杠板归总黄酮对抗结核药物致肝损伤小鼠的保护作用及机制研究

Protective effect and mechanism of total flavonoids extracted from Polygonum perfoliatum L. on liver injury induced by antituberculosis drug in mice

目的:研究杠板归总黄酮对抗结核药物致肝损伤小鼠的保护作用,并探索作用机制。方法:将60只小鼠随机分为6组,即正常组、模型组、葡醛内酯组(200 mg/kg)及杠板归总黄酮组(600 mg/kg,300 mg/kg,150 mg/kg)。除正常组外,其余各组均灌胃异烟肼和利福平各100 mg/kg造模,同时给予杠板归总黄酮干预,每天1次。第30天,取血和肝组织,采用生化法检测血清中ALT和AST活性;酶联免疫吸附法(ELISA)检测肝组织TNF-α、IL-1β和IL-6含量;Western Blot检测肝组织Fas表达;HE染色进行肝组织病理学检查。结果:与模型组相比,杠板归总黄酮(600 mg/kg、300mg/kg)能够明显降低肝损伤小鼠血清中ALT和AST活性,明显抑制肝组织TNF-α、IL-1β、IL-6和Fas表达,并改善肝组织病变,而杠板归总黄酮组150 mg/kg对抗结核药物致肝损伤无改善作用。结论:杠板归总黄酮可保护异烟肼和利福平联用导致的肝损伤小鼠,其机制可能与抑制Fas通路和抗炎作用有关。

Objective： To investigate the protective effect and mechanism of total flavonoids extracted from Polygonum perfoliatum L.（TFP） on the liver injury induced by antituberculosis drug in mice. Methods： Sixty mice were divided into the control group,the model group,200 mg/kg glucurolactone group,TFP groups（600,300,150 mg/kg）. Expect the control group,mice in other groups were given intragastric administration of isoniazid and rifampicin（100 mg/kg） which induced liver injury,and were simultaneously treated with corresponding agents,once a day. On the thirty day,the blood and livers were collected. Activities of ALT and AST were detected by the biochemical technology,contents of TNF-α,IL-1β and IL-6 were detected by enzyme linked immunosorbent assay（ELISA）,the expression of Fas protein by Western Blot,and pathological changes of liver tissue was examined by HE staining. Results： Compared with the model group,TFP（600 mg/kg,300 mg/kg） reduced activities of serum ALT and AST,inhibited expressions of TNF-α,IL-1β,IL-6 and Fas in liver tissues,and improved pathological changes of liver tissue,While 150 mg/kg TFP had no significant improvement. Conclusion： TFP could improve the liver injury in mice induced by isoniazid and rifampicin via inhibiting Fas pathway and inflammatory response.