GLP-1类似物对糖尿病大鼠认知功能障碍的影响

发布时间：2018-05-05 00:13

  本文选题：GLP-1类似物 + 链脲佐菌素　； 参考：《福建医科大学》2015年硕士论文

【摘要】：目的:现今,糖尿病与神经退行性疾病之间的关系日益受到关注。GLP-1类似物目前主要是用于2型糖尿病的治疗,其神经保护作用也逐渐受到广泛关注。本文探讨胰高血糖素样肽-1(Glucagon-like peptide-1,GLP-1)类似物艾塞那肽(Exenatide)对链脲佐菌素(Streptozotocin,STZ)所诱导的糖尿病大鼠相关认知功能障碍的改善作用及其可能的机制。方法:将健康的雄性SD大鼠适应性喂养1周后,随机分成正常对照组(NC组)和糖尿病模型组。糖尿病模型组采用高脂高糖饲料喂养4周后,腹腔注射小剂量的STZ(30mg/kg)建立糖尿病模型,正常对照组给予腹腔注射相应剂量的柠檬酸钠缓冲液。腹腔注射STZ 3天后检测大鼠尾静脉随机血糖,血糖值≥16.7mmol/l者,视为造模成功。将造模成功的SD大鼠随机分成糖尿病组(DM组)及Exenatide干预组(Ex+DM组),Ex+DM组的大鼠皮下注射Exenatide(3μg/kg,bid),DM组给予皮下注射生理盐水对照,连续干预16周,给药期间观察大鼠摄食、饮水情况,每周测一次体重和血糖。给药结束后,应用Morris水迷宫检测大鼠的认知功能;采血检测大鼠的血糖、血脂情况;每组取部分大鼠用4%多聚甲醛灌注后取海马组织行光镜和电镜检查,观察大鼠海马的形态学变化。剩余大鼠新鲜海马组织于-80℃超低温冰箱保存,Western Blot法测定磷酸化tau蛋白p-tau(s202)、p-tau(s396)等蛋白的表达水平;测定氧化应激相关指标丙二醛(Malondialdehyde,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-PX)以进行机制探讨。结果:1实验过程中,可观察到DM组大鼠的摄食量、饮水量较NC组多,Ex+DM组在给药期间,其摄食量、饮水量较DM组大鼠少,Exenatide干预16周后Ex+DM组体重较NC组、DM组减轻(P0.05)。2 Morris水迷宫实验结果显示与NC组相比,DM组大鼠逃避潜伏期明显延长(P0.05),穿过原平台位置的次数明显减少(P0.05),而给予Exenatide干预的Ex+DM组与DM组相比则有明显改善(P0.05);3大鼠血糖、血脂检查结果:DM组、Ex+DM组血糖均显著高于NC组(P0.05);胆固醇(TC)、甘油三酯(TG)在DM组中均高于NC组与Ex+DM组,差异有统计学意义(P0.05)。4各组大鼠海马HE染色及电镜结果:光镜和电镜结果显示DM组大鼠海马组织结构出现异常,而Ex+DM组大鼠中海马结构异常情况得到一定的改善。5海马组织磷酸化tau蛋白测定结果显示,与NC组相比,DM组p-tau(s202)及p-tau(s396)蛋白的表达量明显增多(P0.05);给予Exenatide干预的Ex+DM组与DM组相比则磷酸化tau蛋白明显降低(P0.05)。6海马组织氧化应激结果显示:与NC组相比,DM组MDA含量显著增高,SOD及GSH-PX活性显著降低(P0.05);与DM组相比,Ex+DM组MDA含量显著减少,SOD及GSH-PX活性显著增高(P0.05)结论:GLP-1类似物Exenatide能够改善糖尿病大鼠的认知功能障碍,其改善作用可能与其对海马组织中氧化应激的影响有关。
[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，

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