【摘要】 目的探讨外源性硫化氢(H2S)对四氯化碳(CCl4)诱导的肝纤维化大鼠的胶原合成和凋亡调节蛋白Bcl-2及Bax的影响。方法将80只SD大鼠随机分为正常对照组、模型对照组、低剂量硫氢化钠(NaHS)组和高剂量NaHS组。处死大鼠后用HE染色及Van Gieson染色观察胶原合成、肝纤维化程度并分级,TUNEL染色了解肝细胞凋亡并以免疫组化法检测细胞凋亡指标Bcl-2及Bax。结果模型对照组大鼠肝胶原合成活跃,肝纤维化程度均达到Ⅲ~Ⅳ期,Bax在第6周末表达达最高峰,而Bcl-2则在第8周末表达达高峰,高剂量和低剂量NaHS组肝胶原合成减少,且肝纤维化程度明显减轻,多处于Ⅰ~Ⅱ期(P<0.01),肝细胞凋亡减少,Bcl-2及Bax的表达下降,与模型对照组比较差异均有统计学意义(P<0.01);并且各指标在高剂量NaHS组与低剂量NaHS组比较差异亦有统计学意义(P<0.01或P<0.05)。此外,至第8周末,高剂量NaHS组部分指标已接近正常。结论外源性H2S可以减少CCl4诱导的大鼠肝纤维化胶原合成,减轻肝纤维化程度,下调凋亡调节蛋白Bcl-2及Bax的表达,发挥重要的抗大鼠肝纤维化作用,且与剂量呈正相关。更多还原

【Abstract】 Objective To detect the influence of exogenous hydrogen sulfide(H2S) on collagen synthesis and expression of Bcl-2 and Bax in rats with hepatic fibrosis. Methods 80 SD rats were randomly divided into four groups: a normal control group, a model control group, a low-dose sodium hydrosulfide(NaHS, 14.4 μmol/kg) group and a high-dose NaHS(36.0 μmol/kg) group. After the experiment, HE stain and Van Gieson stain were used to detect the degree of collagen synthesis and the grade of liver fibrosis, TUNEL stain was used to detect the degree of liver cell apoptosis and immunohistochemistry was used to detect the expression of Bcl-2 and Bax in liver tissue. Results Compared with the model control group, the collagen synthesis decreased(P<0.01), the degree of liver fibrosis lessened(P<0.01) and most of them were graded in Ⅰ or Ⅱ, liver cell apoptosis reduced(P<0.01), and the expression of Bcl-2 and Bax decreased(P<0.01) in the NaHS groups. In addition, there were also statistical significance between high dose NaHS group and low dose NaHS group(P<0.01 or P<0.05). What’s more, some of the results of 8th week were near normal. Conclusion Exogenous hydrogen sulfide can effectively inhibit the development of experimental hepatic fibrosis by decreasing the collagen synthesis, reducing the liver cell apoptosis and decreasing the expression of Bcl-2 and Bax in a positive dosage-dependent manner.更多还原