首页  期刊介绍 征稿简则 编委会 期刊征订 广告服务 留言板 联系我们 English

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (5): 422-426.doi: 10.12047/j.cjap.5653.2018.096

• 研究论文 • 上一篇    下一篇

辛伐他汀对大鼠糖尿病所致心肌细胞凋亡的影响及其机制

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

  1. 1. 山西医科大学生理系省部共建细胞生理学重点实验室, 太原 030001;
    2. 山西医科大学第一医院心血管内科, 太原 030001
  • 收稿日期:2017-11-28 修回日期:2018-09-25 出版日期:2018-09-28 发布日期:2019-02-21
  • 通讯作者: 崔香丽,Tel:0351-4135329;E-mail:cuixlcxl@sina.com E-mail:cuixlcxl@sina.com
  • 基金资助:
    国家自然科学基金(81272695);山西省‘1331工程’重点学科建设计划经费资助;山西省自然科学基金(20160D011107)

Simvastatin prevented myocardium of diabetes rats from apoptosis through inhibition of oxidative stress

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

  1. 1. Department of Physiology, Shanxi Medical University, Taiyuan 030001;
    2. Department of Cardiovascular Internal Medicine, First Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2017-11-28 Revised:2018-09-25 Online:2018-09-28 Published:2019-02-21
  • Supported by:
    国家自然科学基金(81272695);山西省‘1331工程’重点学科建设计划经费资助;山西省自然科学基金(20160D011107)

摘要: 目的:探讨辛伐他汀对糖尿病所致心肌损伤的保护作用及可能机制。方法:24只SD大鼠(180~220) g随机分为对照组(control组,n=8)和模型组(n=16),模型组给予链脲佐菌素(STZ)腹腔注射建立糖尿病模型,然后随机将模型组分为糖尿病组(DM组,n=8)和糖尿病+辛伐他汀组(DM+S组,n=8),DM+S组给予辛伐他汀40 mg/(kg·d)灌胃四周,其余两组给予的等量生理盐水。实验结束后,取心脏,分光光度测定法测定大鼠心肌组织脂质过氧化物丙二醛(MDA)含量、超氧化物歧化酶(SOD)的活性,HE染色观察大鼠心肌病理学改变,TUNEL法检测大鼠心肌细胞凋亡,免疫组织化学法测定大鼠p53的表达;Western blot检测心肌组织p53,p53-phospho-serine15,Bax,Bcl-2等蛋白的表达。结果:①与对照组比较,DM组大鼠心肌组织MDA含量显著升高(P<0.01),SOD活性明显下降(P<0.01),与DM组比较,DM+S组大鼠SOD活性显著增加(P<0.01),MDA含量显著下降(P<0.01)。②HE染色结果表明,与对照组比较,DM组大鼠心肌细胞排列紊乱,结构不清晰,有大量炎性细胞浸润;与DM组比较,DM+S组的心肌细胞结构明显改善。③ TUNEL细胞凋亡检测结果表明,与control组相比,DM组心肌凋亡细胞阳性率显著增加(P<0.01),给予辛伐他汀后细胞凋亡明显减少(P<0.01);④免疫组织学检测结果显示,与对照组比较,DM组p53表达量显著增加,且p53在细胞质和细胞核中均有表达(P<0.01);与DM组比较,DM+S组p53表达量明显下降,p53在细胞质和核中均有表达,但核内表达量减少(P<0.01)。⑤ Western blot检测结果表明,与对照组比较,DM组大鼠p53,p53-Phospho-Serine15,Bax表达量显著升高(P<0.01),Bcl-2表达量减少(P<0.01);与DM组比较,DM+S组p53(P<0.01),p53-Phospho-Serine15(P<0.01),Bax (P<0.05)表达量显著下降,Bcl-2(P< 0.05)表达量显著增加。结论:辛伐他汀通过改善心肌结构异常、抑制氧化应激和心肌细胞凋亡对糖尿病导致的心肌损伤起到保护作用,其机制与p53介导的细胞凋亡通路相关蛋白的调控有关。

关键词: SD大鼠, 糖尿病, 心脏, 辛伐他汀, 凋亡, 氧化应激

Abstract: Objective: To investigate the protective effects and the possible mechanisms of simvastatin on myocardial injury induced by diabetes.Methods: Twenty-four SD rats (180~220)g were randomly divided into control group (control, n=8) and modeled groups(n=16), the modeled groups were injected with streptozotocin intraperitoneally to induce diabetes. Then the modeled rats were randomly divided into diabetes mellitus group (DM group, n=8) and diabetes mellitus + simvastatin group (DM+S group, n=8). Rats in DM+S group were treated with simvastatin at the dose of 40 mg/(kg·d)by gavage for 4 weeks, and the other two groups were treated with the same amount of saline. At the end of experiments, the heart tissues were collected for further observation. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in heart tissues were measured by spectrophotometry; HE staining of rat heart slides was used to observe the pathological changes; TUNEL assay was used to determine the apoptosis index of myocardial cells in each groups; The distribution of p53 in the heart tissues was evaluated by immunohistochemistry; Western blot was used to detect the expressions of p53, p53-phospho-serine 15, Bax and Bcl-2 in the heart tissues. Results: ①Compared with control group, the content of malondialdehyde (MDA) was increased while the activity of superoxide dismutase (SOD) was decreased significantly in DM group (P<0.01). After simvastatin administration, the activity of SOD was increased and the content of MDA was decreased significantly (P<0.01). ② HE staining results showed that the myocardial cells in the DM group were disorganized, with unclear morphological structure and a large number of inflammatory cells infiltration. Compared with DM group, the myocardial morphology in DM+S group was improved significantly. ③TUNEL staining results showed that the apoptosis index of myocardial cells in DM group was increased significantly compared with that of control group, and the apoptosis index was decreased significantly after the treatment of simvastatin (P<0.01).④ Immunohistochemistry showed that compared with control group,the expression of p53 in DM group was increased significantly, and was expressed in both cytoplasm and nucleus, while the expression of p53 in DM+S group was decreased and the expression of p53 in nucleus was decreased significantly (P<0.01). ⑤ The results of Western blot showed that the expression levels of p53, p53-phospho-serine15 and Bax were higher than those in control group, and the expression of Bcl-2 was lower than that in control group (P<0.01). After simvastatin administration, the expression levels of p53,p53-phospho-serine 15 (P<0.01) and Bax were decreased significantly (P<0.05) and the expression of Bcl-2 was increased (P<0.05). Conclusion: Simvastatin exerted protective effects on myocardial injury caused by diabetes through improving the abnormal morphological changes of diabetic myocardium, alleviating oxidative stress and inhibiting apoptosis of myocardial cells. The mechanism is related to the regulation of apoptosis pathway mediated by p53.

Key words: SD rats, diabetes mellitus, heart, simvastatin, apoptosis, oxidative stress

版权所有 © 2015 《中国应用生理学杂志》编辑部
京ICP备16058274号-1
地址:天津市和平区大理道1号,邮编:300050  电话:022-84655184  E-mail:tjzgyish@163.com
本系统由北京玛格泰克科技发展有限公司设计开发 技术支持:support@magtech.com.cn