小檗碱对何首乌致药物性肝损伤的保护作用  

Protective effect of berberine against drug-induced hepatic injury caused by Polygonum multiflorum thunb.

作　　者：武冰 田晓鹏[2] 景绍君 WU Bing;TIAN Xiao-peng;JING Shao-jun(Department of Hepatology,Xingtai People's Hospital,Xingtai HEBEI 054000,China;Department of Gastroenterology,Xingtai People's Hospital,Xingtai HEBEI 054000,China;Department of Pharmacy,Xingtai People's Hospital,Xingtai HEBEI 054000,China)

机构地区：[1]邢台市人民医院肝病科,河北邢台054000 [2]邢台市人民医院消化科,河北邢台054000 [3]邢台市人民医院药剂科,河北邢台054000

出　　处：《中国新药与临床杂志》2024年第7期547-551,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：2020年度河北省医学科研课题计划(20201576)。

摘　　要：目的探究小檗碱对何首乌致药物性肝损伤的保护作用机制。方法SD大鼠随机分为sham(假手术)组、PM(何首乌40 g·kg^(-1))组、PM+NS(生理盐水1 mL)组和PM+BBR(小檗碱50 mg·kg^(-1))组(均n=12);另选24只大鼠均分为PM+BBR+sh-PPAR-γ组和PM+BBR+sh-NC组,分别尾静脉注射shRNA-PPAR-γ100μL和shRNANC 100μL,持续给药8周。HE染色观察肝组织病理学变化,ELISA法检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)水平及肝组织白细胞介素(IL)-1β、IL-6、IL-10水平。通过RT-q PCR及Western blot法检测大鼠肝组织PPAR-γ表达水平。结果与sham组相比,PM组和PM+NS组血清ALT、AST、ALP水平均显著升高,肝组织IL-1β、IL-6水平显著增加,IL-10水平显著降低,PPAR-γ表达显著下调(均P<0.05)。与PM+NS组相比,PM+BBR组血清ALT、AST、ALP水平显著降低,IL-1β、IL-6水平显著下降,IL-10水平显著上升,PPAR-γ表达显著增加(均P<0.05)。与PM+BBR+sh-NC组相比,PM+BBR+sh-PPAR-γ组PPAR-γ表达显著降低(P<0.05),血清ALT、AST、ALP水平以及肝组织IL-1β、IL-6水平显著增加(P<0.05),IL-10水平显著降低(P<0.05)。结论小檗碱可能通过上调PPAR-γ的表达减轻何首乌诱发的大鼠肝损伤。AIM To investigate the protective mechanism of berberine against Polygonum multiflorum thunb.induced liver injury.METHODS SD rats were randomly divided into sham group,PM(Polygonum multiflorum thunb.40 g·kg^(-1))group,PM+NS(saline 1 mL)group,PM+BBR(berberine 50 mg·kg^(-1))group(n=12 in each group).Another 24 rats were divided into PM+BBR+sh-PPAR-γgroup and PM+BBR+sh-NC group,which were injected with 100μL of shRNA-PPAR-γand 100μL of shRNA-NC into the tail vein.The administration of each group lasted for 8 weeks.HE staining was used to observe the pathological changes in liver tissue,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)levels and the levels of IL-1β,IL-6 and IL-10 in liver tissues were detected by ELISA.PPAR-γexpression was knockdown by transfecting shRNA-PPARγinto rats.The expression levels of PPAR-γin rat liver tissues was detected by RT-qPCR and Western blot.RESULTS Compared with the sham group,the levels of serum ALT,AST,ALP were significantly increased,the levels of IL-1β,IL-6 in liver tissue were increased and IL-10 level was decreased,and PPAR-γexpression was significantly downregulated in the PM group and PM+NS group(all P<0.05).Compared with the PM+NS group,serum ALT,AST,ALP levels were significantly decreased,IL-1βand IL-6 levels were significantly decreased,IL-10 level was significantly increased,and PPAR-γexpression was significantly increased in the PM+BBR group(all P<0.05).Compared with the PM+BBR+sh-NC group,PPAR-γexpression was significantly decreased,serum ALT,AST,ALP levels were significantly increased,IL-1βand IL-6 levels were significantly increased,IL-10 level was significantly decreased in the PM+BBR+sh-PPAR-γgroup(all P<0.05).CONCLUSION Berberine may alleviate hepatic injury induced by Polygonum multiflorum thunb.by up-regulating PPAR-γexpression.

关 键 词：化学性与药物性肝损伤 小檗碱 PPARΓ 炎症 

分 类 号：R978.3[医药卫生—药品]