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.
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.