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目的研究糖尿病肾病(diabetic nephropathy,DN)大鼠血清血管紧张素Ⅱ1型受体自身抗体(angiotensinⅡtype 1receptor agonistic autoantibody,AT1-AA)与肾皮质中miRNA-155之间的相关性。方法雄性SD大鼠36只,随机分为正常对照(NC)组和模型组,模型组大鼠给予高糖高脂饮食联合小剂量链脲佐菌素腹腔注射建立DN大鼠模型。模型成功后持续观察12周,应用ELISA技术检测模型组大鼠血清AT1-AA,根据检测结果选择12只纳入DN组,并分为AT1-AA阳性DN(AT1-AA positive DN,APD)和AT1-AA阴性DN(AT1-AA negative DN,AND)2个亚组。实验结束时,检测DN大鼠肾功能生化指标;光镜和电镜观察肾脏病理学特征变化;RT-PCR测定肾组织miRNA-155的表达。结果 DN组大鼠AT1-AA阳性率及OD值均高于NC组大鼠(P<0.001)。DN大鼠肾组织中miRNA-155的表达显著高于NC大鼠(P<0.001),进一步比较发现,AND亚组大鼠miRNA-155表达亦明显高于APD亚组大鼠(P<0.05)。结论 AT1-AA参与了DN大鼠肾脏功能损害过程并且其产生与miRNA-155的表达有关。
Objective To investigate the correlation between serum angiotensin Ⅱ type 1 receptor agonistic autoantibodies (AT1-AA) and miRNA-155 in renal cortex in diabetic nephropathy (DN) rats. Methods Thirty-six male Sprague-Dawley rats were randomly divided into normal control (NC) group and model group. Rats in model group were given high glucose and high fat diet combined with low-dose streptozotocin intraperitoneal injection to establish DN model. After the model was successfully observed for 12 weeks, ELISA method was used to detect serum AT1-AA in model group. Twelve of them were selected into DN group according to the results of the test and divided into AT1-AA positive DN (APD) and AT1 -AA negative DN (AT1-AA negative DN, AND) 2 subgroups. At the end of the experiment, the renal biochemical indexes of DN rats were detected. The changes of renal pathological features were observed under light and electron microscopes. The expression of miRNA-155 in renal tissues was detected by RT-PCR. Results The positive rate and OD value of AT1-AA in DN group were significantly higher than those in NC group (P <0.001). The expression of miRNA-155 in DN rats was significantly higher than that in NC rats (P <0.001). Furthermore, miRNA-155 expression in AND rats was also significantly higher than that in APD rats (P <0.05) . Conclusion AT1-AA participates in the process of renal dysfunction in DN rats and its production is related to the expression of miRNA-155.