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芍药苷防治小鼠急性肝损伤的机制研究
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摘要
目的:观察芍药苷(PAE)对四氯化碳(CCl_4)诱导的小鼠急性肝损伤(ALI)的影响及其作用机制。方法:用腹腔注射CCl_4致小鼠急性肝损伤模型,测定不同剂量的PAE对肝损伤血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)活性、肝中炎症和脂肪代谢障碍的影响,同时对肝组织进行病理学检查。结果:PAE具有剂量依赖性地降低CCl_4致小鼠肝损伤血清ALT、AST、白介素1β(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)、甘油三酯(TG)、总胆固醇(TC)和极低密度脂蛋白(VLDL)值升高,下调肝组织匀浆中卜磷酸鞘氨醇(S1P)的含量,抑制肝脏鞘氨醇激酶-1(SphK1)和肝脏核蛋白中核转录因子-kappaB(NF-κB)的蛋白表达水平,并减轻CCl_4对肝脏细胞的病理损伤。结论:PAE对CCl_4诱导的ALI小鼠的保护作用机制可能与抑制SphK1/S1P信号通路表达有关。
[Abstrac]Objective:To investigate the protective effects of Paeoniflorin(PAE) on the mice with acute liver injury(ALI) induced by CC1_4.Methods:The ALI model was prepared by CCU injected intraperitoneally.Then,the therapeutic effects of PAE on the model were evaluated by the activity determination of serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST)and hepatic inflammation and lipid metabolism disorder,and the changes of hepatic pathohistology following the PAE treatment.Result:Following the treatment,PAE reduced the elevated ALT and AST activities and interleukin-1β(IL-1β),IL-6,tumor necrosis factor-a(TNF-α),triglyceride(TG),total cholesterol(TC) and very low density lipoprotein(VLDL) content induced by CC1_4 significantly,and downregulated the sphingosine-1-phosphate levels in liver homogenates,and inhibited hepatic sphingosine kinase 1(SphK1) and nucleoprotein-nuclear transcription factor-kappaB(NF-kB) protein expression.Furthermore,the pathological changes were also significantly improved in the mice of PAE treating group.Conclusion:The protective effects of PAE on the mice with ALI induced by CCL may be related to its inhibition of SphK 1/S1 P signal pathway.
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