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中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (12): 1342-1346.

• 基础研究 • 上一篇    下一篇

乙醛脱氢酶2在糖尿病大鼠致心肌损伤中的变化

史晓俊1, 康品方1, 高琴2, 叶红伟2, 李正红2, 汤阳1, 王洪巨1   

  1. 1蚌埠医学院第一附属医院心血管科,
    2生理学教研室,蚌埠 233004,安徽
  • 收稿日期:2013-12-05 修回日期:2014-07-21 发布日期:2020-07-20
  • 通讯作者: 高琴,通信作者,女,博士,副教授,研究方向:心血管生理学。Tel:0552-3175268 E-mail:bbmcgq@126.com王洪巨,通信作者,男,博士,教授,研究方向:心血管病学。Tel:0552-3086103 E-mail:docwhj1101@163.com
  • 作者简介:史晓俊,男,学士,硕士生导师,主任医师,研究方向,心血管病学。Tel:0552-3086103 E-mail:shixiaojunbbmc@163.com
  • 基金资助:
    国家自然科学基金资助项目(81000074);蚌埠医学院科技发展基金(Bykf13A16)

Changes of aldehyde dehydrogenase 2 on myocardial injury in diabetic rats

SHI Xiao-jun1, KANG Pin-fang1, GAO Qin2, YE Hong-wei2, LI Zheng-hong2, TANG Yang1, WANG Hong-ju1   

  1. 1Department of Cardiovascular Medicine, the First Affiliated Hospital of Bengbu Medical College,
    2Department of Physiology, Bengbu 233004, Anhui, China
  • Received:2013-12-05 Revised:2014-07-21 Published:2020-07-20

摘要: 目的: 观察线粒体乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)在糖尿病大鼠不同阶段导致心肌损伤中的变化,并分析其可能机制。方法: 采用链脲佐菌素(streptozotocin,STZ)55 mg/kg 腹腔注射复制糖尿病大鼠模型,造模成功后分别于4、8、12周时行离体心脏灌流,测定血流动力学指标;采用酶联免疫吸附实验(ELISA)检测血浆白细胞介素1(IL-1)、白细胞介素4(IL-4)水平及心肌组织4-羟壬烯醛(4-hydroxynonenal,4-HNE)含量;测定心肌组织ALDH2活性;RT-PCR测定心肌组织Bax、Bcl-2 mRNA的表达。结果: 与对照组相比,糖尿病组左室发展压(left ventricular developed pressure,LVDP)、心率(HR)和左室做功(rate pressure product,RPP)明显降低(P<0.05 或 P<0.01),血浆IL-1水平增加(P<0.01),IL-4水平降低(P<0.01),心肌组织ALDH2活性下降(P<0.01),4-HNE含量增加(P<0.01);Bcl-2/Bax mRNA比值降低(P<0.01);随着糖尿病病程的延长,LVDP、HR和RPP进一步降低(P<0.01), 血浆IL-4水平降低(P<0.05 或P<0.01),IL-1水平增加,心肌组织ALDH2活性进一步降低(P<0.01),心肌组织4-HNE明显增加 (P<0.01)、而Bcl-2/Bax mRNA比值降低(P<0.05 或P<0.01)。结论: 随着糖尿病病程的延长,炎性损伤逐渐加重,凋亡增加,其机制可能与心肌ALDH2活性逐渐降低有关。

关键词: 糖尿病, 乙醛脱氢酶2, 4-羟壬烯醛, 炎性损伤, 细胞凋亡

Abstract: AIM: To investigate the changes of aldehyde dehydrogenase 2 (ALDH2) on myocardial injury in different stages of diabetic rats and analyze the related mechanism. METHODS: Diabetic (DM) model in SD rat was induced by a single intraperitoneal injection of 55 mg/kg streptozoticin (STZ). DM rats were divided into fourth week (DM4W), eighth week (DM8W) and twelfth week (DM12W) groups. The ventricular hemodynamic parameters were recorded, plasma interleukin-1 (IL-1), interleukin-4 (IL-4) and cardiac 4-hydroxynon-2-enal (4-HNE) levels were determined by enzyme-linked immuno sorbent assay (ELISA), cardiac ALDH2 activity was measured. The expressions of Bax and Bcl-2 at mRNA level of left anterior myocardium were detected by RT-PCR. RESULTS: In contrast to control group, in DM4W, DM8W and DM12W groups, left ventricular development pressure (LVDP), heart rate (HR) and left ventricular work (RPP) were decreased(P<0.01), plasma IL-1 level was increased while IL-4 level was decreased(P<0.01). Cardiac 4-HNE level was increased, and ALDH2 activity was decreased(P<0.01). The expression of Bax mRNA level was increased(P<0.01), Bcl-2 mRNA level was decreased(P<0.01) and Bcl-2/Bax mRNA were decreased(P<0.01). And with the development of diabetic progression, LVDP, HR, RPP, IL-4, ALDH2 activity and Bcl-2/Bax mRNA were further reduced(P<0.05 or P<0.01). 4-HNE and IL-1 levels were increased(P<0.05 or P<0.01). CONCLUSION: With the development of diabetes, cardiac ALDH2 activity was further decreased, which may be related to the increase of inflammatory injury and the happening of apoptosis.

Key words: diabetes, aldehyde dehydrogenase 2, 4-hydroxynon-2-enal, inflammatory injury, apoptosis

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