| 詹海婷,古丽尼格尔·艾尔肯,胡振飞,李佳馨,吴建江.基于HIF-1α-iNOS信号通路探讨瑞舒伐他汀联合缺血后处理对糖尿病小鼠的心肌保护作用[J].,2022,(4):610-614 |
| 基于HIF-1α-iNOS信号通路探讨瑞舒伐他汀联合缺血后处理对糖尿病小鼠的心肌保护作用 |
| Based on HIF-1α-iNOS Signaling Pathway in Rosuvastatin Combined with Ischemic Post-Treatment in Protecting Myocardium in Diabetic Rats |
| 投稿时间：2021-07-23 修订日期：2021-08-19 |
| DOI：10.13241/j.cnki.pmb.2022.04.003 |
| 中文关键词: HIF-1α-iNOS信号通路 瑞舒伐他汀 缺血后处理 糖尿病 缺血再灌注损伤 |
| 英文关键词: HIF-1α-iNOS signaling pathway Rosuvastatin Ischemic post-treatment Diabetic Ischemia-reperfusion injury |
| 基金项目:新疆维吾尔自治区自然科学基金项目（2019D01C293） |
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| 中文摘要: |
| 摘要 目的：探讨瑞舒伐他汀联合缺血后处理对糖尿病小鼠心肌的作用并分析其保护作用的机制。方法：应用高脂高糖饮食的方法构建2型糖尿病小鼠动物模型，随机分为假手术组（sham组）、缺血/再灌注组(I/R组)、缺血后处理组（IpostC组）及瑞舒伐他汀联合缺血后处理组（RPO+IpostC组），每组10只。分析各组小鼠低氧诱导因子-1α（HIF-1α）、诱导型一氧化氮合酶（iNOS）蛋白表达及血浆炎症因子、血清一氧化氮（NO）水平变化，观察各组小鼠心肌梗死面积、心肌组织HE染色结构变化。结果：与I/R组、IPostC组相比，RPO+IpostC组HIF-1α，iNOS蛋白表达显著上调（P<0.05）；与IpostC 组相比，RPO+ IpostC组小鼠血清NO和血浆IL-1β、IL-6、TNF-α水平均明显降低，血浆IL-10升高（P<0.05）；经显微镜观察显示，sham组小鼠的心肌细胞HE染色结构正常，RPO+IpostC组小鼠心肌细胞HE染色后损伤相对较小；与I/R组相比，IpostC组和RPO+IpostC组小鼠缺血面积（AAR/LV）、梗死面积（IRR/AAR）均明显减小，且RPO+IpostC组小鼠AAR/LV、IRR/AAR最小（P<0.05）。结论：瑞舒伐他汀联合缺血后处理可以通过对糖尿病小鼠HIF-1α-iNOS信号通路进行调节，进而上调HIF-1α、iNOS蛋白表达，减轻炎症反应，降低心肌细胞缺血再灌注损伤，保护心肌。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the protective effect of rosuvastatin combined with ischemic post-treatment in protecting myocardium in diabetic rats and analyze its protective mechanism. Methods: The rats animal model of type 2 diabetes mellitus was constructed by high fat and high sugar diet, and they were randomly divided into sham operation group (sham group), ischemia/reperfusion group (I/R group), ischemic post-treatment group (IpostC group) and rosuvastatin combined with ischemic post-treatment group (RPO+IpostC group), with 10 rats in each group. The expressions of hypoxia-inducible factor-1 α (HIF-1α) and inducible nitric oxide synthase (iNOS) protein, the levels of plasma inflammatory factors and serum nitric oxide (NO) in each group were analyzed, and the changes of myocardial infarction size and HE staining structure in myocardial tissue were observed in each group. Results: Compared with I/R group and IPostC group, the expression of HIF-1α and iNOS protein in RPO+ IPostC group were significantly up-regulated (P<0.05). Compared with IpostC group, the levels of serum NO and plasma IL-1β, IL-6 and TNF-α in RPO+ IpostC group were significantly decreased, while plasma IL-10 was increased (P<0.05). Microscopic observation showed that the myocardial cells in the sham group had normal HE staining structure, while the myocardial cells in the RPO+IpostC group had relatively little damage after HE staining. Compared with I/R group, ischemic area (AAR/LV), infarct area (IRR/AAR) of rats in IpostC group and RPO+IpostC group were significantly decreased, and AAR/LV and IRR/AAR in RPO+IpostC group were the least (P<0.05). Conclusion: Rosuvastatin combined with ischemic post-treatment can regulate the HIF-1α-iNOS signaling pathway in diabetic rats, raise the expression of HIF-1α and iNOS protein, alleviating inflammatory response, reducing myocardial ischemia-reperfusion injury, and protecting myocardium. |
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