慢性低度炎症肥胖小鼠造模与模拟节食的抗炎减肥机理研究-中医临床基础专业毕业论文.docxVIP

研究生优秀毕业论文 分析评价了高脂+高剂量(1．2mg／kg)脂多糖与低剂量(0．25mg／kg)脂多糖诱导 分析评价了高脂+高剂量(1．2mg／kg)脂多糖与低剂量(0．25mg／kg)脂多糖诱导 肥胖小鼠血清中40种促炎症细胞因子及肝脏中84种脂肪肝相关基因表达水平。结果 表明，高脂+高剂量脂多糖仅轻微卜调促炎症细胞因子及部分活化脂肪肝相关基冈， 而一氧化氮及3一硝基酪氨酸水平先升后降，推测高剂量脂多糖可能诱生抗脂多糖抗体 并清除脂多糖，从而减轻脂多糖诱导脂肪在肝脏的蓄积。相反，高脂十低剂量脂多糖 可大幅上调促炎症细胞因子并大量活化脂肪肝相关基因，但经给药治疗后表达水平全 部恢复正常。 高脂诱导肥胖小鼠模型的体脂比和肝指数均比对照高，差异达到极显著水平 (尺0．001)，血清胆固醇含量的差异也达到显著水平(尺O．05)。用芦荟虫草丹灌 胃后，处理组的体脂比和肝指数均比模型组低，其中造模前给药的下降程度达到极显 著水平(P(O．01)，造模后给药的下降程度达到显著水平(／2(0．05)，表明该药不仅 能预防肥胖，而且能治疗肥胖。通过肠道菌群分类培养发现，芦荟虫草丹能加速体内 大肠杆菌生长并促进带菌排便，也能促进体外培养的大肠杆菌增殖，表明该药可能通 过排菌清肠达到减肥曰的。 结论 本研究首次发现低剂量脂多糖可诱发全身慢性低度炎症，并证实抗疟药青蒿琥酯 和缓解心绞痛药硝酸甘油能模拟2，4一二硝基苯酚发挥其潜在减肥作用，还阐明了3种 单体药消炎、抗缺氧、抗DNA损伤和抗血管新生的减肥机理，同时也验证了1种复方药 的排菌清肠减肥机理。由于非热量限制(不节食)减肥方式更易被人接受，因此这类 减肥药将更受欢迎，也更有开发前景。 关键词：肥胖；炎症；2，4二硝基苯酚；青蒿琥酯；硝酸甘油 II Chron Chron i c I ow-grade I nf I ammatory obese mouso mode l—based stud i OS on dietin91Ilimic anti—infIammatory weight reduotion SpeciaIty：CI inicaI Basi Of TraditionaI Chinese MediCine Author：Gao 0ian Tutor：Zeng 0ingping Abstract ObJect ive In accompany with the improved nutritional standards and altered l ife styles of humans，overweight and obese popul ations throughout the world gradually overwhelming，and obesity—originated health and societal issues become and severe．Ilow to reduce body weight and prevent the obesity——related diseases remaiDS the most concerned topiCS and hot——spots under investigations．The present study intends to val idate suggested “chronic low—grade inflammation iS originated from trace bacterial endotoxin” hypothesiS by comparing Lhe noninflammatory and inflammatory obese models induced by high—fat(HF)十high—dose 1 ipopolysaccharide(LPS)and HF +l ow-dose I,PS．Furthermore，the therapeut i effects of and compound medicines with weight—reducing potentialS will be evaluated．and their mechanisms of action will be also elucidated in order to a possibility of dieting—mimic calorie non—restriction anti—inflammatory weight reductj which should be beneficial to the future development of effective w