联麦氧钒对糖尿病大鼠内质网应激介导心肌细胞凋亡的抑制作用及其机制

doi:10.13481/j.1671-587x.20150317

吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (03): 522-526.doi: 10.13481/j.1671-587x.20150317

联麦氧钒对糖尿病大鼠内质网应激介导心肌细胞凋亡的抑制作用及其机制

李颖¹, 丛晓强², 赵良臣³, 谢林⁴, 刘娅⁴

1. 吉林省人民医院急诊内科, 吉林长春 130021;
2. 吉林大学第一医院心内科, 吉林长春 130021;
3. 吉林省吉林市中心医院心内科, 吉林吉林 132011;
4. 吉林大学公共卫生学院营养与食品卫生学教研室, 吉林长春 130021

收稿日期:2014-09-16 发布日期:2015-08-01
通讯作者: 丛晓强,主治医师(Tel:0431-88782883;E-mail:congxiaoqiang@hotmail.com) E-mail:congxiaoqiang@hotmail.com
作者简介:李颖(1980-),女,吉林省长春市人,主治医师,医学硕士,主要从事冠心病及心功能不全的诊断与治疗方面的研究。
基金资助:
吉林省卫生厅科研基金资助课题(2012Z095)

Inhibitory effect of BMOV on endoplasmic reticulum stress-induced cardiomyocyte apoptosis of diabetic rats and its mechanism

LI Ying¹, CONG Xiaoqiang², ZHAO Liangchen³, XIE Lin⁴, LIU Ya⁴

1. Department of Emergency Internal Medicine, People's Hospital, Jilin Province, Changchun 130021, China;
2. Department of Cardiology, First Hospital, Jilin University, Changchun 130021, China;
3. Department of Cardiology, Jilin Central Hospital, Jilin 132011, China;
4. Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun 130021, China

Received:2014-09-16 Published:2015-08-01

摘要/Abstract

摘要：

目的:探讨联麦氧钒(BMOV)对糖尿病(DM)大鼠内质网应激(ERS)介导的心肌细胞凋亡的抑制作用及可能的机制,为临床研究糖尿病心肌病(DCM)提供理论依据。方法:健康雄性Wistar大鼠35只,随机选取10只作为对照组,给予柠檬酸缓冲液(55 mg·kg^-1),正常饮水,维持4周。其余25只大鼠腹腔注射链佐脲酶素(STZ)1周建立DM模型,空腹血糖≥13.3 mmol·L^-1大鼠定为DM模型;选择20只随机分为DM组和BMOV组,每组10只。DM组大鼠正常饮水,继续维持3周。BMOV组大鼠饮水中加入BMOV,共维持3周。取各组大鼠心肌组织行TUNEL染色观察细胞凋亡情况;Western blotting法检测各组大鼠心肌组织中葡萄糖调节蛋白78(GRP78)、CCCAAT/增强子结合蛋白同源蛋白(CHOP)、X盒结合蛋白1(XBP-1)水平;qPCR法检测各组大鼠心肌组织中XBP-1 mRNA表达水平。结果:TUNEL染色,对照组大鼠心肌组织中见极少的凋亡细胞,凋亡指数(AI)为0.80±0.63;DM组较对照组心肌细胞凋亡明显增加,AI升高(P<0.05);BMOV组较DM组心肌细胞凋亡明显减少,AI降低(P<0.05);Western blotting法检测,与对照组比较,DM组大鼠心肌组织中GRP78、CHOP和XBP-1表达水平明显升高(P<0.05);与DM组比较,BMOV组大鼠心肌组织中GRP78、CHOP和XBP-1表达水平明显降低(P<0.05);qPCR法检测,与对照组比较,DM组大鼠心肌组织中XBP-1 mRNA表达水平明显升高(P<0.05);与DM组比较,BMOV组大鼠心肌组织中XBP-1 mRNA表达水平明显降低(P<0.05)。结论:BMOV对DM大鼠心肌细胞具有保护作用,其机制可能与抑制心肌细胞ERS及其介导的细胞凋亡有关联。

关键词: 联麦氧钒, 糖尿病心肌病, 内质网应激, X-盒结合蛋白1

Abstract:

Objective To investigate the inhibitroy effect of bis(maltolato)oxovanadium(Ⅳ) (BMOV) on endoplasmic reticulum stress(ERS)-induced apoptosis of cardiomyocytes of the rats with diabetes mellitus (DM) and possible mechanisms, and to provide a theoretical basis for the clinical study on diabetic cardiomyopathy(DCM). Methods 35 male Wistar rats were selected, among them 10 rats were randomly selected and used as control group, and they were admistrated intraperitoneally with citric acid buffer (55 mg·kg^-1) and normal drinking water for 4 weeks.The remaining 25 rats were admistrated intraperitoneally with streptozotocin (STZ).1 week later, the rats with the level of fasting blood glucose greater than or equal to 13.3 mmol·L^-1 were used as DM models. Finally 20 DM rats were randomly divided into DM group and BMOV group (n=10).The rats in DM group were administered with normal drinking water for 3 weeks.The rats in BMOV group were administered with BMOV in drinking water for 3 weeks.The myocardium tissue was taken for TUNEL staining to observe the apoptosis;Western blotting method was used to detect the levels of glucose-regulated protein 78 (GRP78), CCCAAT/enhancer binding homologous protein (CHOP), X-box binding protein 1(XBP-1);qPCR was used to dectect the XBP-1 mRNA expression levels in myocardium tissue of the rats in various groups. Results The TUNEL staining Results showed that the apoptotic cells in cyocardium tissue of the rats in control group were few, in control group the apoptotic index(AI) was 0.80 + 0.63;compared with control group, the apoptosis of myocardial cells in DM group was significantly increased, and the AI was increased (P<0.05);compared with DM group, the apoptosis of myocardial cells in BMOV group was significantly decreased, and the AI was decreased (P<0.05).The Western blotting Results showed that the expression levels of GRP78, CHOP.and XBP-1 of the rats in DM group were significantly higher than those in control group(P<0.05);and the expression levels of GRP78, CHOP and XBP-1 of the rats in BMOV group were lower than those in DM group(P<0.05).The qPCR Results showed that the XBP-1 mRNA expression level of the rats in DM group was higher than that in control group(P<0.05), and the XBP-1 mRNA expression level of the rats in BMOV group was lower than that in DM group(P<0.05). Conclusion BMOV has protective effects on the myocardial cells of the DM rats, and its mechanism may be related to inhibition of ERS and apoptosis of myocardial cells induced by ERS.

Key words: bis(maltolato)oxovanadium(Ⅳ), diabetic cardiomyopathy, endoplasmic reticulum stress, X-box binding protein 1

中图分类号:

R587.2

李颖, 丛晓强, 赵良臣, 谢林, 刘娅. 联麦氧钒对糖尿病大鼠内质网应激介导心肌细胞凋亡的抑制作用及其机制[J]. 吉林大学学报(医学版), 2015, 41(03): 522-526.

LI Ying, CONG Xiaoqiang, ZHAO Liangchen, XIE Lin, LIU Ya. Inhibitory effect of BMOV on endoplasmic reticulum stress-induced cardiomyocyte apoptosis of diabetic rats and its mechanism[J]. Journal of Jilin University Medicine Edition, 2015, 41(03): 522-526.

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联麦氧钒对糖尿病大鼠内质网应激介导心肌细胞凋亡的抑制作用及其机制

Inhibitory effect of BMOV on endoplasmic reticulum stress-induced cardiomyocyte apoptosis of diabetic rats and its mechanism

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