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。
Objective To investigate the effect of exogenous hydrogen sulfide from sodium hydrosulfide（Na HS） on cardiac thioredoxin（ Trx） system in diabetic rats. Methods Male Sprague-Dawley rats were randomly divided into a normal group,a diabetic group,and three Na HS（14,28 and 56 μmol/kg） treatment groups,with 6 rats in each group. Type 1 diabetes was induced in the groups by a single intraperitoneal（ i. p.） injection of streptozotocin. At the fifth week after modeling,the Na HS treatment groups were injected（ i. p.） with Na HS at the doses of 14,28 and 56 μmol/kg once a day,respectively.After the treatment for 4 weeks,the fasting blood glucose（ FBG） level and ventricular hemodynamic parameters were measured. The changes of myocardial pathomorphology were observed by HE staining. The ultrastructural changes of cardiomyocytes were observed by transmission electron microscopy. The levels of serum lactate dehydrogenase（ LDH）, creatine kinase（ CK）,and creatine kinase MB isozyme（ CK-MB） were examined using the kits. Serum interleukin（ IL）-1β,IL-6,and tumor necrosis factor α（ TNF-α） were assayed by ELISA. The levels of total antioxidant capacity（T-AOC）,lipid peroxide（LPO）,and malondialdehyde（ MDA） in myocardium were analyzed using the kits. The mRNA expression of heme oxygenase 1（ HO-1） was detected using reverse transcription PCR（ RT-PCR）. The expression levels of Trx,Trx-interacting protein（ TXNIP）,and nicotinamide adenine dinucleotide phosphate oxidase 2（ NOX2） in myocardium were measured using Western blotting. Results Compared with the normal group, the left ventricular systolic and diastolic functions were weakened in the diabetic group,and the myocardial morphological structure and ultrastructure were damaged obviously. The FBG,LDH,CK,CK-MB,IL-1β,IL-6,TNF-α,LPO and MDA levels increased,while the T-AOC level decreased. The myocardial Trx protein expression was reduced,while the expressions of HO-1 mRNA,TXNIP and NOX2 proteins were elevated in
作者
贾强
杨锐
刘小粉
王其一
卢浩宇
马善峰
JIA Qiang;YANG Rui;LIU Xiaofen;WANG Qiyi;LU Haoyu;MA Shanfeng(Department of Physiology;Department of Clinical Medicine, Bengbu Medical College, Bengbu 233030, China)
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2017年第10期1385-1391,共7页
Chinese Journal of Cellular and Molecular Immunology
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)
