夏枯草硫酸多糖对异烟肼所致小鼠抗结核药物性肝损伤的保护作用及机制

Protective effect and mechanism of prunella vulgaris sulfate polysaccharide on liver injury induced by isoniazid in mice

[目的]分析夏枯草硫酸多糖对异烟肼所致小鼠抗结核药物性肝损伤的保护作用,并探究其可能的机制。[方法]将24只SPF级雄性C57 BL/6小鼠随机分为正常对照组、模型组和实验组,每组8只。模型组和实验组每日定时予以异烟肼100 mg/kg灌胃1次。实验组于异烟肼灌胃前予以夏枯草硫酸多糖100 mg/kg灌胃预处理,每4 d灌胃1次,共3次。异烟肼处理2周后处死小鼠,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性;肝脏匀浆后检测肝组织丙二醛(MDA)、超氧化物歧化酶(SOD)活性;苏木精-伊红染色观察肝脏组织病理形态学的改变;RT-qPCR技术检测肝脏组织白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)mRNA的表达;Western blot技术检测肝脏组织IL-6和TNF-α蛋白的表达。[结果]与正常对照组相比,模型组和实验组小鼠血清AST、ALT活性水平和肝组织MDA含量升高(P<0.001),肝组织SOD活性降低(P<0.001),IL-6和TNF-αmRNA和蛋白表达明显升高(P<0.001),肝组织病理可见不同程度的肝细胞变性坏死及炎细胞浸润。实验组与模型组相比,小鼠血清AST、ALT活性水平和肝组织MDA含量降低,肝组织SOD活性升高(P<0.001),IL-6和TNF-αmRNA和蛋白表达明显降低(P<0.001),肝组织病理改变明显减轻。[结论]夏枯草硫酸多糖对异烟肼所致小鼠抗结核药物性肝损伤具有保护作用,其作用机制可能与抗氧化应激反应、降低炎症反应有关。

[Objective]To analyze the protective effect of prunella vulgaris sulfate polysaccharide on isoniazid-induced liver injury in mice, and to explore its possible mechanism.[Methods]Twenty-four SPF male C57 BL/6 mice were randomly divided into normal control group, model group and experimental group.The model group and the experimental group were administered with isoniazid 100 mg/(kg·d)once a day.The experimental group was given pretreatment with 100 mg/kg of prunella sulfate before the isoniazid administration, gavage every 4 days for a total of three times.Mice were sacrificed 2 weeks after isoniazid treatment, and serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were measured.After liver homogenization, the activity of malondialdehyde(MDA)and superoxide dismutase(SOD)in liver tissues was measured.HE staining was used to observe the pathological changes of liver tissue.RT-qPCR was used to detect the expression of IL-6 and TNF-α mRNA in liver tissue.Western blot was used to detect the expression of IL-6 and TNF-α protein in liver tissues.[Results]Compared with the normal control group, the levels of AST,ALT in serum and MDA in liver tissue increased in the model and experimental groups(P<0.001),SOD activity in liver tissue was decreased(P<0.001),and expression of IL-6 and TNF-α mRNA and protein were significantly increased(P<0.001).The pathological changes of liver tissue showed various degrees of degeneration and necrosis of hepatocytes and infiltration of inflammatory cells.The experimental group was compared with the model group, the levels of AST and ALT in serum and MDA content in liver tissue were decreased, and SOD activity in liver tissue was increased(P<0.001),IL-6 and TNF-α mRNA and protein expression were significantly decreased(P<0.001).The pathological changes of liver tissue were obviously alleviated.[Conclusion]The protective effect of prunella vulgaris sulfate polysaccharide on isoniazid-induced anti-tuberculosis-induced liver injury in mice may be related to antioxidant stress response and reducing inflammatory response.