二氢槲皮素对IgA肾病大鼠肾脏保护的机制  

The renal protective mechanism of dihydroquercetin in rats with IgA nephropathy and the effect on PI3K/Akt signaling pathway

作　　者：师旭辉 于建军 秦洋 曲矿云[1] 刘风勋 SHI Xuhui;YU Jianjun;QIN Yang;QU Kuangyun;LIU Fengxun(Department of Nephrology,Sanmenxia Hospital of Yellow River,Sanmenxia 472000,China;Department of Nephrology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]黄河三门峡医院肾脏内科,三门峡472000 [2]郑州大学第一附属医院肾内科,郑州450000

出　　处：《西北药学杂志》2022年第5期34-39,共6页Northwest Pharmaceutical Journal

基　　金：2019年度河南省医学科技攻关计划联合共建项目(编号:LHGJ20190247)。

摘　　要：目的探讨二氢槲皮素(dihydroquercetin,DHQ)对IgA肾病(IgA nephropathy,IgAN)大鼠肾脏的保护作用及对磷脂酰肌醇-3激酶(phosphatidylinositide 3-kinase,PI3K)/丝氨酸-苏氨酸蛋白激酶(protein kinase B,Akt)信号通路的影响。方法将78只SPF级SD大鼠进行适应性喂养,除对照组(15只)外,取63只建立IgAN大鼠模型,成功造模58只,随机分为模型组(14只)、740 Y-P组(14只)、DHQ组(15只)、740 Y-P+DHQ组(15只),进行相应干预后,于12周后检测各组大鼠炎性因子[肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-1β(interleukin-1β,IL-1β)及白介素-6(interleukin-6,IL-6)]、肾功能[24 h尿蛋白定量(24 hours urinary protein quantitative,24 h pro)、血清肌酐(serum creatinine,Scr)及血尿素氮(blood urea nitrogen,BUN)]水平;HE染色观察肾组织病理变化;Masson染色观察肾纤维化;直接免疫荧光染色观察IgA绿色荧光沉积;Western blot检测Akt、p-Akt、PI3K及p-PI3K蛋白的表达水平。结果DHQ可降低血清TNF-α、IL-1β和IL-6炎性因子以及24 h pro、Scr和BUN的水平,减轻肾组织病理变化,减少大鼠胶原纤维与IgA沉积,降低p-Akt及p-PI3K蛋白的表达水平,以促进肾功能的恢复。结论DHQ可降低IgAN大鼠炎性因子的表达水平,改善胶原蛋白与IgA沉积,减轻病理损害以促进肾功能恢复,其机制可能与抑制PI3K/Akt通路及降低相关蛋白的表达水平有关。Objective To explore the protective effect of dihydroquercetin(DHQ)in IgA nephropathy(IgAN)rats and the effect on phosphatidylinositide 3-kinase(PI3K)/sprotein kinase B(Akt)signaling pathway.Methods 78 SPF SD rats were adaptively fed.In addition to the control group(15 rats),63 IgAN rats were selected to establish the IgAN rat model.58 rats were successfully modeled,and were randomly divided into a model group(14 rats),740 Y-P group(14 rats),DHQ group(15 rats),740 Y-P+DHQ group(15 rats).After corresponding intervention,the inflammatory factor[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)],renal function[24 hours urinary protein quantitation(24 h pro),serum creatinine(Scr),blood urea nitrogen(BUN)]levels in each group were detected 12 weeks later.The pathological changes of kidney tissue were observed by HE staining.The renal fibrosis was observed by Masson staining.The green fluorescence deposition of IgA was observed by direct immunofluorescence staining.The protein expression of Akt,p-Akt,PI3K,and p-PI3K was observed by Western blot method.Results DHQ can reduce the serum TNF-α,IL-1β,IL-6 inflammatory factors and 24 h pro,Scr,BUN levels,reduce the pathological changes in kidney tissue,reduce the deposition of collagen fibers and IgA sedimentation,and reduce the p-Akt and p-PI3K protein expression level to promote the recovery of renal function.Conclusion DHQ can reduce the expression of inflammatory factors in IgAN rats,improve the collagen protein and IgA sedimentation,reduce the pathological damage and promote the recovery of renal function.The mechanism may be related to inhibiting the PI3K/Akt pathway and reducing the expression of related proteins.

关 键 词：二氢槲皮素 IGA肾病 炎性因子 肾功能 IGA沉积 PI3K/AKT信号通路 

分 类 号：R965[医药卫生—药理学] R285.5[医药卫生—药学]