脂联素通过抗氧化应激降低糖尿病心肌病心肌纤维化

Adiponectin reduced myocardial fibrosis in diabetic cardiomyopathy through anti-oxidative stress

目的观察应用脂联素(APN)是否能够抑制糖尿病心肌病大鼠心肌间质纤维化,该效应是否通过抗氧化机制而实现。方法雄性SD大鼠60只,给予一次性腹腔注射链脲佐菌素(STZ,55 mg/kg)制备糖尿病模型,随机分为APN组、DETC+APN组、Saline组,每组20只,于造模前24 h、造模后每天分别给予腹腔注射APN、DETC+APN、Saline(APN:1.5×10^(-3)μg/kg;DETC:750 mg/kg),持续至造模后第16周末。16周末评定糖尿病发病率,糖尿病标准为造模12周后血糖大于1 6.7 mol/L且具有多饮、多食、多尿现象;测定心脏超声评估心功能;取心脏病理切片进行Masson's染色,以测定心肌纤维化情况;心脏病理切片进行DHE染色,以评估氧化应激情况。结果 Saline组和DETC+APN组大鼠至1 6周末分别死亡4、2只,发生糖尿病大鼠分别为14只(87.5%)和10只(55.5%);而APN组无死亡,6只发生糖尿病(30.0%)。与Saline组大鼠相比,APN组和DETC+APN组大鼠左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室舒张末期容积(LVEDV)和左心室收缩末期容积(LVESV)均显著减少(P<0.05),短轴缩短率(FS)和射血分数(EF)显著升高(P<0.05),左室胶原容量分数(CVF)显著减少(P<0.05),反映氧化应激情况的DHE染色相对发光值显著减弱(P<0.05)。与APN组大鼠相比,DETC+APN组大鼠LVEDD、LVESD、LVEDV和LVESV均显著增加(P<0.05),FS和EF显著降低(P<0.05),CVF显著增加(P<0.05),氧化应激显著增强(P<0.05)。结论 APN早期干预治疗能够通过抗氧化应激效应降低糖尿病心肌病大鼠心肌纤维化。

Objective To investigate the effect of Adiponectin （APN） on myocardial interstitial fibrosis and to determine whether anti-oxidative stress mediate the effect of APN on reducing myocardial fibrosis in diabetic eardiomyopathy. Methods 60 male SD rats were given single intraperitoneal injection of streptozotocin （STZ,55 mg/kg） to prepare the diabetic modle. Rats were randomly divided into APN groups,DETC＋APN group,Saline group,n 20 for each group. Three group rats were given intraper- itonealinjection of APN,DETC@APN,Saline separately（APN：1. 5×10^-3 μg/kg;DETC：750 mg/kg） in 24 h pre-STZ,daily post STZ and continued until the 16th week post STZ. At the end of 16 week,the incidence of diabetes was assessed. After 12 weeks of the STZ injection,rats whose blood glucose was higher than 16.7 mol/I, and who had polydipsia, hyperphagia and polyuria were considered to be diabete rats;At the end of the experiment,left ventricular end-diastolic diameter（I.VEDD） ,left ventricular end sys tolic diameter（LVESD） ,left ventricular end-diastolic volume（LVEDV） and left ventricular end systolic volume （LVESV）, fraction- al shortening（FS） and ejection fraction（EF） were determined by ultrasound. Then the collagen level was determined by Masson＇s staining,and the oxidative stress was assessed by DHE staining. Results 4 of 20 rats in Saline group and 2 of 20 in DETC＋APN group but no rat in APN groups died during the 16 weeks＇ treatment intervention. 14 of 16（87.5%） Saline group rats and 10 of 18 （55.5%） DETC-k APN group rats developed diabete. However,only 6 rat in APN group developed diabete （30.0%）. By the end of the experiment, compared wit h the Saline group, LVEDD, LVESD, LVEDV and LVESV were significantly reduced （P〈0.05 ）, FS and EF was significantly higher（P〈0.05） ,left ventricular collagen volume fraction （CVF） significantly reduced（P〈0.05） ,oxidative stress was significantly reduced（P〈0.05） in APN group and DETC --APN group. Compared with the APN rats,LVEDD, LVESD, LVEDV and LVESV were significantly increased （ P〈0.05）., FS and EF significantly decreased（ P〈0.05）, CVF increased significantly（P〈0.05）, Relative luminescence values of DHE staining reflecting the oxidative stress level significantly increased（P 〈0.05） in DETC＋ APN group. Conclusion The early intervention therapy of APN prevents myocardial fibrosis in rats with diabetic cardiomyopathy through anti-oxidative stress mechanism.