硫氢化钠通过激活硫氧还蛋白系统减轻糖尿病大鼠心肌损伤

发布时间：2018-12-31 08:51

【摘要】：目的观察外源性硫化氢的供体硫氢化钠(Na HS)对糖尿病大鼠心肌硫氧还蛋白(Trx)系统的影响。方法雄性SD大鼠随机分为正常组、糖尿病组、(14、28、56)μmol/kg Na HS处理组,每组6只。采用一次性腹腔注射链脲佐菌素的方法制备1型糖尿病大鼠模型。造模成功4周后,Na HS处理组大鼠每天分别腹腔注射Na HS溶液(14、28、56)μmol/kg。处理4周后,测空腹血糖值(FBG)和左心室动力学指标;HE染色观察心肌病变情况、透射电镜观察心肌超微结构变化;利用试剂盒检测血清乳酸脱氢酶(LDH)、肌酸激酶(CK)和肌酸激酶MB同工酶(CK-MB),ELISA检测血清白细胞介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)水平;利用试剂盒检测心肌组织总抗氧化能力(T-AOC)、脂质过氧化物(LPO)和丙二醛(MDA)含量;反转录PCR检测心肌组织血红素加氧酶1(HO-1)mRNA水平,Western blot法检测心肌组织Trx、Trx相互作用蛋白(TXNIP)和烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2)的蛋白水平。结果与正常组比较,糖尿病组左心室收缩和舒张功能均降低,心肌组织形态和心肌细胞超微结构损伤明显;FBG、LDH、CK、CK-MB、IL-1β、IL-6、TNF-α、LPO和MDA均明显增高,T-AOC明显下降;心肌Trx蛋白表达明显降低,HO-1 mRNA、TXNIP和NOX2蛋白表达明显增加。与糖尿病组比较,各剂量Na HS处理组中左心室收缩和舒张功能、心肌组织形态和心肌细胞超微结构均得到改善;LDH、CK、CK-MB、IL-1β、IL-6、TNF-α、LPO和MDA均下降,T-AOC增高;心肌组织HO-1 mRNA和Trx蛋白表达增强,TXNIP和NOX2蛋白表达降低。结论 Na HS处理可以减轻糖尿病大鼠心肌损伤,其机制可能与激活Trx系统,增强抗氧化能力及抑制炎症因子释放相关。
[Abstract]:Aim to observe the effect of exogenous hydrogen sulfide donor sodium sulfoxylate (Na HS) on thioredoxin (Trx) system in diabetic rats. Methods male SD rats were randomly divided into normal group, diabetes group and (14 ~ 28) 渭 mol/kg Na HS treatment group with 6 rats in each group. Type 1 diabetic rats were induced by single intraperitoneal injection of streptozotocin. Four weeks after successful modeling, rats in, Na HS treated group were intraperitoneally injected with Na HS solution (14: 2856) 渭 mol/kg. each day. After 4 weeks of treatment, fasting blood glucose (FBG) and left ventricular dynamics were measured, changes of myocardial ultrastructure were observed by HE staining and transmission electron microscopy. Serum lactate dehydrogenase (LDH),) creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB), ELISA) were detected by Elisa kit. Serum levels of interleukin 1 尾 (IL-1 尾), IL-6 and tumor necrosis factor 伪 (TNF- 伪) were measured. The total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) contents in myocardium were measured by kit. The level of heme oxygenase-1 (HO-1) mRNA in myocardial tissue was detected by reverse transcription PCR. The protein levels of Trx,Trx interacting protein (TXNIP) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) were detected by, Western blot method. Results compared with the normal group, the left ventricular systolic and diastolic function in the diabetic group was decreased, and the myocardial tissue morphology and myocardial ultrastructure were obviously damaged. FBG,LDH,CK,CK-MB,IL-1 尾, IL-6,TNF- 伪, LPO and MDA were significantly increased, T-AOC was decreased, Trx protein expression was significantly decreased, HO-1 mRNA,TXNIP and NOX2 protein expression was significantly increased. Compared with diabetic group, left ventricular systolic and diastolic function, myocardial tissue morphology and myocardial ultrastructure were improved in each dose of Na HS treatment group. LDH,CK,CK-MB,IL-1 尾, IL-6,TNF- 伪, LPO and MDA decreased, T-AOC increased, and HO-1 mRNA and Trx protein expression increased, TXNIP and NOX2 protein expression decreased. Conclusion Na HS treatment can reduce myocardial injury in diabetic rats, and its mechanism may be related to activation of Trx system, enhancement of antioxidant capacity and inhibition of inflammatory factor release.
【作者单位】：蚌埠医学院生理学教研室;蚌埠医学院临床医学系;
【基金】：安徽省高校自然科学研究重点项目(KJ2017A216,KJ2017A210) 蚌埠医学院科研重点项目(BYKY1621ZD) 国家级大学生创新创业训练项目(201510367007,201510367009)
【分类号】：R587.2

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