不同剂量瘦素对2型糖尿病大鼠心肌缺血再灌注损伤的影响研究

Effect of Leptin Pretreatment on Myocardial Ischemic Reperfusion Injury in Type 2 Diabetic Rats

目的探讨不同剂量瘦素对2型糖尿病大鼠心肌缺血再灌注损伤(MIRI)的影响。方法 60只SPF级健康SD大鼠按照随机数字表法分为6组:正常对照组、糖尿病假手术组、糖尿病心肌梗死模型组(心肌梗死组)、糖尿病心肌梗死低剂量瘦素预处理组(低剂量组)、糖尿病心肌梗死中剂量瘦素预处理组(中剂量组)、糖尿病心肌梗死高剂量瘦素预处理组(高剂量组),每组10只。正常对照组普通饲料喂养,4周后空腹取血清及心脏标本。糖尿病5组均采用高糖高脂喂养4周后加链脲佐菌素(STZ)腹腔注射(35 mg/kg)复制2型糖尿病模型。糖尿病各组大鼠均于心肌梗死术后3 h取血清及心脏标本,测定大鼠空腹血糖(FBG)、空腹胰岛素(FINS)、瘦素、胰岛素抵抗指数(HOMA-IR)、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)及血脂水平。结果与正常对照组相比,糖尿病假手术组、心肌梗死组、低剂量组、中剂量组、高剂量组大鼠FBG、FINS、瘦素、HOMA-IR、TNF-α、MDA及三酰甘油(TG)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平均升高,高密度脂蛋白胆固醇(HDL-C)水平降低(P<0.05);与糖尿病假手术组相比,心肌梗死组、低剂量组、中剂量组、高剂量组大鼠FBG及瘦素水平均升高,心肌梗死组、高剂量组FINS及HOMA-IR升高,低剂量组、中剂量组FINS及HOMA-IR降低,心肌梗死组TNF-α、MDA水平升高,低剂量组、中剂量组、高剂量组TNF-α、MDA及HDL-C水平均升高而TG、TC、LDL-C水平降低(P<0.05);与心肌梗死组相比,低剂量组、中剂量组FBG、FINS、瘦素水平、HOMA-IR、TNF-α、MDA、TG、TC、LDL-C水平均降低,HDL-C水平升高(P<0.05)。结论 2型糖尿病大鼠在MIRI中存在高瘦素血症与胰岛素抵抗,给予一定浓度外源性瘦素预处理能够降低瘦素、HOMA-IR、TNF-α、MDA水平,以减轻由炎症、氧化应激、血脂紊乱及胰岛素抵抗所介导的损伤,从而降低糖尿病大鼠MIRI过程中的心肌损害作用。

Objective To study the effect of different doses of leptin pretreatment on myocardial ischemic reperfusion injury （MIRI） in type 2 diabetic rats. Methods 60 healthy male SD rats （SPF） were randomly divided into six groups with 10 in each group ： normal control group （ NC group）, DM - sham - operation group, DM - MIRI group, low - dose - leptin group, middle -dose -leptin group, and high -dose -leptin. NC group were fed on basic diet （4 weeks） , and the blood and heart sampies were obtained from each rat after 4 weeks. Type 2 diabetic rat models were reconstructed by adopting the method of feeding them on high fat/high sucrose diet （4 weeks） combined with streptozotocin （35 mg/kg） intraperitoneal injection. The blood and heart samples were obtained from the DM groups 3 h after reperfusion. The levels of.leptin, TNF-α, FBG, FINS, MDA, lip- ids and HOMA - IR were detected. Results Compared with normal rats, the FBG, FINS, leptin, HOMA - IR, TNF - α, MDA, TG, TC, LDL - C levels of DM - sham - operation group, low - close - leptin group, middle - dose - leptin group and high - dose - leptin groups were significantly increased （ P 〈 0. 05 ） , but HDL - C level was decreased （ P 〈 0.05 ） ; Compared with DM - sham - operation group, the FBG, leptin levels of the other four diabetic groups were increased （ P 〈 0. 05 ） , the FINS, HOMA - IR of DM - MIRI group and high - dose - leptin group was increased （ P 〈 0. 05 ） , the FINS, HOMA - IR of