辛伐他汀对糖尿病大鼠肾脏的保护作用及其可能机制

doi:10.12047/j.cjap.5636.2018.072

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (4): 313-317.doi: 10.12047/j.cjap.5636.2018.072

辛伐他汀对糖尿病大鼠肾脏的保护作用及其可能机制

宛欣¹, 王茜¹, 李凡璐¹, 吴亚俐¹, 刘鑫¹, 陈还珍², 杨静³, 崔香丽¹

1. 山西医科大学基础医学院生理系, 太原 030001;
2. 山西医科大学第一医院心血管内科, 太原 030001;
3. 山西医科大学第一医院内分泌科, 太原 030001

收稿日期:2017-09-25 修回日期:2018-02-28 出版日期:2018-07-28 发布日期:2019-02-21
通讯作者: 崔香丽 E-mail:cuixlcxl@sina.com,yue_tian@sina.com
基金资助:
国家自然科学基金（81272695）；山西省自然科学基金（20160D011107）

Protective effect of simvastatin on kidney of rats with diabetes mellitus and the possible mechanism

WAN Xin¹, WANG Xi¹, LI Fan-lu¹, WU Ya-li¹, LIU Xin¹, CHEN Huan-zhen², YANG Jing³, CUI Xiang-li¹

1. Department of Physiology, College of Preclinical Medicine, Shanxi Medical University, First Hospital of Shanxi Medical University, Taiyuan 030001, China;
2. Department of Cardiovascular Internal Medicine, First Hospital of Shanxi Medical University, First Hospital of Shanxi Medical University, Taiyuan 030001, China;
3. Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030001, China

Received:2017-09-25 Revised:2018-02-28 Online:2018-07-28 Published:2019-02-21
Supported by:
国家自然科学基金（81272695）；山西省自然科学基金（20160D011107）

摘要/Abstract

摘要： 目的：观察辛伐他汀对糖尿病大鼠肾脏损伤的保护作用并探讨其可能的分子机制。方法：24只SD大鼠随机分为正常对照（NC，n=8）组和糖尿病造模组（n=16）。糖尿病造模组大鼠采用55 mg/kg链脲佐菌素（STZ）单次腹腔注射的方法建立糖尿病大鼠模型。造模成功后，糖尿病模型大鼠随机分为糖尿病（DM）组和糖尿病+辛伐他汀（DM+Sim）组。DM+Sim组大鼠每天给予辛伐他汀40 mg/kg灌胃，1次/日，连续4周。采用组织病理学方法观察肾脏的形态学改变和间质纤维化；采用分子生物学方法检测肾脏组织中内质网应激、炎性因子的表达以及细胞凋亡。结果：①与NC组相比，DM组可见肾小球和肾小管间质有明显的病理学改变，胶原纤维明显红染，呈不均匀分布；DM+Sim组形态学以及纤维化有明显改善。②DM组大鼠肾组织GRP78、p-IRE1α、NF-κB p65、MCP-1表达均高于NC组（P<0.05），DM+Sim组GRP78、p-IRE1α、NF-κB p65、MCP-1表达较DM组均下降（P<0.05）。③TUNEL法检测，NC组肾小球及肾小管存在少量凋亡的细胞，DM组肾小球及肾小管存在大量凋亡的细胞（P<0.01）；与DM组比较，DM+Sim组凋亡的细胞明显减少（P<0.01）。结论：给予糖尿病大鼠辛伐他汀后，肾脏形态学以及纤维化明显改善，细胞凋亡明显减少。其对糖尿病肾脏的保护作用与抑制内质网应激和NF-κB炎症信号通路及减少肾脏细胞的凋亡有关。

关键词: 大鼠, 糖尿病, 肾脏, 辛伐他汀, 内质网应激, 炎症

Abstract: Objective: To observe the protective effect of simvastatin on renal injury in diabetic rats and to explore the possible molecular mechanism. Methods: Twenty-four SD rats were randomly divided into normal control (NC) group (n=8) and modeling group (n=16).The rats in modeling group were injected with streptozotocin intraperitoneally at a dose of 55 mg/kg to establishing diabetic rat model. After diabetic ratmodel established successfully, the diabetic rats were randomly subdivided into diabetes mellitus (DM) group and diabetes mellitus + simvastatin (DM+Sim) group (n=8).Rats in DM+Sim group were given simvastatin at a dose of 40 mg/kg by oral gavages, once a day for 4 weeks. Morphological changes and interstitial fibrosis of kidney were observed by histopathological method. The expressions of relative protein in endoplasmic reticulum stress, inflammatory molecules in renal tissues and cells apoptosis were detected by molecular biology method. Results: ① Compared with NC group, the pathological changes of glomerulus and tubulointerstitium were obvious, and the collagen fibers were obviously erythrophilous and unevenly distributed in DM group. Compared with DM group, the morphological changes and fibrosis were significantly improved in DM+Sim group. ② The expressions of GRP78, p-IRE1α, NF-κB p65 and MCP-1 in DM group were significantly higher than those in NC group (P<0.05), while the expressions of GRP78, p-IRE1α, NF-κB p65 and MCP-1in DM + Sim group were decreased (P<0.05). ③ There were a small number of apoptotic nuclei in the glomeruli and adjunctive renal tubules in NC group detected by TUNEL assay, while there were a large number of apoptotic nuclei in DM group (P<0.01). The number of apoptotic nuclei was decreased significantly in DM+Sim group (P<0.01). Conclusion: Morphologicalchanges and fibrosis of renal tissue are improved obviously, and the number of apoptotic cells is decreased significantly after administration of simvastatin in diabetic rats. Simvastatin exertsthe protective effect on diabetic nephropathy by inhibiting endoplasmic reticulum stress and NF-κB inflammatory signaling pathway, and reducing renal cell apoptosis.

Key words: rats, diabetes mellitus, kidney, simvastatin, endoplasmic reticulum stress, inflammation

宛欣, 王茜, 李凡璐, 吴亚俐, 刘鑫, 陈还珍, 杨静, 崔香丽. 辛伐他汀对糖尿病大鼠肾脏的保护作用及其可能机制[J]. 中国应用生理学杂志, 2018, 34(4): 313-317.

WAN Xin, WANG Xi, LI Fan-lu, WU Ya-li, LIU Xin, CHEN Huan-zhen, YANG Jing, CUI Xiang-li. Protective effect of simvastatin on kidney of rats with diabetes mellitus and the possible mechanism[J]. CJAP, 2018, 34(4): 313-317.

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辛伐他汀对糖尿病大鼠肾脏的保护作用及其可能机制

Protective effect of simvastatin on kidney of rats with diabetes mellitus and the possible mechanism

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