特发性膜性肾病30例肾小管上皮细胞自噬改变及其临床意义  

Changes of autophagy in renal tubular epithelial cells in patients with idiopathic membranous nephropathy and its clinical significance

作　　者：周冰倩 崔诗淇 李钗 耿舰[2] 李德天[1] 周华[1] 苏雪松[1] 杜丰[1] 王艳秋[1] ZHOU Bing-qian;CUI Shi-qi;LI Chai;GENG Jian;LI De-tian;ZHOU Hua;SU Xue-song;DU Feng;WANG Yan-qiu(Department of Nephrology,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院肾内科,辽宁沈阳110004 [2]南方医科大学,广东广州510515

出　　处：《中国实用内科杂志》2018年第12期1160-1164,共5页Chinese Journal of Practical Internal Medicine

基　　金：辽宁省社会发展攻关计划(2013225049);辽宁省教育厅科学研究一般项目(L2014313)

摘　　要：目的观察特发性膜性肾病(idiopathic membranous nephropathy,IMN)患者肾小管自噬体数量、自噬相关蛋白Beclin-1和LC3的表达,了解肾小管上皮细胞自噬是否参与了IMN肾间质纤维化的进展。方法回顾性总结2015年6月至2016年12月在中国医科大学附属盛京医院经肾活检确诊为IMN患者30例,在透射电子显微镜下观察IMN患者肾组织肾小管上皮细胞自噬体的数量,免疫组化检测自噬相关蛋白Beclin-1和LC3的表达,分析其与24 h尿蛋白定量、肾间质纤维化程度及肾功能等临床相关指标的相关性。结果与正常肾组织相比,IMN组的肾小管上皮细胞自噬体数量、自噬相关蛋白Beclin-1和LC3表达显著增加(t=-13.266,P<0.001;t=-5.261,P<0.001;t=-2.394,P=0.026);在IMN组中,与无纤维化组相比,有纤维化组自噬小体数量、Beclin1和LC3表达均显著增加(t=-6.04,P<0.001;t=-2.795,P=0.014;t=-2.761,P=0.004);在IMN患者中,自噬小体数量、Beclin1和LC3均与患者肾间质纤维化累及面积成正相关(r分别为0.757、0.658和0.638,均P<0.001);LC3与24 h尿蛋白定量成负相关(r=-0.463,P=0.01),Beclin1与血清尿素氮(BUN)成正相关(r=0.433,P=0.017),自噬小体数量与患者性别具有一定的相关性(r=-0.472,P=0.008)。结论在IMN患者中,肾小管上皮细胞自噬参与了肾间质纤维化的进展。Objective To observe the changes in the number of tubular autophagosomes and the expression of autophagy-related proteins Beclin-1 and LC3 in patients with idiopathic membranous nephropathy(IMN) and to further understand whether autophagy in renal tubular epithelial cells is involved in IMN progression.Methods Retrospective review of 30 cases of IMN diagnosed by renal biopsy at Shengjing Hospital affiliated to China Medical University from June 2015 to December 2016.The number of autophagosomes in renal tubular epithelial cells was observed by transmission electron microscopy.The expression of autophagy-related proteins Beclin-1 and LC3 in renal tubular epithelial cells was detected by immunohistochemistry.The correlation of the expression of autophagy and 24 hour urinary protein quantification,renal interstitial fibrosis degree,the clinical indications of renal function.Results(1) Compared with normal renal tissues,the number of autophagosomes and the expression of autophagy-related proteins Beclin-1 and LC3 were significantly increased in IMN group(t=-13.266,P<0.001;t=-5.261,P<0.001;t=-2.394,P=0.026);in the IMN group,there was a significant increase in the number of autophagosomes,and the Beclin1 and LC3 expression in the fibrotic group,compared with the nonfibrotic group(t=-6.04,P<0.001;t=-2.795,P=0.014;t=-2.761,P=0.004);(2) In the IMN group,the number of autophagosomes and expression of Beclin1 and LC3 were positively correlated with the degree of renal interstitial fibrosis(r=0.757,0.658,0.638,P<0.001);LC3 was negatively correlated with 24-hour urine protein quantitation(r=-0.463,P=0.01),Beclin1 and serum urea nitrogen(BUN) was positively correlated(r=0.433,P=0.017),and there was a correlation between the number of autophagosomes and the sex of the patients(r=-0.472,P=0.008).Conclusion Autophagy in renal tubular epithelial cells is involved in the progression of renal interstitial fibrosis in IMN.

关 键 词：膜性肾病 纤维化 自噬 

分 类 号：R692[医药卫生—泌尿科学]