中文摘要：

目的探讨瞬时感受器电位离子通道香草素受体亚家族4（transient receptor potential vanilloid receptor4,TRPV4）对肝星状细胞（hepatic stela tecell,HSC）活化增殖的作用及可能的作用机制.方法以含50% CCl4的花生油溶液（1mL·kg^-1）皮下注射,建立大鼠肝纤维化模型.应用蛋白印迹等方法在体观察TRPV4及肌动蛋白α（α-smooth muscleactin,α-SMA）的蛋白表达变化.以转化生长因子-β1（trans-forming growth factor-β1,TGF-β1）（10μg·L^-1）刺激肝星状细胞株（HSC-T6）,离体观察TRPV4及α-SMA的蛋白表达变化.应用TRPV4非特异性抑制剂钌红（rutheniumred,Ru）及TRPV4-siRNA特异性沉默TRPV4,观察HSC-T6增殖及α-SMA、蛋白激酶B（proteinkinaseB,Akt/PKB）蛋白表达变化.结果肝纤维化组织与TGF-β1活化的HSC中TRPV4及α-SMA蛋白表达明显增加.阻断TRPV4可明显抑制HSC增殖,且α-SMA、Akt蛋白表达明显降低.结论TR-PV4参与调控HSC的活化增殖,调控Akt蛋白磷酸化.

英文摘要：

Aim To investigate the effect of TRPV4 on hepatic fibrosis of rats . Methods Liver fibrosis model of rats was induced by 50% CCl4 twice a week for 12 weeks. HE and Masson staining were used to evaluate the degree of hepatic fibrosis, and the levels of α-smooth muscle actin(α-SMA) and TRPV4 were detec-ted in fibrotic liver tissue by Western blot. HSC-T6 cells were activated by transforming growth factor β1 (TGF-β1),and the protein levels of α-SMA, TRPV4 were detected by Western blot. After using Ru and transfected with TRPV4-siRNA, HSC-T6 was stimula-ted with TGF-β1, the levels of α-SMA, TRPV4 and phosphorylation level of Akt were determined by West-ern blot. Results TRPV4 was highly expressed in model liver tissues and in activated HSC-T6 induced by TGF-β1 . The levels of α-SMA and phosphorylation of Akt decreased in TGF-β1-induced HSC, used with Ru or transfected with TRPV4-siRNA. Conclusions The expression of TRPV4 increases in fibrotic livers and ac-tivated hepatic stellate cells. Knockdown of TRPV4 can suppress the activation of hepatic stellate cells in-duced by TGF-β1 , and decrease the phosphorylation levels of Akt.