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泽泻汤对代谢综合征大鼠治疗作用及机理的探讨
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摘要
目的:探讨泽泻汤对代谢综合征(MS)大鼠的治疗作用及其分子机理。方法:以高糖高脂饲料建立MS大鼠(雌雄)模型,将模型大鼠分为3组,分别给予泽泻汤(中药组)、西布曲明(西药组)和生理盐水(盐水组)灌胃,并继续高糖高脂饮食,连续4周。观察大鼠体重相关指标、血糖、血脂、血清胰岛素、瘦素和血浆神经肽Y(NPY)含量。应用免疫组化法检测下丘脑Ghrelin、TNF-α,NPY及其Y1受体亚型(NPYY1R,Y1R)和胰岛NPY及Y1R,用image-pro plus6.0进行平均光密度分析。结果:中药组大鼠体重、血糖、血脂(TG、TC、LDL-c)、血清胰岛素和瘦素、血浆NPY含量均显著降低;下丘脑Ghrelin、NPY及Y1R和胰岛NPY及Y1R平均光密度值亦显著低于生理盐水对照组。结论:泽泻汤能抑制MS大鼠的体重增长,降低血糖,调节脂代谢,其作用可能通过抑制下丘脑Ghrelin合成,下调下丘脑和胰岛NPY及Y1R的表达,从而调节摄食中枢兴奋性,改善胰岛B细胞功能,纠正胰岛素抵抗和瘦素抵抗而实现的。
Objective To explore the therapeutic effects of Zexie Tang on Metabolic syndrome(MS) rats as well as to make a study on the molecular mechanism. Methods Rats models(males and females) of Metabolic Syndrome were established by high sugar & fat diet, then they were randomly divided into 3 groups, including ZeXieTang decoction(TCM group), sibutramine (western medicine group) and saline group. After 4 weeks of oral administration and high sugar & fat diet, the changes of body weight and associated indicators, the levels of fasting blood-glucose(FBG), lipids, fasting insulin, serum leptin and plasma NPY were examined respectively. Meanwhile, Ghrelin, TNF-α, NPY and Y1 receptor subtype (NPYY1R,Y1R) in hypothalamus, NPY and Y1R in pancreatic islets were tested by immunohistochemistry. The density mean was analyzed by image-pro plus6.0. Results The body weight, levels of FBG, lipids, insulin, leptin and plasma NPY were reduced significantly in TCM group. The density mean of Ghrelin, NPY and Y1R in hypothalamus and of NPY and Y1R in pancreatic islets were significantly lower in TCM group than those in saline group. Conclusion Zexie Tang can inhibit the growth of body weight of MS rats, reduce the level of FBG and regulate lipid metabolism probably by inhibiting the synthesis of NPY and the expression of Y1R in hypothalamus and pancreatic islets, by which restrained the synthesis of Ghrelin in hypothalamus, regulated the excitability of the feeding center, improved the functions of pancreatic islets B cells and reduced the insulin resistance and leptin resistance.
引文
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