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目的:研究葛根素对四氯化碳所诱导肝纤维化大鼠的干预作用及其对TLR-4、NF-κB、AP-1的影响。方法:将56只SD大鼠腹腔注射四氯化碳花生油溶液(1∶1)1 mL·kg~(-1),每周2次,连续注射8周,建立肝纤维化大鼠模型。将经病理学检查确认成肝纤维化模型的大鼠随机分为5组:模型组、阳性药水飞蓟素40 mg·kg-1组、葛根素20,40,80 mg·kg~(-1)组,每组10只。每日灌胃给药一次,连续给药60 d。同时另设置正常组大鼠10只。Masson染色法观察各组肝组织病理学变化和纤维化程度。末次给药12 h后,检测大鼠血清谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、白介素-6(IL-6)的水平;Elisa法检测肝组织中肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)的含量;蛋白免疫印迹法检测肝组织中TLR-4、NF-κB、AP-1的蛋白表达。结果 :与模型相比,葛根素可降低肝纤维化大鼠血清AST、ALT、IL-6的水平以及TNF-α、IL-6的含量(P<0.05),并明显下调TLR-4、NF-κB、AP-1的蛋白表达水平(P<0.05)。结论:葛根素具有一定的抗肝纤维化作用,其作用机制可能与调节肝组织中TLR-4、NF-κB、AP-1的蛋白水平有关。
AIM: To investigate the effects of puerarin on carbon tetrachloride-induced hepatic fibrosis in rats and its effect on TLR-4, NF-κB and AP-1. Methods: Fifty-six SD rats were injected intraperitoneally with 1 mL · kg -1 of carbon tetrachloride peanut oil solution twice a week for 8 weeks to establish a rat model of hepatic fibrosis. The pathological examination of liver fibrosis model rats were randomly divided into five groups: model group, the positive silymarin 40 mg · kg -1 group, puerarin 20,40,80 mg · kg -1 group , Each group of 10. Administered once a day, continuous administration of 60 d. At the same time another set of normal group of 10 rats. Masson staining was used to observe the histopathological changes and the degree of fibrosis in each group. The levels of AST, ALT and IL-6 were detected 12 h after the last administration, and the levels of TNF- α and IL-1 were detected by immunohistochemistry. The protein expression of TLR-4, NF-κB and AP-1 in liver tissues were detected by Western blotting. Results: Compared with the model, puerarin decreased the levels of AST, ALT, IL-6, TNF-α and IL-6 in serum of rats with hepatic fibrosis (P <0.05) -κB, AP-1 protein expression levels (P <0.05). CONCLUSION: Puerarin has a certain anti-hepatic fibrosis effect and its mechanism may be related to the regulation of the protein levels of TLR-4, NF-κB and AP-1 in liver tissue.