小檗碱激活AMPK/NF-κB/TNF-α信号通路对肾病综合征大鼠肾损伤的影响  

Effect of Berberine Activating of AMPK/NF-κB/TNF-α Signaling Pathway on Kidney Injury in Rats with Nephrotic Syndrome

作　　者：陈汉文 李吉镇 王娜[1] 董国霞[1] 刘雷[1] CHEN Hanwen;LI Jizhen;WANG Na(Affiliated Hospital of Jining Medical University,Jining,272000)

机构地区：[1]济宁医学院附属医院全科医学科,济宁272000 [2]济宁市汶上县人民医院,汶上272500

出　　处：《中国中西医结合肾病杂志》2023年第1期12-16,I0001,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：济宁医学院教师科研扶持基金资助项目(No.JYFC2019FKJ108);济宁市重点研发计划项目(No.2020YXNS028)。

摘　　要：目的:从5’-单磷酸腺苷活化蛋白激酶(AMPK)/核转录因子-κB(NF-κB)/肿瘤坏死因子-α(TNF-α)信号通路,探究小檗碱改善肾病综合征(NS)大鼠肾损伤的可能机制。方法:尾静脉注射阿霉素建立NS大鼠模型,随机分为模型组、小檗碱治疗组、激素治疗组、AMPK抑制剂组、小檗碱+AMPK抑制剂组,每组15只,另取15只对照组大鼠。各组连续给药治疗5周后,收集尿液检测24 h尿蛋白;取动脉血检测血浆白蛋白、血脂水平;PAS染色观察肾组织形态变化;Western blot法检测肾组织AMPK、p-AMPK、NF-κB、p-NF-κB、TNF-α、白细胞介素-6(IL-6)、脂肪酸移位酶(FAT/CD36)、P糖蛋白(P-gp)表达水平。结果:与对照组相比,模型组大鼠肾小球血管袢与球囊壁黏连、肾小管管腔狭窄、肾小管上皮细胞水肿、坏死及空泡化等病理损伤严重,24 h尿蛋白、血脂水平升高,血浆白蛋白含量、AMPK活性、与AMPK有关的炎性反应蛋白及促脂质吸收相关蛋白表达降低(P<0.05)。小檗碱治疗或激素治疗,均可改善NS大鼠肾脏损伤,降低24 h尿蛋白、血脂水平,升高血浆中白蛋白含量,促进AMPK活化,发挥抗炎及改善脂质代谢作用(P<0.05),激素治疗组可引起P-gp表达升高,且其对NS大鼠的治疗效果弱于小檗碱治疗组(P<0.05)。AMPK抑制剂可加重NS大鼠肾损伤,并削弱小檗碱促进AMPK活化、改善NS大鼠肾损伤等作用(P<0.05)。结论:小檗碱可通过促进AMPK活化,改善NS大鼠糖脂代谢、抑制NF-κB/TNF-α炎症通路,发挥肾保护作用。Objective:From the 5′-adenosine monophosphate activated protein kinase(AMPK)/nuclear transcription factor-κB(NF-κB)/tumor necrosis factor-α(TNF-α)signaling pathway,to explore the possible mechanism of berberine in improving kidney injury in rats with nephrotic syndrome(NS).Methods:NS rat models were established by tail vein injection of doxorubicin,and they were randomly divided into model group,berberine treatment group,hormone treatment group,AMPK inhibitor group,and berberine+AMPK inhibitor group,with 15 rats in each group,and another 15 healthy control rats were taken.After 5 weeks of continuous treatment in each group,urine was collected for 24-hour urine protein detection;arterial blood was taken to detect plasma albumin and blood lipid levels;PAS staining was used to observe the morphological changes of kidney tissue;Western blot method was used to detect the expression levels of AMPK,p-AMPK,NF-κB,p-NF-κB,TNF-α,interleukin-6(IL-6),fatty acid translocase(FAT/CD36),and P glycoprotein(P-gp)in kidney tissue.Results:Compared with the control group,the rats in the model group had serious pathological damages such as glomerular vascular loop adhesion to the balloon wall,renal tubular lumen stenosis,renal tubular epithelial cell edema,necrosis,and vacuolation,the 24 h urine protein and blood lipid levels increased,the plasma albumin content,AMPK activity,AMPK-related inflammatory response protein and lipid absorption-promoting protein expression decreased(P<0.05).Both berberine treatment or hormone treatment could ameliorate kidney injury in NS rats,reduce 24-hour urine protein and blood lipid levels,increase the content of albumin in plasma,promote AMPK activation,exert anti-inflammatory effect,and improve lipid metabolism effects(P<0.05),the hormone treatment group could cause the increase of P-gp expression,and its therapeutic effect on NS rats was weaker than that of the berberine treatment group(P<0.05).AMPK inhibitors could aggravate kidney injury in NS rats,and weaken the effects of berberine in pr

关 键 词：小檗碱 肾病综合征 AMPK NF-ΚB TNF-Α 

分 类 号：R285.5[医药卫生—中药学]