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小檗碱对何首乌致药物性肝损伤的保护作用

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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-γ 100 μL 和 shRNA-NC 100 μL，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-qPCR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。
Protective effect of berberine against drug-induced hepatic injury caused by Polygonum multiflorum thunb.
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-γ group and PM+BBR+sh-NC group,which were injected with 100 μL of shRNA-PPAR-γ and 100 μL 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-γ expression was knockdown by transfecting shRNA-PPARγ into rats.The expression levels of PPAR-γ in 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-γ expression 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-1β and IL-6 levels were significantly decreased,IL-10 level was significantly increased,and PPAR-γ expression was significantly increased in the PM+BBR group(all P＜0.05).Compared with the PM+BBR+sh-NC group,PPAR-γ expression was significantly decreased,serum ALT,AST,ALP levels were significantly increased,IL-1β and IL-6 levels were significantly increased,IL-10 level was significantly decreased in the PM+BBR+sh-PPAR-γ group(all P＜0.05).CONCLUSION Berberine may alleviate hepatic injury induced by Polygonum multiflorum thunb.by up-regulating PPAR-γ expression.

chemical and drug induced liver injuryberberinePPAR gammainflammation

武冰、田晓鹏、景绍君

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邢台市人民医院肝病科,河北邢台 054000

邢台市人民医院消化科,河北邢台 054000

邢台市人民医院药剂科,河北邢台 054000

化学性与药物性肝损伤 小檗碱 PPARγ 炎症

河北省医学科研项目(2020)

20201576

2024

10.14109/j.cnki.xyylc.2024.07.12

中国新药与临床杂志
中国药学会 上海市食品药品监督管理局科技情报研究所

中国新药与临床杂志

CSTPCD北大核心
影响因子：0.967
ISSN：1007-7669
年,卷(期)：2024.43(7)