二甲雙胍對DM大鼠血漿VSFT水平和胰島素抵抗功能的影響
發(fā)布時間:2018-03-31 04:29
本文選題:內(nèi)臟脂肪素 切入點:二甲雙胍 出處:《蘭州大學》2014年碩士論文
【摘要】:[目的]1、探索連續(xù)小劑量STZ注射復制糖尿病(DM)模型的可行性;2、研究二甲雙胍對DM大鼠血漿內(nèi)臟脂肪素(VSFT)水平的影響;3、探討內(nèi)臟脂肪素對胰島素抵抗(IR)作用的初步機制。 [方法]Wistar大鼠45只,正常飼養(yǎng)1周后,按隨機數(shù)表示法分為正常對照組(NC,n=15)和糖尿病模型組(n=30)。糖尿病模型組30只大鼠經(jīng)過連續(xù)5天腹腔注射小劑量(30mg/kg) STZ,3天和14天后檢測隨機血糖,以隨機血糖濃度超過16.7mmol/L者為模型復制成功。正常組15只大鼠根據(jù)體重劑量連續(xù)5天腹腔注射檸檬酸緩沖液(PH=4.5),隨后將這30只大鼠再分為糖尿病模型組(DM,n=15)和二甲雙胍干預組(MET, n=15).干預組選用二甲雙胍作為干預藥物,藥量200mg·kg-1·d-1灌胃;糖尿病模型組和正常對照組灌胃采用SPF級實驗室里面的大鼠常規(guī)飲水。三組再同步飼養(yǎng)5周,每周做好檢測和記錄血糖及體重的工作。模型復制成功5周后,將各組大鼠禁食12h,水合氯醛麻醉后,頸靜脈取血,血液以4000轉(zhuǎn)離心,將離心后的血漿液氮速凍并轉(zhuǎn)移到-80℃保存,用于檢測血漿VSFT及相關指標等;留取并固定部分肝臟,用于組織學形態(tài)檢測。 [結果]1、持續(xù)小劑量STZ注射可以復制出糖尿病模型,且更接近T2DM型;該大鼠模型發(fā)生糖脂代謝紊亂;存在較高的胰島素抵抗;能夠很好的保持高血糖癥狀態(tài)至少5周時間;肝臟發(fā)生明顯的病理變化。2、對比STZ復制糖尿病模型的其他方法,本方法成功率高;模型復制后動物死亡率低;雌鼠模型復制成功率較雄鼠高;而且模型復制成功后雌鼠的體重消瘦情況較雄鼠明顯;模型復制后體重較輕的動物易死亡。3、二甲雙胍可以增高DM鼠體重(P0.05)。4、二甲雙胍可以降低DM鼠血漿VSFT濃度(P0.05),消弱胰島素抵抗(P0.05)、消減糖脂代謝紊亂(P0.05)、減輕DM大鼠肝臟受損情況。5、VSFT與體重正相關關系表現(xiàn)在正常大鼠中。6、VSFT與IR正相關性及其與體重的負相關性在DM大鼠身上表現(xiàn)(P0.05)。 [結論]1、持續(xù)小劑量STZ注射可復制出DM大鼠模型;2、二甲雙胍可降低DM大鼠的VSFT水平,消減胰島素抵抗;3、VSFT與胰島素抵抗及體重相關。
[Abstract]:[objective] 1. To explore the feasibility of continuous low dose STZ injection to induce diabetes mellitus (DM) model, to study the effect of metformin on plasma visceral adipoxin (VSFT) level in diabetic rats and to explore the mechanism of visceral lipopolipin on insulin resistance (IRR). [methods] Forty-five Wistar rats were randomly divided into two groups: control group (n = 45) and diabetic model group (n = 30). After 5 consecutive days of intraperitoneal injection of 30 mg 路kg ~ (-1) STZ for 3 days and 14 days, the blood glucose levels were measured in the diabetic model group (n = 30) and the control group (n = 30), respectively, after 1 week of normal feeding, the rats were randomly divided into two groups: the control group (n = 30) and the diabetic model group (n = 30). 15 rats in the normal group were injected citric acid buffer for 5 days according to their body weight. The 30 rats were then divided into diabetic model group (n = 15) and metformin group (n = 15), after which 30 rats were divided into diabetic model group (n = 15) and metformin group (n = 15), after which 30 rats were divided into diabetic model group (n = 15) and metformin group (n = 15). Metformin was used as the intervention drug in the intervention group. The rats in the diabetic model group and the normal control group were given regular drinking water in the SPF laboratory. The three groups were fed simultaneously for 5 weeks, and the blood glucose and body weight were measured and recorded every week. Blood was taken from jugular vein after fasting for 12 hours, blood was collected from jugular vein, blood was centrifuged at 4000 turns, and the plasma was frozen and transferred to -80 鈩,
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