苦豆子调节JNK信号通路对抗GBM肾炎大鼠的作用研究

Effect of Kudouzi on JNK Signaling Pathway Against GBM Nephritis in Rats

目的:研究苦豆子对抗肾小球基底膜(glomerular basement membrane,GBM)肾炎大鼠的作用及机制研究。方法:30只健康雄性大鼠,随机分为5组,每组6只,分别为对照组、模型组、苦豆子低、中、高剂量组,除对照组外,其余各组采用尾静脉注射给予大鼠兔抗大鼠GBM血清的方法建立大鼠抗GBM肾炎模型,然后根据大鼠体重按照1 g/kg、2 g/kg、4 g/kg灌胃给予大鼠苦豆子提取物,对照组及模型组灌胃给予等量生理盐水,1次/d,连续给药21 d,并于给药第14天和21天测定各组大鼠24 h尿量及尿蛋白量,给药结束后,测定大鼠血浆TNF-α、IL-6及IL-1β水平,血清尿素氮及血肌酐水平,苏木精-伊红染色法对大鼠肾脏进行组织病理学观察,western blot检测大鼠肾脏组织JNK、p-JNK水平,实时定量PCR检测各组大鼠肾脏组织中c-Jun及AP-1 mRNA水平。结果:与模型组比较,苦豆子各剂量组大鼠24 h尿量显著增加(P<0.05),24 h尿蛋白量、血清尿素氮、血肌酐水平、血清尿素氮水平、血肌酐水平及其血浆TNF-α、IL-6及IL-1β水平、肾组织JNK及p-JNK水平、c-Jun及AP-1 mRNA水平均显著降低(P<0.05),大鼠肾组织病理学明显改善。结论:苦豆子能够改善抗GBM肾炎大鼠的疾病状态,其作用机制可能与调节抗GBM肾炎大鼠体内JNK信号通路有关。

Objective:To study the effect and mechanism of Sophora alopecuroides on glomerular basement membrane(glomerular basement membrane,GBM)glomerulonephritis in rats.Methods:Thirty healthy male rats were randomly divided into 5 groups,6 rats in each group,which were control group,model group,low,middle and high dose groups,except the control group.The rat model of anti-GBM nephritis was established by tail vein injection of rabbit anti-GBM serum,and then the water-soluble Sophora alopecuroides extract was given intragastrically according to the body weight of 1 g/kg,2 g/kg and 4 g/kg.The rats in the control group and the model group were given the same amount of normal saline once a day for 21 days,and the 24-hour urine volume and urine protein volume were measured on the 14 th and 21 st day after administration.The levels of plasma TNF-α,IL-6 and IL-1β,serum urea nitrogen and serum creatinine were measured.The histopathology of rat kidney was observed by hematoxylin-eosin staining.The levels of JNK and p-JNK in rat kidney tissue were detected by,western blot.The levels of c-Jun and AP-1 mRNA in renal tissues of rats in each group were detected by real-time quantitative PCR.Results:Compared with the model group,24-hour urine volume was significantly increased,24-hour urine protein,serum urea nitrogen,serum creatinine,serum urea nitrogen,serum creatinine,plasma TNF-α,IL-6 and IL-1βlevels,renal tissue JNK and p-JNK levels,c-Jun and AP-1 mRNA levels were significantly decreased in Kudouzi groups,and renal histopathology was significantly improved.Conclusion:In conclusion,Sophora alopecuroides can improve the disease status of rats with anti-GBM nephritis,and its mechanism may be related to the regulation of JNK signaling pathway in rats with anti-GBM glomerulonephritis.