5-HT對(duì)糖尿病小鼠胰腺和腸系膜動(dòng)脈功能的調(diào)節(jié)作用機(jī)制研究
發(fā)布時(shí)間:2018-05-12 08:12
本文選題:糖尿病 + 胰腺動(dòng)脈; 參考:《浙江大學(xué)》2017年碩士論文
【摘要】:目的:糖尿病是一種以糖代謝紊亂為主要特征的臨床常見內(nèi)分泌疾病。其后期有多種并發(fā)癥,其中最嚴(yán)重的是糖尿病血管病變。本論文主要研究糖尿病條件下,胰腺動(dòng)脈和腸系膜動(dòng)脈對(duì)5-HT的反應(yīng)性變化,以及一氧化氮在其中的作用機(jī)制。方法:C57B1/6雄性小鼠60只,約12周齡,體重25-27克,隨機(jī)分為對(duì)照組(C57B1組)和糖尿病組(DM組)。DM組小鼠通過(guò)給予腹腔注射鏈脲佐菌素(80mg/kg/d)連續(xù)四天,構(gòu)建小鼠糖尿病模型;腹腔注射等體積檸檬酸-檸檬酸鈉的C57BL/6小鼠作為正常對(duì)照組。1.采用微血管張力測(cè)定系統(tǒng)測(cè)定兩組小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈對(duì)不同濃度的5-HT、AngⅡ的反應(yīng)性,并測(cè)定血管張力的變化。2.使用5-HT2A受體激動(dòng)劑DOI、5-HT1B/1D受體激動(dòng)劑Sumatriptan和5-HT2B受體激動(dòng)劑BW723C86,分別刺激小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈,并測(cè)定其血管張力值的變化。3.使用eNOS抑制劑L-NAME對(duì)血管預(yù)處理,然后用5-HT刺激胰腺動(dòng)脈和腸系膜動(dòng)脈,測(cè)定器血管張力變化。4.使用NE對(duì)血管預(yù)收縮,然后觀察胰腺動(dòng)脈和腸系膜動(dòng)脈對(duì)SNP的反應(yīng)。5.采用實(shí)時(shí)熒光定量PCR的方法,檢測(cè)胰腺動(dòng)脈和腸系膜動(dòng)脈中eNOS、5-HT1B、5-HT1D、5-HT2A、5-HT2B受體的mRNA水平。6.采用酶聯(lián)免疫法,檢測(cè)血漿中5-HT的濃度,以及胰腺動(dòng)脈和腸系膜動(dòng)脈中eNOS的濃度水平。結(jié)果:1.與對(duì)照組相比,糖尿病小鼠血漿中5-HT濃度明顯升高。2.與對(duì)照組相比,糖尿病小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈對(duì)5-HT的收縮均呈現(xiàn)明顯減弱趨勢(shì),而對(duì)Ang Ⅱ的收縮無(wú)明顯差異。3.糖尿病組小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈對(duì)DOI、Sumatriptan、BW723C86的收縮作用也明顯弱于對(duì)照組,并具有顯著性差異。4.使用L-NAME抑制eNOS的活性后,糖尿病組小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈的反應(yīng)也都恢復(fù)到與對(duì)照組相似的水平。5.兩組小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈對(duì)SNP的反應(yīng)均無(wú)明顯差異。6.糖尿病條件下,胰腺動(dòng)脈和腸系膜動(dòng)脈eNOS、5-HT1B、5-HT1D、5-HT2A、5-HT2B受體的mRNA水平與對(duì)照組無(wú)明顯差異。7.與對(duì)照組相比,糖尿病小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈eNOS的濃度有減少的趨勢(shì),但沒有顯著性差異。結(jié)論:糖尿病小鼠胰腺動(dòng)脈和腸系膜動(dòng)脈對(duì)5-HT的收縮反應(yīng)減弱,其機(jī)制可能是由于5-HT受體活性減弱,同時(shí)激活了內(nèi)皮型一氧化氮合酶(eNOS),造成NO釋放增多,血管相對(duì)舒張。
[Abstract]:Objective: diabetes mellitus is a common endocrine disease characterized by glucose metabolism disorder. There are a variety of complications in the later stage, the most serious of which is diabetic vascular disease. In this paper, we studied the changes of the responsiveness of pancreatic artery and mesenteric artery to 5-HT in diabetic rats and the mechanism of nitric oxide acting on it. Methods Sixty male mice, about 12 weeks old, weighing 25-27 g, were randomly divided into control group (C57B1 group) and diabetic group (DM group). Mice in DM group were given intraperitoneal injection of streptozotocin 80 mg / kg / d for four days to establish diabetic model. C57BL/6 mice of equal volume citric acid and sodium citrate were injected intraperitoneally as normal control group. The reactivity of pancreatic artery and mesenteric artery to different concentrations of 5-HT Ang 鈪,
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