狼疮肾炎患者自噬水平及其对足细胞相关蛋白表达水平的影响

    Autophagy in patients with lupus nephritis and its effect on podocyte related protein expression

      摘要
    • 摘要: 目的 探讨狼疮肾炎（lupus nephritis，LN）患者自噬水平及其对足细胞相关蛋白表达水平的影响。方法 选择2017年5月至2019年5月于榆林市第一医院收治的69例LN患者为LN组，50例系统性红斑狼疮（systemic lupus erythematosus，SLE）患者为SLE组，50例肾切除手术患者为对照组，观察3组肾脏足细胞内自噬体数量，比较3组肾脏组织中自噬相关蛋白、微管相关蛋白轻链3（LC3）、B淋巴细胞瘤蛋白质-2-相互作用蛋白（Beclin1）的表达，以及足细胞相关蛋白，肾病蛋白（Nephrin）、足突蛋白（Podocin）的表达。分离狼疮肾炎患者肾脏足细胞，将足细胞分为自噬抑制组和自噬诱导组，自噬抑制组加入100 nmol/L 3-甲基腺嘌呤（3-MA），自噬诱导组加入100 nmol/L雷帕霉素（RAPA），比较3组足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin等蛋白的表达。结果 LN组、SLE组肾脏足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于对照组（P<0.05）；SLE组肾脏足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于LN组（P<0.05）；自噬诱导组足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于正常对照组、自噬抑制组（P<0.05）；正常对照组足细胞内自噬体数量及LC3、Beclin-1、Podocin、Nephrin蛋白表达量显著高于自噬抑制组（P<0.05）。结论 LN患者自噬水平呈升高状态，自噬水平升高可能通过上调足细胞相关蛋白Podocin、Nephrin水平而减轻足细胞损伤，抑制LN病情进展。

       

      Abstract: Objective To investigate the autophagy in patients with lupus nephritis(LN)and its effect on podocyte related protein expression.Methods A total of 69 LN patients(LN group),including 50 cases of systemic lupus erythematosus(SLE group)and 50 patients with nephrectomy(control group)in our hospital from May 2017 to May 2019,were enrolled.Various indexes were compared among groups,including number of autophagosomes in the renal podocytes,the expression of autophagy-related proteins,microtubule-associated protein light chain 3(LC3),Beclin1,podocyte-associated proteins,Nephrin and Podocin.The renal podocytes were isolated from patients with lupus nephritis,and were divided into autophagy inhibition group and autophagy induction group.100 nmol/L 3-methyladenine(3-MA)was added for the autophagy inhibition group,and 100 nmol/L rapamycin(RAPA)was added for the autophagy induction group.The number of autophagosomes in the podocytes and the expression of LC3,Beclin-1,Podocin and Nephrin proteins were compared between groups.Results The number of autophagosomes in the podocytes and the expression of LC3,Beclin-1,Podocin and Nephrin proteins in the LN and SLE groups were significantly higher than those in the control group(P<0.05).The number of autophagosomes in the podocytes and the expression of LC3,Beclin-1,Podocin and Nephrin proteins in the SLE group were significantly higher than those in the LV group(P<0.05).followed by normal control group and autophagy inhibition group(P<0.05).The number of autophagosomes in the podocytes and the expression of LC3,Beclin-1,Podocin and Nephrin proteins in the autophagy induction group were significantly higher than those in the control and autophagy inhibition groups(P<0.05).The number of autophagosomes in the podocytes and the expression of LC3,Beclin-1,Podocin and Nephrin proteins in the control group were significantly higher than those in the autophagy inhibition group(P<0.05).Conclusions The level of autophagy in patients with lupus nephritis is elevated.The increase of autophagy level may reduce podocyte injury and inhibit the progression of lupus nephritis by up-regulating Podocin and Nephrin levels.

       

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