褪黑素对胰岛素抵抗大鼠皮下脂肪组织瘦素表达的作用观察

Effect of melatonin on expression of leptin in subcutaneous fat tissue in insulin-resistant rats

目的探讨褪黑素(MLT)对胰岛素抵抗(IR)大鼠皮下脂肪组织瘦素(Lep)及其mRNA表达的影响。方法将37只SD大鼠随机分为模型组(n=27)和对照组(CN组,n=10)。CN组以普通饲料喂养。模型组以高糖膳食喂养6周复制IR大鼠模型,将建模成功的20只IR大鼠随机分为胰岛素抵抗组(IR组)和褪黑素组(MLT组),每组10只。MLT组从第7周开始,给予MLT 10mg/(kg·d)灌胃,持续6周。第12周末采用免疫组化和RT-PCR法检测各组大鼠腹股沟处皮下脂肪组织Lep及其mRNA的表达。结果与IR组相比,MLT组大鼠收缩压(SBP)、血清Lep、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)和胰岛素抵抗指数(HOMA-IR)均降低(P<0.01),血清超氧化物歧化酶(SOD)活性升高(P<0.01)。三组大鼠FPG和2hPPG均在正常范围。各组间体重比较差异无统计学意义(P>0.05)。IR组皮下脂肪组织Lep及其mRNA表达水平显著高于CN组和MLT组(P<0.01)。结论褪黑素可显著改善高糖膳食诱导的IR大鼠的IR和氧化应激状况,并能抑制皮下脂肪组织Lep及其mRNA的过度表达。

Objective To investigate the effect of melatonin （MLT） on protein and mRNA expression of leptin （Lep） in subcutaneous fat tissue in insulin resistance （IR） rats. Methods Thirty seven Sprague-Dawley （SD） rats were randomly divided into model group （n=27） and control group （CN group, n=10）. Rats in model group were fed with high glucose diet for 6 weeks. Twenty rats having developed IR in the model group were further randomly divided into two groups： IRgroup （n=10） and melatonin group （MLT group, n=10）. Rats in CN group and MLT group were fed with 10mg/（kg.d） of standard chow or MLT, respectively, for 6 weeks from the beginning of the 7th week. At the end of the 12th week, the subcutaneous fat tissue was harvested from bilateral inguinal areas of the rats for the evaluation of the protein and mRNA expression of Lep by immunohistochemistry and RT- PCR. Results Systolic blood pressure （SBP）, fasting serum leptin （Lep）, triglycerides （TG）, low density lipoprotein cholesterol （LDL-C）, malondialdehyde （MDA） and homeostasis model assessment insulin resistance （HOMA-IR） were significantly lower （P〈0.01）, while the serum superoxide dismutase （SOD） was significantly higher in MLT group compared with those in IR group （P〈0.01）. The levels of fasting plasma glucose （FPG） and 2-hour postprandial plasma glucose （2hPPG） remained in normal range, and the body weight showed no significant difference among the three groups （P〉0.05）. The protein and mRNA expressions of Lep in subcutaneous adipose tissue were significantly higher in IR group than in CN group （P〈0.01）, while they were significantly lower in MLT group than in IR group （P〈0.01）. Conclusion MLT may improve IR and the status of oxidation stress, and inhibit the over expression of Lep protein and mRNA in subcutaneous fat tissue in the high-glucose diet-induced IR rats.