摘要
目的观察硫化氢(H2S)对糖尿病大鼠心肌损伤的保护作用及其抗凋亡机制。方法雄性SD大鼠随机分为正常对照组(NC组)、糖尿病对照组(DM组)、硫氢化钠(NaHS)治疗组(NaHS+DM组)和NaHS对照组(NaHS组)。采用链脲佐菌素(STZ)55 mg/kg腹腔注射诱导糖尿病大鼠模型,造模成功8周后行离体心脏灌流,测定左心室动力学指标;电镜观察心肌细胞超微结构改变;采用分光光度法检测心肌组织Caspase-3的活性;RT-PCR检测左心室心尖组织Bcl-2、Bax mRNA的表达。结果与NC组相比,NaHS组各项指标差异均无统计学意义(P>0.05),而DM组左心室发展压(LVDP)、左心室内压最大上升速率和下降速率(±dp/dt max)均明显降低(P<0.01);左心室舒张末压(LVEDP)明显增大(P<0.01);心肌纤维断裂,线粒体肿胀,嵴断裂消失;心肌组织Caspase-3的活性明显增加(P<0.01);Bcl-2/Bax mRNA比值降低(P<0.01)。与DM组相比,NaHS+DM组LVDP、±dp/dt max增加(P<0.05,P<0.01),LVEDP明显降低(P<0.05),心肌超微结构损伤明显改善,Caspase-3活性明显降低(P<0.01),Bcl-2/Bax mRNA比值升高(P<0.01)。结论 H2S对糖尿病大鼠心肌损伤具有保护作用,其机制可能与抗心肌细胞凋亡途径有关。
Objective To investigate the anti-apoptotic effect of hydrogen sulfide （ H2 S） on its cardioprotection in diabetic rats. Methods Thirty-two male SD rats were divided into four groups randomly： normal control group （ NC） , diabetic group （ DM） , NaHS ＋ diabetic group （ NaHS＋DM） and NaHS group （ NaHS） . Diabetic rat was induced by injection of streptozotocin at 55 mg/kg intraperitoneally. After 8 weeks, hearts were excised and per-fused on Langendorff apparatus. Left ventricular hemodynamic parameters were measured. The ultrastructures of myocardium were observed using electron microscopy, and the activity of Caspase-3 was analyzed by spectrophoto-metric method. The expressions of Bcl-2 and Bax at mRNA level in the left anterior myocardium were detected u-sing RT-PCR. Results There had no significant differences of all indexes between NC and NaHS groups （ P ＆gt;0.05） . However, compared with NC group, in diabetic rats, left ventricular developed pressure （ LVDP） , maxi-mal rise/fall rate of left ventricular pressure （ ＆#177;dp/dtmax） were decreased （P＆lt;0.01）, left ventricular end dias-tolic pressure （LVEDP） was increased （P＆lt;0.01）. The activity of Caspase-3 was increased（P＆lt;0.01）, while the ratio of Bcl-2/Bax at mRNA level was decreased（P＆lt;0.01）. The degeneration of myocardiac myofibrillae and ede-ma of mitochondria were shown in diabetic rats. Compared with DM group, the hemodynamic parameters were re-served , and the injury of myocardiac myofibrillae and mitochondria was attentuated when the diabetic rats were trea-ted with NaHS at 14 μmol/（kg＆#183;d）. Caspase-3 activity was also decreased （P＆lt;0.01）, and the ratio of Bcl-2/Bax at mRNA level was increased （P＆lt;0.01）. Conclusion H2S can protect myocardium in diabetic rats, may be related to suppressing the happening of cell apoptosis.
出处
《安徽医科大学学报》
CAS
北大核心
2014年第2期172-176,共5页
Acta Universitatis Medicinalis Anhui
基金
安徽省教育厅自然科学研究项目(编号:KJ2007B111、KJ2013B146)
蚌埠医学院科研项目(编号:BY0907、BYKY1312)
关键词
硫化氢
心肌损伤
糖尿病
凋亡
hydrogen sulfide
myocardium injury
diabetes mellitus
apoptosis
