汉黄芩苷对IgA肾病大鼠NF-κB/NLRP3通路及系膜增生的影响

Effects of baicalin on NF-κB/NLRP3 signaling pathway and mesangial proliferation in rats with IgA nephropathy

目的:探讨汉黄芩苷(wogonoside,WG)对免疫球蛋白A肾病(immunoglobulin A nephropathy,IgAN)大鼠系膜增生及核因子-kappa B(nuclear factor-kappa B,NF-κB)/核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)通路的影响。方法:牛血清白蛋白灌胃联合四氯化碳与脂多糖注射建立IgAN大鼠模型。模型成功后随机分为模型组、WG(低、中、高)剂量组、地塞米松组,每组8只;另设对照组。检测血清肌酐(serum creatinine,SCr)、血尿素氮(blood urea nitrogen,BUN)水平,24 h尿蛋白(24 hour urinary protein,24-UTP)和24 h尿红细胞数,肾脏组织形态,肾脏组织中NF-κB、NLRP3、接头蛋白ASC(apoptosis-associated speck-like proteincontain a caspase activation and recruitment domain,ASC)、半胱氨酸天冬氨酸蛋白酶酶原(cysteine-containing aspartate-specific-3 proteases,pro-caspase-1)、血清中白介素(interleukin,IL)-1β、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。结果:与对照组相比,模型组肾小球系膜及基质细胞增生严重、炎症明显、荧光聚集,SCr、BUN、24-UTP水平、24 h尿红细胞数、肾脏组织中核内NF-κB、核内NF-κB/总NF-κB、NLRP3、ASC、pro-caspase-1、caspase-1蛋白、血清中IL-1β、TNF-α水平升高(P<0.05);肾脏组织中核外NF-κB蛋白水平降低(P<0.05)。与模型组相比,WG剂量组肾小球系膜及基质细胞增生减弱,荧光强度减弱,肾脏组织中核外NF-κB蛋白水平升高(P<0.05),SCr、BUN、24-UTP水平、24 h尿红细胞数、肾脏组织中核内NF-κB、核内NF-κB/总NF-κB、NLRP3、ASC、pro-caspase-1、caspase-1蛋白、血清中IL-1β、TNF-α水平降低(P<0.05),呈剂量依赖效应。结论:WG可抑制NF-κB/NLRP3通路实现对IgAN系膜增生的缓解。

Objective:To investigate the effects of wogonide(WG)on mesangial proliferation and nuclear factor kappa B(NF-κB)/nucleotide binding oligomerization domain like receptor protein 3(NLRP3)pathway in rats with immunoglobulin A nephropathy(IgAN).Methods:IgAN rat model was established by gavage of bovine serum albumin combined with carbon tetrachloride and lipopolysaccharide injection.After the establishment of the model,they were randomly divided into model group,WG(low,medium,high)dose group and dexamethasone group,with 8 rats in each group,and the control group was set up.Serum creatinine(SCr),blood urea nitrogen(BUN),24 hour urinary protein(24-UTP),24 hour urinary red blood cells,renal tissue morphology,NF-κB,NLRP3,ASC(aspartate containing aspartate specific-3)in kidney tissue were detected,the levels of pro-caspase-1,IL-1βand TNF-αin serum were measured.Results:Compared with the control group,glomerular mesangium and stromal cells heavily proliferated,inflammation was obvious,fluorescence gathered in the model group,while the level of SCr,BUN,24-UTP,24 hour the number of urinary red blood cells,nuclear NF-κB,nuclear/total NF-κB,NLRP3,ASC,pro-caspase-1,caspase-1 protein,serum IL-1β,TNF-αlevels in the model group were increased(P<0.05),and the level of extranuclear NF-κB protein in kidney tissue was decreased(P<0.05).Compared with the model group,glomerular mesenteric and stromal cells proliferation decreased,fluorescence intensity decreased in WG dose group(P<0.05),the level of extranuclear NF-κB protein in kidney tissue increased,while the level of SCr,BUN,24-UTP,24 hour the number of urinary red blood cells,nuclear NF-κB,nuclear/total NF-κB,NLRP3,ASC,pro-caspase-1,caspase-1 protein,IL-1βand TNF-αin serum were decreased(P<0.05),and in a dose-dependent manner.Conclusions:WG can inhibit NF-κB/NLRP3 pathway and alleviate IgAN mesangial hyperplasia.