脂联素在糖尿病心肌病心肌间质纤维化中的作用机制研究

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目的探讨脂联素(adiponectin,APN)在糖尿病心肌病大鼠心肌间质纤维化中的抑制作用及其实现机制。方法取72只6周龄的清洁级雄性Wistar大鼠,随机分为对照组、实验组、模型组,每组24只,实验前所有大鼠正常喂养1周后测体重和血糖、尿糖。模型组、实验组分别给予空腹一次性注射链脲佐菌素(1%STZ,55 mg/kg)制备糖尿病模型,对照组腹腔注射同体积枸橼酸-枸橼酸钠缓冲液,72 h后模型组、实验组大鼠尾静脉采血测血糖>16.7 mol/L;尿糖(+++~++++),且具有体重减轻,多饮、多食、多尿现象为糖尿病成膜。造模后实验组(APN组)、模型组(Saline组)每天分别给予腹腔注射APN、Saline,持续至造模后第16周末。分别于8、12、16周末空腹麻醉取材评定糖尿病发病程度,测定心脏超声评估心功能;取心脏病理切片进行Masson染色拍片,扫描,采用图像分析仪定量心肌组织胶原的含量以评定心肌纤维化情况;心脏病理切片进行DHE染色以评估氧化应激情况。结果 Saline组至16周末死亡5只,发生糖尿病大鼠为17只(89.5%);而APN组无死亡,7只发生糖尿病(29.2%)。与Saline组大鼠相比,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)。结论早期的APN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 inhibitory effect and mechanism of adiponectin (APN) on myocardial interstitial fibrosis in diabetic cardiomyopathy rats. Methods Totally 72 male Wistar rats of 6 weeks of age were randomly divided into control group, experimental group and model group, with 24 rats in each group. Before the experiment, all rats were fed with normal body weight and blood glucose and urine glucose immediately after one week. The model group and the experimental group were given a fasting fasting streptozotocin (1% STZ, 55 mg / kg) to prepare the model of diabetes mellitus, the control group were intraperitoneally injected with the same volume of citrate - citrate buffer, 72 h In the model group and the experimental group, the tail vein blood was collected to measure blood glucose> 16.7 mol / L; urine glucose (+++ ~ ++++), and weight loss, polydipsia, polyphagia and polyuria were detected. The model group (APN group) and the model group (Saline group) were given intraperitoneal injection of APN and Saline daily until the end of the 16th week after modeling. Fasting anesthesia was taken at the end of 8, 12 and 16 weeks to assess the incidence of diabetes mellitus, and cardiac function was assessed by echocardiography. Masson stained sections of cardiac pathology were taken and scanned. The myocardial collagen content was quantified by image analyzer to assess myocardial fibrosis Heart sections were subjected to DHE staining to assess oxidative stress. Results In the Saline group, 5 were dead at the end of the 16th week and 17 (89.5%) were developed in the diabetic group. No deaths were found in the APN group and 7 of 21 (29.2%) were diabetic. The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were significantly decreased in APN group compared with Saline group (P <0.05), the short axis shortening (FS) and ejection fraction (EF) increased significantly (P <0.05), and the volume fraction of left ventricular collagen decreased significantly (P <0.05) The relative luminescence value of DHE staining was significantly weakened (P <0.05). Conclusion Early APN intervention can reduce myocardial fibrosis in diabetic cardiomyopathy rats through anti-oxidative stress.
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