Lactacystin诱导帕金森病大鼠黑质小胶质细胞、CD68和环氧化酶-2表达的变化  

Changes of microglia cells, CD68 and cyclooxygenase-2 expression in rat substantia nigra induced by lactacystin

作　　者：庄文欣[1] 陈丹丹[2,4] 付文玉[2] 袁丽[3] 朱勋[3] 于文辉[3] 刘丙新[3] 吴晓东[3] 

机构地区：[1]潍坊医学院 医学研究实验中心 [2]潍坊医学院 组织学与胚胎学教研室 [3]潍坊医学院 2008级临床医学专业,潍坊261053 [4]山东中医药高等专科学校解剖学生理学教研室

出　　处：《解剖学杂志》2012年第6期784-787,825,共5页Chinese Journal of Anatomy

基　　金：山东省自然科学基金（Y2008C129）;山东省医药卫生科技发展计划项目（2009HZ106）;潍坊医学院大学生科技创新基金重点项目（KX2009014）

摘　　要：目的：研究蛋白酶体抑制剂lactacysdn诱导大鼠黑质小胶质细胞的数量、活化程度的变化及环氧化酶-2（COX-2）的表达。方法：采用立体定向术将10肛glactacystin注射至大鼠黑质部位，免疫组织化学观察黑质区多巴胺能神经元和小胶质细胞数量、小胶质细胞活化程度（CD68）的变化及炎性介质COX-2的表达；RT-PCR方法检测THmRNA和CD68mR-NA的转录变化情况。结果：注射lactacystin3周后，阿扑吗啡腹腔注射诱导大鼠出现典型旋转行为；4周时模型组大鼠损毁侧黑质酪氨酸羟化酶（TH）阳性细胞数明显减少，黑质小胶质细胞数量增加，CD68和COX-2的表达均增强，与对照组相比，差异均有统计学意义。模型组THmRNA表达低于对照组，CD68mRNA表达高于对照组，差异均有统计学意义。结论：蛋白酶体抑制剂lactacystin能激活大鼠黑质小胶质细胞，诱导与炎症发生有关的CD68和COX2的表达。Objective： To investigate the changes of microglia and dopaminergic neurons and expression of cyclooxygenase-2 （COX-2） in rat substantia nigra induced by proteasome inhibitor lactacystiru Methods： Laetacystin, a selective proteasome inhibitor, was unilateral injected stereotaxically into the substantia nigra of rats. Immunohistochemistry was used to detect the changes in the neurons and microglial cells as well as the expressions of CD68 and COX-2 in the substantia nigra. The expression levels of TH mRNA and CD68 mRNA were examined by reverse transcription-polymerase chain reaction. Re- suits： Three weeks after injection of lactacystin, apomorphine intraperitoneal injection induced changes in typical behavior. At 4 weeks, tyrosine hydroxylase（TH） positive ceils in the substantia nigra lesioned side of the laetacystin group rats de- creased significantly. In the experimental group, microglial calls in the lesioned side significantly increased; and the optical density values of CD68 and COX-2 in the lesioned side of the substantia nigra increased. The expression levels of postopera- tive TH mRNA in the injected side midbrain of the lactacystin group were lower than those in the control group, and the ex- pression levels of postoperative CD68 mRNA in the injected side midbrain of the lactacystin group increased. Conelusion：Proteasome inhibitor lactacystin may cause microglia activation in rat substantia nigra and induce the expression of CD68 and COX-2 associated with inflammation in the substantia nigra.

关 键 词：LACTACYSTIN 帕金森病 黑质 小胶质细胞 CD68 环氧化酶-2 

分 类 号：R743.31[医药卫生—神经病学与精神病学]