基于肠道菌群探讨辣木叶醇提物降糖作用机制

发布时间：2018-05-16 01:24

本文选题：辣木叶 + 醇提物　；参考：《北京中医药大学》2017年硕士论文

【摘要】：糖尿病(Diabetes Mellitus,DM)是与多种代谢紊乱相关的一组疾病,其最主要的特点为由胰岛素分泌或利用不足所导致的慢性持续性高血糖。DM发病机制包括遗传以及环境等多种因素。目前DM呈世界范围流行趋势,患病人数逐年增长,并具有较高的死亡率,同时也给各国医疗支出带来了沉重的负担,严重威胁了人类的健康和发展。近年来,在传统医学的指导下,越来越多的天然植物药物被发现具有良好的降糖作用。辣木叶(Moringa oleifera Leaves)是原产于印度的一种天然植物药物,在传统印度医学中具有良好的降糖、抗炎、抗菌、降压的作用,并受到了各国研究者的重视。目前许多实验及临床研究证明了辣木叶优秀的降糖作用,但其相关的作用机制尚不明确,对于是否能通过影响肠道菌群而发挥降糖作用的研究还未见报道。本课题以自发性糖尿病ZDF大鼠为模型,以研究辣木叶醇提物(Ethanol extracts of Moringa oleifera Leaves,EoM)对ZDF糖尿病大鼠的降糖作用以及对其肠道菌群的影响,从而探讨EoM的降糖作用机制。目的采用自发性糖尿病ZDF(fa/fa)大鼠,观察EoM对ZDF大鼠的降糖作用,同时用16SrDNA高通量测序技术,研究EoM对ZDF糖尿病大鼠肠道菌群的影响,探讨EoM的降糖作用机制。方法雄性ZL大鼠10只,作为正常组,雄性ZDF(fa/fa)成模糖尿病大鼠40只按血糖随机分为四组:模型组,二甲双胍(Met)组,EoM低剂量(EoMl)组,EoM高剂量(EoMh)组;每组各10只,灌胃8周。每周测取空腹血糖;每两周测取体重;第5周、第6周分别测OGTT、ITT;实验结束后取血清测GLU、TG、TC、HDL、LDL;第2周取模型组大鼠新鲜粪便标本,实验结束后留取各组大鼠新鲜粪便标本,行16S rDNA高通量测序比较各组菌群变化情况。结果给药8周后,与正常组相比,各组大鼠体重增长显著减少(p0.01),EoMh组体重增长显著低于模型组(p0.05);EoMl组、EoMh组和Met组均有显著降低血清GL U水平的作用(p0.05、p0.01和p0.01);EoMh还能显著降低血清LDL水平和TG水平(p0.05)。16S rDNA高通量测序结果显示:第8周时,模型组肠道菌群多样性显著降低(p0.01);EoMh能显著提高ZDF糖尿病大鼠肠道菌群多样性(p0.05);EoMl和EoMh能使ZDF糖尿病大鼠拟杆菌门、普雷沃氏菌科、普雷沃菌属丰度显著降低(p0.05),厚壁菌门、乳杆菌门、乳酸杆菌属丰度显著升高(p0.05);EoMh还能够显著增加ZDF肠道瘤胃菌科丰度以及毛螺菌科丰度(p0.01和p0.05)。结论EoM具有降低ZDF糖尿病大鼠血糖的作用,且EoMh能降低ZDF糖尿病大鼠血脂,EoM具有治疗糖尿病的作用;EoM能增加ZDF糖尿病大鼠肠道菌群多样性、改善肠道菌群物种结构分布,且EoMh作用更为显著;EoM可能是通过调节肠道菌群从而发挥其治疗糖尿病的作用。
[Abstract]:Diabetes Mellitusus (DM) is a group of diseases associated with many metabolic disorders. The main characteristic of DM is that the pathogenesis of chronic hyperglycemia caused by insulin secretion or underutilization includes genetic and environmental factors. At present, DM has a worldwide epidemic trend, the number of patients has increased year by year, and has a high mortality rate. At the same time, it has brought a heavy burden to the medical expenditure of various countries, which has seriously threatened the health and development of human beings. In recent years, under the guidance of traditional medicine, more and more natural plant drugs have been found to have good hypoglycemic effect. Moringa oleifera Leavesi is a kind of natural plant medicine originating in India. It has been paid attention to by researchers all over the world because of its good anti-sugar, anti-inflammatory, antimicrobial and hypotensive effects in traditional Indian medicine. At present, many experiments and clinical studies have proved the excellent hypoglycemic effect, but its related mechanism is not clear, whether it can affect intestinal microflora and the effect of hypoglycemic effect has not been reported. The purpose of this study was to study the hypoglycemic effect of Ethanol extracts of Moringa oleifera Leavesus EoM on the intestinal microflora of ZDF diabetic rats, and to explore the mechanism of EoM's hypoglycemic effect on the model of spontaneous diabetes mellitus (ZDF) rats. Objective to observe the hypoglycemic effect of EoM on ZDF rats and to study the effect of EoM on intestinal microflora of ZDF diabetic rats by using 16SrDNA high-throughput sequencing technique, and to explore the mechanism of EoM hypoglycemic effect. Methods Ten male ZL rats were randomly divided into four groups according to blood glucose: model group, metformin group, EoM low dose EoMl group, EoM high dose EoMh group, 10 rats in each group for 8 weeks. Fasting blood glucose was measured weekly; body weight was measured every two weeks; OGTT ITT was measured at week 5 and week 6 respectively; serum was collected to measure LDL of GLU TGG TCU HDL; fresh feces were collected from rats in the model group at week 2, and fresh fecal specimens were taken from the rats in each group after the end of the experiment. High throughput sequencing of 16s rDNA was performed to compare the changes of flora in each group. Results after 8 weeks of administration, compared with the normal group, The weight gain of EoMh group was significantly lower than that of model group P0.05EoMl group and EoMl group and Met group had a significant effect on reducing serum GLU level. P0.05P0.01 and p0.01 EoMh also significantly decreased serum LDL level and TG level. 16s rDNA high flux. The sequencing results showed that at week 8, In the model group, the intestinal microflora diversity decreased significantly (P 0.01) and EoMh significantly increased the intestinal microflora diversity of ZDF diabetic rats. P0.05 EoMl and EoMh could significantly decrease the abundance of Bacteroides, Prevoaceae, Prevoaceae in ZDF diabetic rats. The abundance of Lactobacillus and Lactobacillus also significantly increased the abundance of ZDF enteric ruminal fungi, such as p0.01 and p0.05. Conclusion EoM can decrease the blood glucose of ZDF diabetic rats, and EoMh can reduce the blood lipids of ZDF diabetic rats. EOM can increase the diversity of intestinal flora and improve the distribution of intestinal microflora in ZDF diabetic rats. EoMh may play a more important role in the treatment of diabetes by regulating intestinal flora.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5

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