miR-455-3p在糖尿病肾脏疾病大鼠肾小球硬化过程中的作用及厄贝沙坦的干预研究

目的：研究miR-455-3p在糖尿病肾脏疾病（Diabetic kidney disease, DKD）大鼠肾小球硬化过程中的作用，以及厄贝沙坦的干预对miR-455-3p及肾小球硬化过程的影响。方法：取雄性SD大鼠24只，随机取6只作为正常组（Control组），余大鼠采用高脂高糖饲料喂养及链脲佐菌素（STZ）腹腔注射制备DKD模型，造模成功后随机分为模型组（STZ组）、过表达miR-455-3p组（STZ+miR-455-3p组）、厄贝沙坦干预组（STZ+厄贝沙坦组）。其中，STZ+miR-455-3p组在STZ注射后第二周和第五周以20mg/kg的剂量腹腔注射miR-455-3p 激动剂（miR-455-3p agomir），STZ+厄贝沙坦组予50mg/kg的厄贝沙坦悬浊液灌胃，其他组予等剂量生理盐水灌胃，12周后记录大鼠24h尿量、24h尿白蛋白水平，采用qRT-PCR法检测各组大鼠血清及肾组织中miR-455-3p的表达水平，PAS染色法观察大鼠肾组织病理改变，Western blot方法检测肾组织中胶原蛋白I（Collagen I）和增殖细胞核抗原（Proliferating Cell Nuclear Antigen ,PCNA）蛋白表达水平。结果：（1）STZ+miR-455-3p及STZ+厄贝沙坦组大鼠24h尿量、24h尿白蛋白水平较之STZ组明显降低，差异具有统计学意义（P<0.05）；（2）STZ+miR-455-3p及STZ+厄贝沙坦组大鼠血清及肾组织中miR-455-3p表达水平较之STZ组明显升高，差异具有统计学意义（P<0.05）；（3）STZ+miR-455-3p及STZ+厄贝沙坦组大鼠肾组织中Collagen I、PCNA表达水平较STZ组明显减少。结论：miR-455-3p参与DKD进程，可能是DKD治疗的新靶点，而厄贝沙坦能够通过调控miR-455-3p延缓DKD肾小球硬化进程。

The Role of miR-455-3p in the Process of Glomerular Sclerosis in DKD Rats and the Intervention of Irbesartan

To study the role of miR-455-3p in the process of glomerular sclerosis in DKD Rats and the intervention effect of Irbesartan. Methods: Twenty-four SD male rats were taken, and 6 were randomly selected as the normal group (Control group). The remaining rats were fed with high-fat and high-sugar feed and intraperitoneally injected with streptozotocin (STZ) to prepare diabetic kidney disease models. After success, they were randomly divided into model group (STZ group), overexpression miR-455-3p group (STZ+miR-455-3p) and STZ+ Irbesartan group each group Contained six rats. In the STZ+miR-455-3p group, the miR-455-3p agonist (miR-455-3p agomir) was injected intraperitoneally at a dose of 20 mg/kg in the second and fifth weeks after STZ injection. The STZ+irbesartan group was given 50mg/kg irbesartan suspension by gavage, and the other groups were given the same dose of normal saline for 12 weeks. 24h urine volume, and 24h urine albumin levels were recorded in rats. The rats were detected by qRT-PCR method. The expression level of miR-455-3p in rat serum and kidney tissue, PAS staining method to observe the pathological changes of rat kidney tissue, Western blot method to detect the protein expression level of collagen I (Collagen I) and proliferating cell nuclear antigen (PCNA) in kidney. Results: (1) The 24h urine volume, and 24h urine albumin levels of rats after overexpression of miR-455-3p and the intervention of Irbesartan, were significantly lower than those in the STZ group, and the difference was statistically significant (P<0.05). (2) The expression level of miR-455-3p in serum and kidney of rats after the intervention of overexpression miR-455-3p group and Irbesartan, group was significantly higher than that of STZ group, and the difference was statistically significant (P< 0.05); (3) The expression levels of Collagen I and PCNA in the kidney tissue of rats in the STZ+miR-455-3p and STZ+ Irbesartan groups were significantly lower than those in the STZ group. Conclusion: miR-455-3p is involved in the process of glomerular sclerosis in rats with diabetic kidney disease, and may be a new target for DKD therapy, and irbesartan can regulate this process through miR-455-3p.