葡醛内酯对异烟肼和利福平所致肝损伤小鼠肝组织自噬水平的影响

Effect of glucurolactone on the autophagy level of liver tissues in mice with liver injury caused by isoniazid and rifampicin

目的:探究葡醛内酯对异烟肼和利福平所致肝损伤小鼠肝组织自噬水平的影响。方法:取30只SPF级C57B/6J小鼠,灌胃给予异烟肼和利福平(各150 mg/kg)建立肝损伤小鼠模型,并随机分为模型组、低剂量、高剂量组;另取10只为空白组,灌胃给予等体积生理盐水。葡醛内酯低、高剂量组分别按100 mg/kg、200 mg/kg剂量给予葡醛内酯,空白组、模型组给予50 m L/kg生理盐水。给药后,称量小鼠初试、终试体重,计算肝脏脏器系数;苏木精―伊红(HE)染色观察小鼠肝组织形态;比较小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、脂多糖(LPS)水平;电镜观察肝组织中自噬小体数量;实时荧光定量PCR(qPCR)检测小鼠肝组织的自噬相关基因(Atg)5、Atg7、Beclin-1 mRNA表达水平。结果:与模型组相比,葡醛内酯低、高剂量葡醛内酯组小鼠的ALT、AST、LPS水平明显降低,自噬小体数量明显减少,终试体重明显增加,肝脏脏器系数、肝组织中Atg5、Atg7、Beclin-1 m RNA相对表达水平明显升高,肝组织变性坏死程度明显减轻。结论:葡醛内酯对异烟肼和利福平所致的肝损伤具有保护作用,其机制可能与改善肝组织的自噬水平有关。

Objective:To explore the effect of glucurolactone on the level of autophagy in liver tissues of mice with liver injury induced by isoniazid and rifampicin. Methods: Thirty SPF male C57 B/6 J mice were given isoniazid and rifampicin to establish the model of liver injury. The mice were randomly divided into model group, lowdose group and high-dose group. Ten mice were given the same volume of normal saline as blank group. The rats in the low-dose and high-dose groups were given glucurolactone at 100 mg/kg and 200 mg/kg, respectively,while the blank group and model group were given equal volume of normal saline. After administration, the initial and final body weight of mice were weighed, and the liver organ coefficient was calculated;the morphology of liver tissue was observed by HE staining;the levels of liver function in serum were compared;the number of autophagosomes in liver tissue was observed by electron microscope;and the level of Atg5 mRNA, Atg7 mRNA and Beclin-1 mRNA associated with autophagy in liver tissue were detected by RT-qPCR. Results:Compared with the model group, serum ALT, AST, LPS levels and the number of autophagosomes in low and high dose groups were significantly decreased, while the final test weight, liver organ coefficient, the levels of Atg5 mRNA,Atg7 mRNA and Beclin-1 mRNA in liver tissues were significantly increased, and the degree of liver tissue degeneration and necrosis was significantly reduced. Conclusion:Glucurolactone has a protective effect on liver injury induced by isoniazid and rifampicin, and its mechanism may be related to improving the level of autophagy in liver tissue.