小檗碱对肝移植术大鼠急性肾损伤的影响及AMPK在其中的作用
Effect of berberine on acute kidney injury in rats undergoing liver transplantation and the role of AMPK
刘成仁 1王刚 1王力 1杨洁 1谭永星 2张可锋 3王永旺1
作者信息
- 1. 桂林医学院附属医院麻醉科,桂林 541001
- 2. 桂林市中医院重症监护室,桂林 541000
- 3. 桂林医学院高发病率防治药理实验室,桂林 541199
- 折叠
摘要
目的 评价小檗碱对肝移植术大鼠急性肾损伤(AKI)的影响及腺苷酸活化蛋白激酶(AMPK)在其中的作用.方法 SPF级成年雄性SD大鼠24只,12周龄,体质量210～230 g,采用随机数字表法分为4组(n=6):假手术组(S组)、AKI组、小檗碱组(BBR组)和小檗碱+AMPK抑制剂Compound C组(BBR-Comp C组).BBR组术前2周开始灌胃给予小檗碱200 mg/kg,1次/d,连续14 d,BBR-Comp C 组术前 30 min 尾静脉注射 Compound C 1 mg/kg.AKI 组、BBR 组和 BBR-Comp C组行原位肝移植术制备大鼠AKI模型.术后24 h时下腔静脉取血标本,采用ELISA法测定血清BUN和Cr浓度;然后处死大鼠取肾组织,HE染色后光镜下观察肾组织病理学结果,采用Western blot法测定磷酸化AMPK(p-AMPK)、受体相互作用蛋白激酶-1(RIPK-1)、受体相互作用蛋白激酶-3(RIPK-3)和混合谱系激酶结构域样蛋白(MLKL)的表达.结果 与S组相比,AKI组血清BUN和Cr浓度升高,肾组织p-AMPK表达下调,RIPK-1、RIPK-3和MLKL表达上调(P＜0.05),肾组织发生病理学损伤;与AKI组相比,BBR组血清BUN和Cr浓度降低,肾组织p-AMPK表达上调,RIPK-1、RIPK-3和MLKL表达下调(P＜0.05),肾组织病理学损伤减轻;与BBR组相比,BBR-Comp C组血清BUN和Cr浓度升高,肾组织p-AMPK表达下调,RIPK-1、RIPK-3和MLKL表达上调(P＜0.05),肾组织病理学损伤加重.结论 小檗碱可减轻肝移植术大鼠AKI,其机制可能与促进AMPK磷酸化,抑制程序性坏死有关.
Abstract
Objective To evaluate the effect of berberine on acute kidney injury(AKI)in rats un-dergoing liver transplantation and the role of AMP-activated protein kinase(AMPK).Methods Twenty-four SPF-grade adult male Sprague-Dawley rats,aged 12 weeks,weighing 210-230 g,were divided into 4 groups(n=6 each)using the random number table method:sham operation group(S group),AKI group,berberine group(BBR group),and berberine+AMPK inhibitor Compound C group(BBR-Comp C group).In BBR group,berberine 200 mg/kg was given by gavage starting from 2 weeks before surgery,once a day for 14 consecutive days.In BBR-Comp C group,Compound C 1 mg/kg was injected into the tail vein at 30 min before surgery.The rat AKI model was prepared by in situ liver transplantation in AKI group,BBR group and BBR-Comp C group.Blood specimens were taken from the inferior vena cava at 24 h postopera-tively,and serum BUN and Cr concentrations were determined by enzyme-linked immunosorbent assay.Then the rats were sacrificed,and the kidney tissues were taken for microscopic examination of the pathological changes(with the light microscope after HE staining)and for determination of the expression of phosphoryl-ated AMPK(p-AMPK),receptor-interacting protein kinase-1(RIPK-1),receptor-interacting protein ki-nase-3(RIPK-3)and mixed lineage kinase domain-like protein(MLKL)(by Western blot).Results Compared with S group,the serum BUN and Cr concentrations were significantly increased,the p-AMPK expression was down-regulated,the expression of RIPK-1,RIPK-3 and MLKL was up-regulated(P＜0.05),and the pathological damage to renal tissues occurred in AKI group.Compared with AKI group,the serum BUN and Cr concentrations were significantly decreased,the p-AMPK expression was up-regulated,the ex-pression of RIPK-1,RIPK-3 and MLKL was down-regulated(P＜0.05),and the pathological changes of re-nal tissues were significantly attenuated in BBR group.Compared with BBR group,the serum BUN and Cr concentrations were significantly increased,the p-AMPK expression was down-regulated,and the expression of RIPK-1,RIPK-3 and MLKL was up-regulated in BBR-Comp C group(P＜0.05).Conclusions Berber-ine can attenuate AKI in rats undergoing liver transplantation,and the mechanism may be related to the pro-motion of AMPK phosphorylation and inhibition of programmed necrosis.
关键词
小檗碱/肝移植/急性肾损伤/AMP活化蛋白激酶类Key words
Berberine/Liver transplantation/Acute kidney injury/AMP-activated protein kinases引用本文复制引用
基金项目
桂林市技术应用与推广计划(20210227-4)
广西自然科学基金(2022GXNSFAA103012)
广西自然科学基金(2022GXNSFAA103014)
广西壮族自治区医疗卫生重点培育学科建设项目()
Guangxi Medical and Health Key Cultivation Discipline Construction Project()
出版年
2024
NETL
NSTL
万方数据