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目的探讨AT1受体自身抗体(AT1-AA)对DN大鼠肾脏内质网应激(ERS)通路相关分子葡萄糖调节蛋白78(GRP78)和CCAAT/增强子结合蛋白同源蛋白(CHOP)表达的影响。方法制备DN大鼠模型,ELISA检测血清AT1-AA,根据ELISA结果随机选择AT1-AA阳性和阴性DN大鼠纳入DN组(n=12),同时设立正常对照组(NC,n=6)。电镜观察肾脏超微结构变化;TUNEL法检测肾脏细胞凋亡;RT-PCR测定大鼠肾组织GRP78和CHOP mRNA水平;Western blot分析肾组织中GRP78和CHOP蛋白的表达量。结果 DN组肾脏细胞凋亡率较NC组升高,其中,AT1-AA阳性大鼠凋亡率高于AT1-AA阴性大鼠[(20.05±1.71)%vs(13.24±4.93)%](P<0.01)。与NC组相比,DN组肾组织GRP78、CHOP蛋白和mRNA水平均上调;进一步比较发现,AT1-AA阳性DN大鼠GRP78,CHOP蛋白及mRNA水平升高较AT1-AA阴性DN大鼠更明显。结论 AT1-AA可能通过诱导DN大鼠肾脏ERS反应,并经ERS相关的CHOP凋亡信号通路而促进肾脏细胞凋亡,加重肾脏损害。
Objective To investigate the effect of AT1 receptor autoantibodies (AT1-AA) on the expression of glucose regulated protein 78 (GRP78) and CCAAT / enhancer binding protein (CHOP) proteins in renal endoplasmic reticulum stress (ERS) influences. Methods The rat model of DN was established. Serum AT1-AA was detected by ELISA. AT1-AA-positive and -negative DN rats were randomly assigned to DN group (n = 12) according to the ELISA results and normal control group (NC, n = 6). The changes of renal ultrastructure were observed with electron microscope. The apoptosis of renal cells was detected by TUNEL method. The levels of GRP78 and CHOP mRNA were detected by RT-PCR. The expression of GRP78 and CHOP protein in renal tissues was detected by Western blot. Results The apoptosis rate of renal cells in DN group was higher than that in NC group, and the apoptotic rate in AT1-AA positive rats was higher than that in AT1-AA negative rats [(20.05 ± 1.71)% vs (13.24 ± 4.93)%] <0.01). Compared with NC group, the levels of GRP78, CHOP protein and mRNA in renal tissue of DN group were up-regulated. Furthermore, the levels of GRP78, CHOP protein and mRNA in AT1-AA positive DN rats were higher than those in AT1-AA negative DN rats . Conclusion AT1-AA may promote renal cell apoptosis and induce renal damage through ERS-induced ERS-induced ERS-related CHOP apoptosis signaling pathway.