糖尿病肾病大鼠血管紧张素Ⅱ1型受体自身抗体与肾脏损伤和细胞凋亡的关系∗

摘要

Objective:To explore the relationship between angiotensin Ⅱtype 1 receptor autoantibody (AT1-AA)and kidney tissue pathologic changes,and apoptosis of renal tubular epithelial cells and podocytesin diabetic ne-phropathy (DN)rats.Method:36 SD rats were randomly divided into normal control group (NC,n = 6)and DN model group (DN,n=30).DN model rats were induced by high-sucrose and high-fat diet and intraperitoneal injec-tion of a small dose of streptozotocin (STZ,35mg/kg).ELISA method was used to test the levels of serum AT1-AA,and respectively divided into AT1-AA positive and negative subgroups according to the ELISA results.The blood glucose (BG),renal function indicators and kidney hypertrophy index (KW/BW)were detected and calculat-ed.HE staining and transmission electron microscope were applied to detect renal tubular and glomerulus pathologi-cal changes in all group rats.The apoptosis of renal tubular epithelial cells and podocytes were detected by TUNEL staining.Results:The level and positive rate of AT1-AA in DN group were significantly higher than that in NC group (P <0.01and P <0.05).When compared with NC group,the level of BG,rest of renal function indicators and the ratio of KW/BW in AT1-AA positive DN group were significantly increased,with the creatinine clearance rate (Ccr)decreased (all P <0.01).The levels of all the indicators above except BG in AT1-AA negative DN group were significantly reduced (P <0.05 or P <0.01)compared with AT1-AA positive DN group.Comparing with NC group,the kidney and ultrastructure had pathological changes in AT1-AA positive DN group,the apoptosis rate of renal tubular epithelial cells and glomerular podocytes also increased significantly (P < 0.01 ).While no obvious pathological changes were observed in the kidney of AT1-AA negative DN rats,and the cell apoptosis rate of AT1-AA negative DN group were obviously lower than that of AT1-AA positive DN group.Conclusion:These findings indicate that the AT1-AA levels may be related to the apoptosis of renal tubular epithelial cells and glomerular podo-cytes,and involved in the process of kidney damage.%目的：：探讨糖尿病肾病(DN)大鼠血管紧张素Ⅱ1型受体自身抗体(AT1-AA)与肾脏组织病理变化和肾小管上皮细胞及肾小球足细胞凋亡的关系。方法：36只雄性 SD 大鼠,随机分为正常对照组(NC 组,n=6)和 DN模型组(DN 组,n=30),DN 组大鼠给予高糖高脂喂养联合小剂量(35mg/kg)链脲佐菌素(STZ)腹腔注射建立 DN模型。应用 ELISA 检测各组大鼠血清 AT1-AA 水平,并据此将各组再分为 AT1-AA 阳性和阴性亚组,检测各组大鼠血糖(BG)、肾功能指标及肾脏肥大指数(KW/BW)；采用 HE 染色和透射电镜观察各组大鼠肾小管和肾小球病理变化；采用 TUNEL 法检测肾小管上皮细胞和肾小球足细胞凋亡。结果：DN 组大鼠 AT1-AA 水平和阳性率明显高于 NC 组(P <0.05或 P <0.01)。与 NC 组比较,AT1-AA 阳性 DN 大鼠肌酐清除率(Ccr)显著降低,BG、肾功能指标及 KW/BW 明显升高(均 P <0.01)；AT1-AA 阴性 DN 大鼠除 BG 和 KW/BW 外,其它指标与 AT1-AA阳性 DN 大鼠差异均有统计学意义(P <0.05或 P <0.01)。与 NC 组比较,AT1-AA 阳性 DN 大鼠均出现肾组织及超微结构病理变化,肾小管上皮细胞和肾小球足细胞凋亡率亦显著升高(P <0.01)；AT1-AA 阴性 DN 大鼠肾脏未见明显病变,细胞凋亡率显著低于 AT1-AA 阳性 DN 大鼠(P <0.05)。结论：AT1-AA 水平变化与 DN 大鼠肾小管上皮细胞和肾小球足细胞凋亡有关,可能通过介导细胞凋亡而参与肾脏损害过程。