[1]曹军涛,王秀岩,郭宜姣,等.异丙酚对2型糖尿病大鼠心肌缺血再灌注损伤的保护作用及机制[J].新乡医学院学报,2019,36(10):917-921.[doi:10.7683/xxyxyxb.2019.10.004]
　CAO Jun-tao,WANG Xiu-yan,GUO Yi-jiao,et al.Protective effect and mechanism of propofol on myocardial ischemia reperfusion injury in type 2 diabetic rats[J].Journal of Xinxiang Medical University,2019,36(10):917-921.[doi:10.7683/xxyxyxb.2019.10.004]
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异丙酚对2型糖尿病大鼠心肌缺血再灌注损伤的保护作用及机制
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年10
页码:
917-921
栏目:
基础研究
出版日期:
2019-10-05

文章信息/Info

Title:
Protective effect and mechanism of propofol on myocardial ischemia reperfusion injury in type 2 diabetic rats
作者:
曹军涛1; 王秀岩1; 郭宜姣1; 刘　超2
(1.洛阳东方医院麻醉科，河南　洛阳　471003；2.天津市胸科医院心血管病研究所，天津　300222)
Author(s):
CAO Jun-tao1; WANG Xiu-yan1; GUO Yi-jiao1; LIU Chao2
（1.Department of Anesthesiology，Luoyang Dongfang Hospital，Luoyang 471003，Henan Province,China; 2.Institute of Cardiovascular Diseases，Tianjin Chest Hospital，Tianjin 300222，China）
关键词:
异丙酚; 2型糖尿病; 心肌缺血再灌注损伤; 细胞凋亡
Keywords:
propofol;  type 2 diabetes mellitus;  myocardial ischemia reperfusion injury;  apoptosis
分类号:
R587.1
DOI:
10.7683/xxyxyxb.2019.10.004
文献标志码:
A
摘要:
目的　探讨异丙酚缓解2型糖尿病大鼠心肌缺血再灌注（IR）损伤的作用机制。方法　选取成年雄性Wistar大鼠，腹腔注射链脲佐菌素（30 mg·kg-1）制备2型糖尿病模型。采用随机数字表法将54只2型糖尿病大鼠分为假手术组、IR组和异丙酚组，每组18只。IR组和异丙酚组大鼠采用结扎左冠状动脉前降支30 min，再灌注2 h的方式制备IR损伤模型；假手术组大鼠仅进行穿线，不结扎冠状动脉左前降支。异丙酚组大鼠在缺血前10 min静脉泵注异丙酚(6 mg·kg-1·h-1)至再灌注2 h。IR损伤模型建立后断头处死大鼠，取心肌组织，观察大鼠心肌组织病理学变化并计算心肌梗死范围；采用速率法检测各组大鼠血清肌酸激酶（CK）和乳酸脱氢酶（LDH）活性，采用比色法检测各组大鼠血清丙二醛（MDA）和超氧化物歧化酶（SOD）含量；Western blot法检测各组大鼠心肌组织中Bcl-2、Bax和Caspase-3蛋白表达量。结果　假手术组大鼠心肌细胞未见明显坏死和出血，无中性粒细胞浸润；IR组大鼠心肌细胞可见灶状坏死及出血，有明显的收缩带，并存在大量中性粒细胞浸润；异丙酚组大鼠心肌组织可见少量出血及中性粒细胞浸润，有少量固缩细胞。 IR组和异丙酚组大鼠心肌梗死范围大于假手术组（P<0.05）；异丙酚组大鼠心肌梗死范围小于IR组（P<0.05）。IR前3组大鼠血清LDH、CK、MDA及SOD水平比较差异无统计学意义（P>0.05）。IR后IR组和异丙酚组大鼠血清LDH、CK及MDA水平高于IR前，SOD水平低于IR前（P<0.05）；假手术组大鼠IR前后血清LDH、CK、MDA及SOD水平比较差异无统计学意义（P>0.05）。IR后，IR组和异丙酚组大鼠血清LDH、CK及MDA水平高于假手术组，SOD水平低于假手术组（P<0.05）；异丙酚组大鼠血清LDH、CK及MDA水平低于IR组，SOD水平高于IR组（P<0.05）。IR组和异丙酚组大鼠心肌组织中Bcl-2、Bax和Caspase-3蛋白相对表达量高于假手术组（P<0.05）；异丙酚组大鼠心肌组织中Bax和Caspase-3蛋白相对表达量低于IR组，Bcl-2蛋白相对表达量高于IR组（P<0.05）。结论　异丙酚能够有效缓解2型糖尿病大鼠心肌IR损伤，其机制与上调Bcl-2表达、下调Bax和Caspase-3的表达及抑制细胞凋亡有关。
Abstract:
Objective　To study the mechanism of propofol alleviating myocardial ischemia reperfusion(IR) injury in type 2 diabetes mellitus rats.Methods　Adult male Wistar rats were injected intraperitoneally with streptozotocin(30 mg·kg-1) to make type 2 diabetes mellitus model.Fifty-four rats with type 2 diabetes mellitus were randomly divided into sham operation group，IR group and propofol group,with 18 rats in each group.The rats in the IR group and the propofol group were ligated left anterior descending coronary artery for 30 minutes and were given reperfusion for 2 hours to prepare IR model;the rats in the sham-operation group underwent only threading without ligating left anterior descending coronary artery.The rats in the propofol group were injected intravenously with propofol(6 mg·kg-1·h-1) from 10 minutes before ischemia to 2 h after reperfusion.The rats were sacrificed after establishing the IR injury model，and the myocardial tissues were taken to observe the pathological changes of myocardial tissues and calculate the myocardial infarct size. The activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum were detected by rate method and the levels of myocardial malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured by colorimetric method；the expressions of Bcl-2，Bax and Caspase-3 protein in myocardium tissue of rats in each group were detected by Western blot.Results　There was no obvious necrosis and hemorrhage of myocardial cells and no neutrophil infiltration in myocardium tissue of rats in the sham operation group.In the IR group，the myocardial cells of rats showed focal necrosis and hemorrhage，with obvious contractile bands and a large number of neutrophil infiltration; a small amount of hemorrhage and neutrophils infiltration and a small amount of solid shrinkage cells were observed in myocardial tissue of rats in the propofol group.The myocardial infarction sizes of rats in the IR group and the propofol group were larger than those in the sham operation group (P<0.05);the myocardial infarction size of rats in the propofol group was smaller than that in the IR group (P<0.05).There was no significant difference in the serum levels of LDH，CK，MDA and SOD among the three groups before IR (P>0.05).The serum levels of LDH，CK and MDA after IR were higher than those before IR，and the serum level of SOD after IR was lower than that before IR in the IR group and the propofol group (P<0.05); there was no significant difference in the serum levels of LDH，CK，MDA and SOD before and after IR in the sham operation group (P>0.05).After IR，the serum levels of LDH，CK and MDA of rats in the IR group and the propofol group were higher than those in the sham operation group，and the serum level of SOD was lower than that in the sham operation group (P<0.05); the serum levels of LDH，CK and MDA of rats in the propofol group were lower than those in the IR group，and the serum level of SOD was higher than that in the IR group (P<0.05).The relative expressions of Bcl-2，Bax and Caspase-3 protein in the myocardial tissues of rats in the IR group and propofol group were higher than those in the sham group (P<0.05).The relative expressions of Bax and Caspase-3 protein in the myocardial tissue of rats in the propofol group was lower than those in the IR group，and the relative expression of Bcl-2 protein was higher than that in the IR group (P<0.05).Conclusion　Isoflavone can effectively alleviate IR damage of myocardium in type 2 diabetic mellitus rats.Its mechanism may be related to the up-regulation of Bcl-2 expression， down-regulation of the Bax and Caspase-3 expression，and the inhibition of apoptosis.

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更新日期/Last Update: 2019-10-05