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目的探讨乙醛脱氢酶2(ALDH2)在急性高血糖加重大鼠心肌缺血/再灌注(I/R)损伤中的活性变化及作用。方法 48只雄性Wistar大鼠随机分为假手术组(SHAM组)、盐水对照组(CON组)、高糖组(HG组)和高糖+Alda-1干预组(HG+Alda-1组),每组12只。采用左冠脉前降支(LAD)结扎缺血30 min,再灌注1 h,建立大鼠心肌I/R模型。在建立大鼠心肌I/R模型同时,经颈静脉给予首负荷剂量50%葡萄糖(3 g/kg),使大鼠血糖浓度迅速升高至20~28 mmol/L,持续微量泵入[4 m L/(kg·h)],使大鼠血糖浓度维持在20~28 mmol/L,至再灌注结束。SHAM组和CON组给予0.9%Na Cl(6 m L/kg)。HG+Alda-1组给予Alda-1(8.5 mg/kg)微量泵入,至再灌注结束。再灌注结束后取心脏,采用比色法检测ALDH2活性的变化,HE染色观察心肌组织形态学变化,TTC染色法检测心肌梗死面积,TUNEL法检测心肌细胞凋亡情况。结果与CON组相比,HG组在缺血期和再灌注期血糖浓度明显升高[(23.4±0.21)vs(5.8±0.21)mmol/L,P<0.01]。HG组ALDH2活性明显低于CON组[(69.1±5.16)%vs(87.0±4.30)%,P<0.05]。HG组心肌梗死面积明显高于CON组[(38.2±3.30)%vs(26.8±2.53)%,P<0.05];HG+Alda-1组心肌梗死面积明显低于HG组[(27.8±2.50)%vs(38.2±3.30)%,P<0.05]。HG组心肌细胞凋亡指数明显高于CON组[(16.1±0.83)%vs(13.1±0.39)%,P<0.05];HG+Alda-1组心肌细胞凋亡指数明显低于HG组[(13.6±0.51)%vs(16.1±0.83)%,P<0.05]。结论急性高血糖可加重I/R大鼠的心肌梗死面积及心肌细胞凋亡,使心肌ALDH2的活性降低;增强ALDH2活性可显著减少急性高血糖大鼠I/R后的心肌梗死面积及心肌细胞凋亡。
Objective To investigate the changes and the role of ALDH2 in myocardial ischemia / reperfusion (I / R) injury induced by acute hyperglycemia in rats. Methods Forty eight male Wistar rats were randomly divided into sham operation group (SHAM group), saline control group (CON group), high glucose group (HG group) and high glucose + Alda-1 intervention group (HG + Alda-1 group) , 12 in each group. Left anterior descending coronary artery (LAD) was used to ligate ischemia for 30 min and then reperfusion for 1 h to establish rat myocardial I / R model. At the same time, the first loading dose of 50% glucose (3 g / kg) was administered via the jugular vein while rat I / R model was established. The blood glucose level of rats was rapidly increased to 20-28 mmol / L, m L / (kg · h)], the rat blood glucose concentration was maintained at 20 ~ 28 mmol / L, to the end of reperfusion. The SHAM group and CON group were given 0.9% NaCl (6 m L / kg). HG + Alda-1 group was given a small amount of Alda-1 (8.5 mg / kg) pumped until the end of reperfusion. The heart was taken after reperfusion, the change of ALDH2 activity was detected by colorimetry, the change of myocardial morphology was observed by HE staining, the area of myocardial infarction was detected by TTC staining and the apoptosis of cardiomyocytes was detected by TUNEL method. Results Compared with CON group, HG group had significantly higher blood glucose levels during ischemia and reperfusion [(23.4 ± 0.21) vs (5.8 ± 0.21) mmol / L, P <0.01]. ALDH2 activity in HG group was significantly lower than that in CON group [(69.1 ± 5.16)% vs (87.0 ± 4.30)%, P <0.05]. The area of myocardial infarction in HG + Alda-1 group was significantly higher than that in CON group [(38.2 ± 3.30)% vs (26.8 ± 2.53)%, P <0.05] % vs (38.2 ± 3.30)%, P <0.05]. The apoptosis index of cardiomyocytes in HG + Alda-1 group was significantly higher than that in CON group [(16.1 ± 0.83)% vs (13.1 ± 0.39)%, P <0.05] 13.6 ± 0.51)% vs (16.1 ± 0.83)%, P <0.05]. Conclusions Acute hyperglycemia can increase myocardial infarct size and myocardial apoptosis in I / R rats and decrease the activity of ALDH2 in myocardium. Increasing the activity of ALDH2 can significantly reduce the myocardial infarct size and myocardial cells in acute hyperglycemic rats after I / R Apoptosis.