本文選題：GLP-1類似物 + 鏈脲佐菌素��； 參考：《福建醫(yī)科大學》2015年碩士論文

【摘要】：目的:現(xiàn)今,糖尿病與神經退行性疾病之間的關系日益受到關注。GLP-1類似物目前主要是用于2型糖尿病的治療,其神經保護作用也逐漸受到廣泛關注。本文探討胰高血糖素樣肽-1(Glucagon-like peptide-1,GLP-1)類似物艾塞那肽(Exenatide)對鏈脲佐菌素(Streptozotocin,STZ)所誘導的糖尿病大鼠相關認知功能障礙的改善作用及其可能的機制。方法:將健康的雄性SD大鼠適應性喂養(yǎng)1周后,隨機分成正常對照組(NC組)和糖尿病模型組。糖尿病模型組采用高脂高糖飼料喂養(yǎng)4周后,腹腔注射小劑量的STZ(30mg/kg)建立糖尿病模型,正常對照組給予腹腔注射相應劑量的檸檬酸鈉緩沖液。腹腔注射STZ 3天后檢測大鼠尾靜脈隨機血糖,血糖值≥16.7mmol/l者,視為造模成功。將造模成功的SD大鼠隨機分成糖尿病組(DM組)及Exenatide干預組(Ex+DM組),Ex+DM組的大鼠皮下注射Exenatide(3μg/kg,bid),DM組給予皮下注射生理鹽水對照,連續(xù)干預16周,給藥期間觀察大鼠攝食、飲水情況,每周測一次體重和血糖。給藥結束后,應用Morris水迷宮檢測大鼠的認知功能;采血檢測大鼠的血糖、血脂情況;每組取部分大鼠用4%多聚甲醛灌注后取海馬組織行光鏡和電鏡檢查,觀察大鼠海馬的形態(tài)學變化。剩余大鼠新鮮海馬組織于-80℃超低溫冰箱保存,Western Blot法測定磷酸化tau蛋白p-tau(s202)、p-tau(s396)等蛋白的表達水平;測定氧化應激相關指標丙二醛(Malondialdehyde,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽過氧化物酶(Glutathione peroxidase,GSH-PX)以進行機制探討。結果:1實驗過程中,可觀察到DM組大鼠的攝食量、飲水量較NC組多,Ex+DM組在給藥期間,其攝食量、飲水量較DM組大鼠少,Exenatide干預16周后Ex+DM組體重較NC組、DM組減輕(P0.05)。2 Morris水迷宮實驗結果顯示與NC組相比,DM組大鼠逃避潛伏期明顯延長(P0.05),穿過原平臺位置的次數(shù)明顯減少(P0.05),而給予Exenatide干預的Ex+DM組與DM組相比則有明顯改善(P0.05);3大鼠血糖、血脂檢查結果:DM組、Ex+DM組血糖均顯著高于NC組(P0.05);膽固醇(TC)、甘油三酯(TG)在DM組中均高于NC組與Ex+DM組,差異有統(tǒng)計學意義(P0.05)。4各組大鼠海馬HE染色及電鏡結果:光鏡和電鏡結果顯示DM組大鼠海馬組織結構出現(xiàn)異常,而Ex+DM組大鼠中海馬結構異常情況得到一定的改善。5海馬組織磷酸化tau蛋白測定結果顯示,與NC組相比,DM組p-tau(s202)及p-tau(s396)蛋白的表達量明顯增多(P0.05);給予Exenatide干預的Ex+DM組與DM組相比則磷酸化tau蛋白明顯降低(P0.05)。6海馬組織氧化應激結果顯示:與NC組相比,DM組MDA含量顯著增高,SOD及GSH-PX活性顯著降低(P0.05);與DM組相比,Ex+DM組MDA含量顯著減少,SOD及GSH-PX活性顯著增高(P0.05)結論:GLP-1類似物Exenatide能夠改善糖尿病大鼠的認知功能障礙,其改善作用可能與其對海馬組織中氧化應激的影響有關。
[Abstract]:Objective: nowadays, the relationship between diabetes mellitus and neurodegenerative diseases has attracted more and more attention. GLP-1 analogue is mainly used in the treatment of type 2 diabetes, and its neuroprotective effect has been paid more and more attention. The aim of this study was to investigate the effect of glucagon-like peptide-1 (Glucagon-like peptide-1 GLP-1) analogue, Exenatide), on the improvement of cognitive impairment induced by streptozotocinn (STZZ) in diabetic rats and its possible mechanism. Methods: healthy male Sprague-Dawley rats were randomly divided into normal control group (NC group) and diabetic model group after one week of adaptive feeding. The diabetic model group was fed with high fat and high sugar diet for 4 weeks, and the diabetic model was established by intraperitoneal injection of 30 mg / kg STZ. The normal control group was given the corresponding dose of sodium citrate buffer. The random blood glucose of caudal vein of rats was detected 3 days after intraperitoneal injection of STZ. Those whose blood glucose value was 鈮，

本文編號：1845312