三叶香茶菜对四氯化碳致肝纤维化大鼠TLR4信号通路的影响

Effect of Herba Isodonis Ternifoliae on Toll-like Receptor 4 Pathway in Rats with Hepatic Fibrosis Induced by Carbon Tetrachloride

目的探讨三叶香茶菜对四氯化碳(CCl_4)致肝纤维化大鼠toll样受体-4(TLR4)信号通路的影响。方法采用CCl4致肝纤维化大鼠模型,生化检测血清谷丙转氨酶(ALT)、谷草转氨酶水平(AST),HE、Masson染色病理检查评价三叶香茶菜对肝组织的保护作用,酶联免疫吸附实验检测血清白细胞介素(IL)-1β、肿瘤坏死因子-α(TNF-α)水平,荧光定量PCR法检测大鼠肝组织TLR4m RNA、My D88m RNA的表达。结果三叶香茶菜能够显著抑制肝纤维化大鼠血清ALT和AST的水平,改善大鼠肝组织纤维化,抑制肝纤维化大鼠IL-1β、TNF-α的表达,对肝纤维化大鼠肝组织TLR4 m RNA的表达具有显著的下调作用,与模型对照组比较,差异均具有统计学意义(P<0.05,P<0.01),对My D88 m RNA的表达无显著抑制作用(P>0.05)。结论三叶香茶菜对CCl4致大鼠肝纤维化具有一定的抑制作用,机制之一是下调TLR4信号通路的活化。

Objective To investigate the effect of Herba Isodonis Ternifoliae on the toll-like receptor 4 （TLR4） pathway of rats with hepatic fibrosis induced by carbon tetrachloride（CCL）. Methods The rats with hepatic fibrosis induced by CCI4 were treated with the ethanol extracts of Herba Isodonis Ternifoliae. Serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） of rats were measured using ultraviolet-visible spectrophotometry, and the protective effect of Herba Isodonis Ternifoliae against hepatic histology was evaluated after HE and Masson staining. Meanwhile, the serum levels of interleukin 1β （IL-1β） and tumor necrosis factor alpha （TNF-a） were detected using enzyme-linked immunosorbent assay （ELISA） , and the expression levels of TLR4 mRNA and MyD88 mRNA in the hepatic tissue were analyzed by real-time quantitative PCR assay. Results Compared with the model group, the ethanol extracts of Herba Isodonis Ternifoliae could significantly reduce the levels of ALT, AST, IL-1β and TNF-a in the serum of rats with hepatic fibrosis, relieve the liver fibrosis, and down-regulate the expression of TLR4 mRNA in liver tissue of hepatic fibrosis rats（P 〈 0.05）. However, the ethanol extracts of Herba lsodonis Ternifoliae showed no inhibition on the expression of MyD88 mRNA in liver tissue of hepatic fibrosis rats. Conclusion Herba Isodonis Ternifoliae shows certain protective effect against hepatic fibrosis induced by CC14 in rats, and down-regulation of the activation of TLR4 pathway may be one of its therapeutic mechanisms.