硫化氢对糖尿病大鼠心肌损伤的保护作用及抗凋亡机制研究  

The protection against myocardial damage in diabetic rats by hydrogen sulfide and the research on their anti-apoptosis mechanisms

作　　者：梁瑞娟 LIANG Rui-juan(Puyang Hospital of TCM,Puyang Henan 457001,China)

机构地区：[1]濮阳市中医院,河南濮阳457001

出　　处：《中国卫生工程学》2018年第4期504-506,共3页Chinese Journal of Public Health Engineering

摘　　要：目的探讨硫化氢(H2S)对糖尿病大鼠心肌损伤的保护作用和抗凋亡机制。方法选择雄性SD大鼠40只作为研究对象,随机分为正常对照组、糖尿病对照组(STZ组)、糖尿病硫化氢钠(NaHS)治疗组(NaHS+STZ组)和NaHS对照组,每组10只。通过腹腔注射链脲佐菌素(STZ)45 mg/kg来构建糖尿病大鼠模型,NaHS+STZ组及NaHS对照组腹腔注射硫化氢(H2S)供体NaHS。8 w后处死大鼠并离体进行心脏灌流,测定左心室动力学指标,在电镜下观察心肌细胞超微结构改变情况,通过分光光度法观测心肌组织半胱天冬蛋白酶3(Caspase-3)的活性,RT-PCR法测定左心室心尖组织B淋巴细胞瘤-2基因(Bcl-2)和Bax mRNA的表达。结果 STZ组的左心室发展压(LVDP)为(4.35±1.58)kPa、左心室内压最大上升速率和下降速率(±dp/dt max)为(77.27±28.88)kPa/s、(158.91±33.14)kPa/s,均较正常组明显降低;左心室舒张末压(LVEDP)明显升高,差异均有统计学意义(均P<0.05);NaHS+STZ组与STZ组比较,LVDP、±dp/dt max增加,LVEDP降低,差异均有统计学意义(均P<0.05)。电镜观察发现,正常组大鼠心肌细胞纤维排列规则,线粒体膜结构正常,体积无肿胀,嵴规则统一;STZ组心肌纤维断开,线粒体肿大,嵴断裂或消失;NaHS组与正常组无明显差异;NaHS+STZ组与STZ组相比,心肌纤维断裂较少,线粒体肿大较轻,嵴断裂极少。STZ组Caspase-3活性为(0.87±2.13),与正常组比较活性增加;NaHS+STZ组Caspase-3活性为(0.65±1.34),与STZ组比较活性降低,差异均有统计学意义(P<0.05)。STZ组与正常组Bcl-2/Bax比较mRNA比值降低,NaHS+STZ组与STZ组比较Bcl-2/Bax mRNA比值升高,差异均有统计学意义(P<0.05)。结论H2S能够保护糖尿病大鼠心肌,其机制可能是抗心肌细胞凋亡。Objective To investigate the protection against myocardial damage in diabetic rats by hydrogen sulfide（H_2S）and the research on their anti-apoptosis mechanisms.Methods The subjects of this study were selected from 40 male SD rats which were evenly divided into the normal control group,diabetic control group（STZ group）,sodium hydrosulfide treating diabetic group（NaHS＋STZ group）,and NaHS group on a random basis,each with 10 rats.A diabetic rat model was built through streptozotocin（STZ） by intraperitoneal injection with a dosage of 45 mg/kg.The NaHS ＋STZ group was treated with H2S donor NaHS 8 weeks later,isolated heart perfusion was adopted to determine the left ventricular dynamic indexes,electron microscope to observe the changes in ultrastructure of heart cells,spectrophotometry to observe the activity of（Cysteine aspartatespecific proteinase 3（Caspase-3） and RT-PCR to detect B-cell lymphoma-2（Bcl-2） and Bax mRNA expressions.Results In regard of left ventricular dynamic indexes,the maximum rising and descending rates（±dp/dtmax） of left ventricular diastolic pressure（LVDP） and left ventricular pressure of STZ group significantly dropped as compared with the normal control group,while the left ventricular end-diastolic pressure went in the contrary,with a big statistical difference（P〈0.05）.No big difference was seen between the NaHS group and the normal group.Compared with STZ group,NaHS＋STZ had higher LVDP and±dp/dt maxbut lower LVEDP with a big difference（P〈0.05）.In terms of changes in ultrastructure,STZ had broken cardiac muscle fibers,swelled mitochondrias,and crests that were ruptured or disappeared.NaHS had no obvious difference from the normal group.Compared with STZ group（0.87±2.13）,the broken cardiac muscle fibers of NaHS＋STZ group partially recovered,its mitochondrias swelling got normal reduce,its crests were partially broken and the structure was markedly improved（P〈0.05）.In the respect of Caspase-3（0.65±1.34） activity,NaHS＋STZ

关 键 词：硫化氢 糖尿病大鼠 心肌损伤 抗凋亡机制 

分 类 号：R587.1[医药卫生—内分泌]