利拉鲁肽对糖尿病大鼠肠道菌群的影响

发布时间：2019-05-22 08:03

【摘要】：背景糖尿病是一种代谢性疾病,以高血糖症为主要表现。2004年,中国已经成为仅次于印度的世界上发病人数最多的国家,糖尿病患者约4,000万,超过美国和欧洲的总和。我国糖尿病人群的主体是2型糖尿病患者,占全部糖尿病患者人数90%以上。GLP-1受体激动剂是新型的抗糖尿病药物,GLP-1的分泌与肠道菌群呈一定程度的相关性。肠道菌群是当前研究的热点,已证实其与多种代谢异常相关,包括肥胖和糖尿病。很多研究表明糖尿病、肠道菌群、GLP-1、短链脂肪酸、膳食纤维之间密切相关,但其中的机制和因果关系尚未完全清楚。研究目的1.研究利拉鲁肽对糖尿病大鼠肠道菌群多样性的影响；2.研究利拉鲁肽对糖尿病大鼠粪便短链脂肪酸的作用；3.研究糖尿病大鼠血糖、体重、肠道菌群与GLP-1类似物(利拉鲁肽)之间的关系。研究方法1.造模：高脂喂养8周龄雄性SD大鼠,4周后腹腔注射四氧嘧啶,选取随机血糖大于16.7mmol/L的大鼠,随机分组建立糖尿病大鼠模型；2.给药：将大鼠分为空白组,模型组、低剂量组、高剂量组,分别给予生理盐水和利拉鲁肽,每周监测血糖和体重等指标；3.给药10周后行OGTT试验;4.第16周麻醉,留取标本并处死;5.气相色谱分析检测大鼠粪便短链脂肪酸；6. MiSeq 16s-rDNA检测大鼠粪便菌群。研究结果1.利拉鲁肽能在一定程度上影响肠道菌群的丰度,糖尿病大鼠使用利拉鲁肽进一步降低了菌群的丰度；2.利拉鲁肽增加了糖尿病大鼠粪便短链脂肪酸的含量；3.发现模型组粪便标本中发现一种含量较多的抗糖肽细菌,学名Ruminococcus gauvreauii,与空白组、低剂量组、高剂量组均存在显著差异。结论利拉鲁肽与糖尿病大鼠肠道菌群的丰度呈负相关性、与菌群代谢产物(短链脂肪酸)呈正相关。这样的结果可能是由利拉鲁肽对胃肠道功能的影响相关。一种抗糖肽菌Ruminococcus gauvreauii在ALX糖尿病大鼠模型肠道菌群中的比例增高,在使用利拉鲁肽的组比例有所减低,正常大鼠的空白组中未检出,或许与GLP-1的作用相关。
[Abstract]:Background Diabetes is a metabolic disease, mainly characterized by hyperglycemia. In 2004, China became the world's largest number of patients after India, with about 40 million diabetics, more than the United States and Europe combined. The main body of diabetes mellitus in China is type 2 diabetes mellitus, accounting for more than 90% of all diabetic patients. GLP-1 receptor agonist is a new type of antidiabetic drug, and the secretion of GLP-1 is related to intestinal flora to a certain extent. Intestinal flora is the focus of current research, which has been confirmed to be related to a variety of metabolic abnormalities, including obesity and diabetes. Many studies have shown that diabetes, intestinal flora, GLP-1, short chain fatty acids and dietary fiber are closely related, but the mechanism and causality are not fully understood. The purpose of the study is 1. To study the effect of Lilaruin on intestinal flora diversity in diabetic rats. To study the effect of Lilaruin on short chain fatty acids in feces of diabetic rats. To study the relationship between blood glucose, body weight, intestinal flora and GLP-1 analogues in diabetic rats. Research method 1. Model: 8-week-old male SD rats were fed with high fat, and alloxan was injected intraperitoneally 4 weeks later. Rats with random blood glucose greater than 16.7mmol/L were randomly divided into two groups to establish diabetic rat model. Administration: the rats were divided into blank group, model group, low dose group and high dose group, respectively. OGTT test was performed 10 weeks after administration. At the 16th week of anesthesia, specimens were taken and executed. Determination of short chain fatty acids in rat feces by gas chromatography. The fecal flora of rats was detected by MiSeq 16s-rDNA. The results of the study are as follows: 1. Lilarubicin can affect the abundance of intestinal flora to a certain extent, and the abundance of intestinal flora is further reduced by using Lilaruin in diabetic rats. Lilarubicin increased the content of short chain fatty acids in feces of diabetic rats. It was found that a high content of anti-glycopeptide bacteria was found in the fecal specimens of the model group. The scientific name Ruminococcus gauvreauii, was significantly different from that of the blank group, the low dose group and the high dose group. Conclusion Lilarubicin is negatively correlated with the abundance of intestinal flora in diabetic rats and positively correlated with the metabolites of flora (short chain fatty acids). Such results may be associated with the effect of Lilaruin on gastrointestinal function. The proportion of an antiglycopeptide Ruminococcus gauvreauii in the intestinal flora of ALX diabetic rats was increased, but decreased in the group treated with Lilarupeptide, but not detected in the blank group of normal rats, which may be related to the effect of GLP-1.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R587.1

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