AT1受体自身抗体对糖尿病肾病大鼠肾脏细胞凋亡及JNK表达的作用

 目的:探讨血管紧张素Ⅱ1型受体自身抗体（angiotensin Ⅱ type 1 receptor autoantibody，AT1-AA）对糖尿病肾病（diabetic nephropathy，DN）大鼠肾脏细胞凋亡及内质网应激（endoplasmic reticulum stress，ERS）相关的JNK表达的作用。方法:高糖高脂饮食联合小剂量链脲佐菌素腹腔注射制备DN大鼠模型，采用ELISA法检测大鼠AT1-AA阳性率，根据检测结果随机选择AT1-AA阳性和AT1-AA阴性大鼠共12只纳入DN组，同时选择6只正常大鼠纳入NC组；TUNEL法检测肾脏细胞凋亡；Western blotting技术测定肾组织ERS标志蛋白葡萄糖调节蛋白78 （GRP78）及凋亡蛋白p-JNK的表达水平。结果:DN组大鼠肾脏细胞凋亡率较NC组显著升高，且AT1-AA阳性大鼠凋亡率明显高于AT1-AA阴性大鼠（P<0.01）。Western blotting结果显示，GRP78和p-JNK蛋白在DN组大鼠肾组织中的水平较NC组显著升高，AT1-AA阳性DN大鼠肾组织中，前述蛋白的改变较AT1-AA阴性DN大鼠更为明显（P<0.05）。结论: AT1-AA可诱导DN大鼠肾脏ERS反应，并通过ERS相关的JNK凋亡途径介导肾脏细胞凋亡，损害肾脏功能。

Effects of AT1 receptor autoantibody on renal cell apoptosis and JNK expression in diabetic nephropathy rats

AIM:To study the effects of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) on the apoptosis of  renal cell and the expression of c-Jun N-terminal kinase (JNK) in diabetic nephropathy (DN) rats. METHODS:High-sucrose and high-fat diet and intraperitoneal injection of streptozotocin were utilized to induce DN rat model. We employed enzyme-linked immunosorbent assay (ELISA) for serum AT1-AA and TUNEL staining for renal cell apoptosis. Furthermore, Western blotting was performed to measure the levels of endoplasmic reticulum stress (ERS) chaperone glucose-regulated protein 78 (GRP78) and ERS-associated apoptosis protein p-JNK. RESULTS:The renal cell apoptotic rate in DN group was significantly increased compared with NC group, and the apoptotic renal cells in AT1-AA positive DN rats were much greater than those in AT1-AA negative DN rats (P<0.05). The protein levels of GRP78 and p-JNK were significantly increased compared with NC group. GRP78 and p-JNK protein levels also significantly increased in AT1-AA positive DN rats compared with AT1-AA negative DN rats. CONCLUSION: AT1-AA activates ERS response and induces renal cell apoptosis via the JNK apoptotic pathway in the renal tissues of DN rats.