GLP-1对STZ诱导AD模型保护作用
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摘要
目的通过侧脑室给予GLP-1,观察其对侧脑室注射STZ诱导的AD动物模型的保护作用:GLP-1对STZ诱导的实验动物行为学损伤的保护作用;GLP-1对STZ诱导的实验动物血清和脑组织AB表达的作用,进而回答GLP-1可能的AD保护作用。
方法体重230g～250g的成年雄性Wister大鼠,经过一周的适应性饲养后,排除体质相对较差(食欲较差,体重明显下降)大鼠。应用Morris水迷宫进行初筛,去除先天痴呆(潜伏期平均值＞50 s)和游泳姿势不良者。将剔除死亡和不合实验要求动物后的合格大鼠随机分为三组:空白对照组、模型组和GLP-1保护组,每组10只。通过侧脑室注射,模型组给予10%STZ,GLP-1保护组10%STZ+GLP-1,空白对照组给予相同体积的生理盐水。抗生素处理伤口后,分别于术后第7天、第14天和第21天抽取大鼠尾静脉血,应用不饱和竞争放射免疫法测定血清Aβ水平。各组大鼠于侧脑室注射前及注射后21天进行7天Morris水迷宫测试其行为学变化。动物处死后,取脑组织做Aβ免疫组化,检测其脑内Aβ的变化。
结果(1)STZ处理损伤实验动物学习能力,延长潜伏期时间,GLP-1逆转STZ这一作用,使实验动物潜伏期缩短到接近正常组水平(两组间P＞0.05)。
(2)STZ处理损伤实验动物记忆,减少实验动物通过去除逃避平台后经过该平台的次数。GLP-1逆转STZ这一作用,使实验动物经过逃避平台次数接近正常组水平(两组间P＞0.05)。
(3)STZ处理诱导实验动物增高血清Aβ水平,GLP-1逆转增高的Aβ。
(4)STZ处理诱导实验动物增加大鼠大脑皮层Aβ免疫组化染色密度。GLP-1逆转STZ的这一作用,使大脑皮层Aβ免疫组化染色密度降至接近正常水平。
结论GLP-1逆转STZ侧脑室注射诱导的实验动物行为学损伤和血清及大脑皮层Aβ的增加,显示出其具有一定的AD保护作用。
Propose:To investigate GLP-1 's protection function to AD animal model induced by STZ.The study aim is:(1)effect of GLP-1 on behavior of rats treated by STZ;(2) effect of GLP-1 on Aβin serum and brain of rats treaded by STZ.
Method:Male Wister rats were fed for a week and the weaker ones,which have a bad appetite or lost weight quickly,were excluded.Then 30 qualified rats were left after the choice of Morris water maze,through which the Down's syndromes(the average of incubation period is over 50s) and the ones which didn't swim well were excluded.The 30 qualified rats were divided into three groups:black comparison group,AD model group and GLP-1 protected group.There are 10 rats in each group respectively.The rats in AD model group were injected 10%STZ through head,and GLP-1 group 10%STZ and GLP-1,while the black comparison group only Physiological Saline.The wound was managed treated with antibiotic.7 days,14 days and 21 days respectively after the operation,vein blood of the rats was draw and the level of serum was tested by unsaturated radioimmunoassay.The behavior of the rats before and 21 days after the Morris water maze test were compared.After putting the rats to death,the changes of Aβin their brain organization were tested.
Results:(1) The avoiding latent period of rats treated by STZ was delayed as compared with control rats.GLP-1 reversed the damage of STZ to shorten latent period of rats compared with the rats treated by STZ.
(2) The rats of control swam more in the area where the platform had installed compared with the rats treated by STZ.The rats treated by GLP-1 swam more in the area where the platform had installed compared with the rats treated by STZ.
(3) Serum Aβof rats treated by STZ was obviously elevated as compared with control rats and the rats treated by GLP-1.
(4) More immune staining neurons were seen in the brain of rats treated by STZ as compared with control rats and the rats treated by GLP-1.
Conclusion:GLP-1 improved bahavior damaged by STZ,decreaded serum Aβinduced by STZ and weaken Aβexpression in brain induced by STZ.It is possible for GLP-1 to improve AD-like behavior and pathology.
方法体重230g～250g的成年雄性Wister大鼠,经过一周的适应性饲养后,排除体质相对较差(食欲较差,体重明显下降)大鼠。应用Morris水迷宫进行初筛,去除先天痴呆(潜伏期平均值＞50 s)和游泳姿势不良者。将剔除死亡和不合实验要求动物后的合格大鼠随机分为三组:空白对照组、模型组和GLP-1保护组,每组10只。通过侧脑室注射,模型组给予10%STZ,GLP-1保护组10%STZ+GLP-1,空白对照组给予相同体积的生理盐水。抗生素处理伤口后,分别于术后第7天、第14天和第21天抽取大鼠尾静脉血,应用不饱和竞争放射免疫法测定血清Aβ水平。各组大鼠于侧脑室注射前及注射后21天进行7天Morris水迷宫测试其行为学变化。动物处死后,取脑组织做Aβ免疫组化,检测其脑内Aβ的变化。
结果(1)STZ处理损伤实验动物学习能力,延长潜伏期时间,GLP-1逆转STZ这一作用,使实验动物潜伏期缩短到接近正常组水平(两组间P＞0.05)。
(2)STZ处理损伤实验动物记忆,减少实验动物通过去除逃避平台后经过该平台的次数。GLP-1逆转STZ这一作用,使实验动物经过逃避平台次数接近正常组水平(两组间P＞0.05)。
(3)STZ处理诱导实验动物增高血清Aβ水平,GLP-1逆转增高的Aβ。
(4)STZ处理诱导实验动物增加大鼠大脑皮层Aβ免疫组化染色密度。GLP-1逆转STZ的这一作用,使大脑皮层Aβ免疫组化染色密度降至接近正常水平。
结论GLP-1逆转STZ侧脑室注射诱导的实验动物行为学损伤和血清及大脑皮层Aβ的增加,显示出其具有一定的AD保护作用。
Propose:To investigate GLP-1 's protection function to AD animal model induced by STZ.The study aim is:(1)effect of GLP-1 on behavior of rats treated by STZ;(2) effect of GLP-1 on Aβin serum and brain of rats treaded by STZ.
Method:Male Wister rats were fed for a week and the weaker ones,which have a bad appetite or lost weight quickly,were excluded.Then 30 qualified rats were left after the choice of Morris water maze,through which the Down's syndromes(the average of incubation period is over 50s) and the ones which didn't swim well were excluded.The 30 qualified rats were divided into three groups:black comparison group,AD model group and GLP-1 protected group.There are 10 rats in each group respectively.The rats in AD model group were injected 10%STZ through head,and GLP-1 group 10%STZ and GLP-1,while the black comparison group only Physiological Saline.The wound was managed treated with antibiotic.7 days,14 days and 21 days respectively after the operation,vein blood of the rats was draw and the level of serum was tested by unsaturated radioimmunoassay.The behavior of the rats before and 21 days after the Morris water maze test were compared.After putting the rats to death,the changes of Aβin their brain organization were tested.
Results:(1) The avoiding latent period of rats treated by STZ was delayed as compared with control rats.GLP-1 reversed the damage of STZ to shorten latent period of rats compared with the rats treated by STZ.
(2) The rats of control swam more in the area where the platform had installed compared with the rats treated by STZ.The rats treated by GLP-1 swam more in the area where the platform had installed compared with the rats treated by STZ.
(3) Serum Aβof rats treated by STZ was obviously elevated as compared with control rats and the rats treated by GLP-1.
(4) More immune staining neurons were seen in the brain of rats treated by STZ as compared with control rats and the rats treated by GLP-1.
Conclusion:GLP-1 improved bahavior damaged by STZ,decreaded serum Aβinduced by STZ and weaken Aβexpression in brain induced by STZ.It is possible for GLP-1 to improve AD-like behavior and pathology.
引文
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