| 摘要: |
| 目的 探讨miRNA-455-3p在糖尿病肾病（DKD）大鼠肾小球硬化过程中的作用，以及厄贝沙坦对这一过程的影响。方法 miRNA-455-3p激动剂干预实验：雄性SD大鼠18只，随机取其中6只作为对照组；其余12只大鼠采用高脂高糖饲料喂养及链脲佐菌素（STZ）30 mg/kg腹腔注射制备DKD模型，造模成功后随机分为模型组（STZ组）和过表达miRNA-455-3p组（STZ+miRNA-455-3p组），每组6只，其中STZ+miRNA-455-3p组在STZ注射后第2周和第5周时以20 mg/kg的剂量腹腔注射miRNA-455-3p激动剂。厄贝沙坦干预实验：雄性SD大鼠18只随机分为对照组、模型组（STZ组）、厄贝沙坦干预组（STZ+厄贝沙坦组），每组6只，其中STZ+厄贝沙坦组予以50 mg/kg的厄贝沙坦悬浊液灌胃。所有大鼠均于12周后记录24 h尿量、24 h尿蛋白水平，采用qRT-PCR法检测各组大鼠血清及肾组织中miRNA-455-3p的表达水平，过碘酸希夫染色法观察大鼠肾组织病理改变，蛋白质印迹法检测肾组织中胶原蛋白Ⅰ和增殖细胞核抗原（PCNA）蛋白表达水平。结果 STZ+miRNA-455-3p组及STZ+厄贝沙坦组大鼠24 h尿量、24 h尿蛋白水平均较STZ组降低，差异均有统计学意义（P均<0.05）；STZ+miRNA-455-3p组及STZ+厄贝沙坦组大鼠血清及肾组织中miRNA-455-3p表达水平均较STZ组升高，差异均有统计学意义（P均<0.05）；STZ+miRNA-455-3p组及STZ+厄贝沙坦组大鼠肾组织中胶原蛋白Ⅰ、PCNA表达均较STZ组减少，差异均有统计学意义（P均<0.05）。结论 miRNA-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miRNA-455-3p表达延缓DKD肾小球硬化进程。 |
| 关键词: 糖尿病肾病 miRNA-455-3p 肾小球硬化 厄贝沙坦 |
| DOI：10.16781/j.0258-879x.2021.11.1224 |
| 投稿时间：2021-01-21修订日期：2021-03-04 |
| 基金项目:上海市虹口区卫生健康委员会、科学技术委员会重大医学课题（虹卫1902-03），虹口区"国医强优"三年行动计划区域中医优势专科培育及提升项目（HGY-YSZK-2018-13）. |
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| Role of microRNA-455-3p in glomerulosclerosis of rats with diabetic kidney disease and the effect of irbesartan |
| WU Jian*,ZHU Ming-ying,XU Meng-zhu,LU Kan,SHAO Xiao-hong,ZHU Chun-ling,ZHOU Jing |
(Department of Endocrinology, Shanghai TCM-integrated Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the role of miRNA-455-3p in the process of glomerulosclerosis in rats with diabetic kidney disease (DKD) and the intervention effect of irbesartan. Methods Intervention experiment of miRNA-455-3p agonist:there were 18 male SD rats, 6 of which were randomly selected as normal control group, and the other 12 rats were fed with high-fat and high-sugar diet and intraperitoneally injected with streptozotocin (STZ) to prepare DKD models. After successful modeling, they were randomly divided into model group (STZ group) and overexpression miRNA-455-3p group (STZ+miRNA-455-3p group), with 6 rats in each group. In the STZ+miRNA-455-3p group, miRNA-455-3p agonist was injected intraperitoneally at a dose of 20 mg/kg at the second and fifth weeks after STZ injection. Irbesartan intervention experiment:18 male SD rats were divided into normal control group, model group (STZ group) and irbesartan intervention group (STZ+irbesartan group), with 6 rats in each group. The STZ+irbesartan group was gavaged with 50 mg/kg irbesartan suspension. The 24-h urine volume and 24-h urine protein levels were recorded after 12 weeks. The expression levels of miRNA-455-3p in sera and kidney tissues were detected by qRT-PCR. The pathological changes of rat kidney tissues were observed by periodic acid Schiff staining, and the expression levels of collagenⅠand proliferating cell nuclear antigen (PCNA) were detected by Western blotting. Results The 24-h urine volume and 24-h urine protein levels of rats in the STZ+miRNA-455-3p and STZ+irbesartan groups were significantly lower than those in the STZ groups (all P<0.05); the expression levels of miRNA-455-3p in sera and kidney tissues of rats in the STZ+miRNA-455-3p and STZ+irbesartan groups were significantly higher than those of the STZ groups (all P<0.05); and the expression levels of collagenⅠand PCNA in the kidney tissues of rats in the STZ+miRNA-455-3p and STZ+irbesartan groups were significantly lower than those in the STZ groups. Conclusion miRNA-455-3p participates in the process of DKD and may be a new target for DKD treatment, and irbesartan can delay the process of DKD glomerulosclerosis by regulating miRNA-455-3p. |
| Key words: diabetic nephropathies microRNA-455-3p glomerulosclerosis irbesartan |
