甲基苯丙胺中毒大鼠纹状体COX-2、PGE2、EP2受体及小胶质细胞表达的研究

摘要

Objective: To investigate the relationship of COX-2/PGE2 system and the raicroglia activation in the metham-phetamine intoxication rats by investigating the expression of COX-2, PGE2, EP: receptor and microglia in rats' striatum of metham-phetamine intoxication. Methods: 40 male Sprague-Dawley rats were randomly divided into control group(n=10) and experimental group (dividing it into the first, second and third group after the last injection, n= 10). Rats in the experimental group were intraperitoneal injected with methamphetamine hydrochloride (l0mg/kg), while those in the control group were injected with saline with the same volume (twice a day at 8:00 and 20:00 respectively for 4 continuous days ). Then the protein expression of COX-2, EP2 receptor and Ibal of intoxication rats in striatum was detected by immunohistochemistry technique and the test results were analyzed by image; PGE2 was examined by ELISA. Results: There was the expression of COX-2, PGE;, EP2 receptor and microglia in each group. The expression of COX-2, PGE2 and EP2 receptor reduced by varying degree at the first day compared with that in the control group. The expression of COX-2 began to rise and the expression of PGE2 and EP2 receptor still stay a low level at the second day. At the third day,the expression of COX-2 was higher than that in the control group and the expression of PGE2 and EP2 receptor became close to the control group. The expression of microglia was higher than that in the control group in the 3 experimental group, and the 3d group was higher than the 2d group, the 2d group was higher than the 1d group. Conclusion: There was no relationship between the COX-2/PGE2 system and the microglia activation; There was a close relationship between COX-2 and MA neurotoxicity.%目的:通过研究COX-2、PGE2、EP2受体及小胶质细胞在甲基苯丙胺中毒大鼠纹状体内的表达变化探讨甲基苯丙胺中毒大鼠纹状体中COX-2/PGE2系统与小胶质细胞活化之间的关系.方法:将40只健康成年雄性SD大鼠,随机分成对照组10只和实验组30只(实验组分成三个亚组,分为末次给药后1天组、2天组和3天组,n=10).实验组给予10mg,kg的MA腹腔注射,对照组给予同样剂量的生理盐水,每天注射两次,注射时间为8:00、20:00,连续注射4天.分别于末次给药后的第1天、第2天、第3天处杀.用免疫组化技术对中毒大鼠纹状体(CPU)中COX-2、EP2受体及Ibal(钙离子接头蛋白,小胶质细胞内一种特异性标记物)的表达进行检测,并进行图像分析.另外,取大鼠的纹状体运用酶联免疫法检测PGE2的含量.结果:COX-2、PGE2、EP2受体及小腔质细胞在各组均有表达.与对照组相比,实验组中:COX-2、PGE2、EP2受体的1天组表达均不同程度下降；2天组中COX-2表达水平大幅度上升,PGE2、EP2受体表达仍低于正常水平；3天组COX-2表达水平继续升高,而PGE2、EP2受体表达趋于正常组水平.而小胶质细胞表达水平则是三个实验组均高于正常组,且3天组高于2天组,2天组高于1天组.对照组与实验组有显著性差异(P＜0.05).结论:COX-2/PGE2系统与甲基苯丙胺中毒大鼠纹状体内小胶质细胞活化无明显相关性；COX-2与甲基苯丙胺的神经毒性有关.