effects of candesartan on TGF⁃β1/Smads signaling pathway and related biochemical markers in alcoholic liver fibrosis(ALF)mice models.Method A total of42 C57 mice were randomly divided into the Control Group(n=8)and the Model Group(n=34).After successfully constructing ALF model,they were randomly split into Model Control Group(MCG),Positive Control Group(PCG)and Experimental Group(EG).Mice in the PCG and the EG were given silymarin and candesartan respectively while the rest in the MCG were reared normally.After the intervention,the blood of mice was taken from the abdominal aorta,centri⁃fuged,ELISA was used to detect serum aspartate transaminase(ALT),alanine transaminase(AST)and triacylg⁃lycerol(TG)levels.The livers were dissected;The liver index was calculated.Part of liver tissue was used to make paraffin sections.HE and Sirius red stain,pathological changes were observed under light microscope.The others were used to detect the expression levels of TGF⁃β1 mRNA,Smad3 mRNA,TGF⁃β1 and Smad3 protein.Results Under light microscopy,plenty of inflammatory cells,hemorrhage,hepatocyte necrosis and collagen deposition were observed in the liver tissue of the model control group.The levels of ALT,AST and TG in the MCG were statistical⁃significantly higher than those in other groups(P<0.01),but there was no significant difference in the levels of ALT,AST and TG between the PCG and the EG(P>0.05).Interestingly,the liver index,TGF⁃β1 and Smad3 protein expression levels and TGF⁃β1 mRNA and Smad3 mRNA levels were consistent with the above statistical results.Conclusion The results suggest that candesartan can improve liver fibrosis,reduce serum ALT,AST and TG levels,and play a role in improving fibrosis by inhibiting the expression of key molecules in the TGF⁃β1/Smads signaling pathway.
作者
徐旭东
段光琦
刘洁
杨辉
钱叶本
XU Xudong;DUAN Guangqi;LIU Jie;YANG Hui;QIAN Yeben(The First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;Yijishan Hospital of Wannan Medical college,Wuhu 241001,China)
出处
《实用医学杂志》
CAS
北大核心
2020年第3期305-310,共6页
The Journal of Practical Medicine
基金
安徽省自然科学基金项目(编号：1508085MH173)
北京医卫健康公益基金会医学科学研究基金项目(编号：F3211C)
