咪多吡对帕金森病模型大鼠黑质纹状体胶质细胞增生及活化的影响

Influence of eldepryl in proliferation and activation of gliacytes in substantia nigra and striatum in rats with Parkinson's disease

目的:探讨咪多吡对帕金森病(PD)模型大鼠黑质纹状体胶质纤维酸性蛋白(GFAP)和整合素αM(cd11b)表达的影响,阐明咪多吡对胶质细胞的调控作用。方法:72只健康SD大鼠随机分为对照组、PD模型组(模型组)和咪多吡处理组(咪多吡组),每组24只。PD模型组和咪多吡组大鼠采用鱼藤酮制备PD模型,模型制备成功后各组大鼠随机分为4d和8d2个亚组,每个亚组12只大鼠。免疫组织化学法和Western blotting法检测大鼠黑质纹状体GFAP和cd11b阳性细胞数和蛋白表达水平。结果:对照组大鼠GFAP和cd11b阳性细胞均处于静息状态,GFAP阳性细胞胞体细长不规则,有细长的突起,cd11b阳性细胞胞体较小,呈分支状,突起较细长;模型组大鼠GFAP和cd11b阳性细胞呈激活状态,GFAP阳性细胞胞体肥大,突起增多增粗,cd11b阳性细胞胞体增大,突起变粗变短,数量增多;与模型组比较,咪多吡组大鼠GFAP阳性细胞胞体及突起较细长,cd11b阳性细胞胞体较小,突起较细长,数量减少。对照组大鼠黑质纹状体可见少量的GFAP和cd11b阳性细胞表达,8d组与4d组比较差异无统计学意义(P>0.05);模型组大鼠GFAP和cd11b阳性细胞数和蛋白表达水平均明显增加,与对照组比较差异均有统计学意义(P<0.01),且8d组多于4d组,但差异无统计学意义(P>0.05);咪多吡组大鼠GFAP和cd11b阳性细胞数和蛋白表达水平均明显降低,与模型组比较差异均有统计学意义(P<0.01),且8d组少于4d组,2组比较差异有统计学意义(P<0.05)。结论:PD模型大鼠黑质纹状体胶质细胞明显增生和活化,咪多吡能够抑制胶质细胞的增生和活化。

Objective To discuss the influence of eldepryl on the expressions of glial fibrillary acidic protein （GFAP） and cd11b in substantia nigra and striatum in the rats with Parkinson’s disease （PD）,and to clarify the regulatory role of eldepryl in the gliacytes.Methods 72 SD rats were randomly divided into control group,PD model group and eldepryl group,and each group was divided randomly into 4 d and 8 d subgroups （n=12）after the success of model preparation.The PD rat models were established by injecting rotenone in subcutaneous.The number of GFAP and cd11b positive cells and the expressions of GFAP and cd11b were detected by immunohistochemistry and Western blotting method.Results The GFAP and cd11b positive cells were all in a resting state in control group, the GFAP-positive cell body was slender and irregular and had elongated protrusions;the cd1 1 b-positive cell body was small and branch-like,and it had more slender protrusions.The GFAP and cd11b positive cells were all in a active state in model group, the GFAP-positive cell body was hypertrophy, the proj ections increased thickening;the cd1 1 b-positive cell body was more bigger, the proj ections were shorter and thicker, and the number was increased.Compared with model group, the GFAP-positive cell body and protrusions were more slender, the CD11b-positive cell body was more smaller,the projections were more slender,and the number was decreased in eldepryl group.There were a small amount of expression of GFAP and cd11b positive cells in substantia nigra and striatum in the rats in control group,and there was no significant difference between 8 d group and 4 d group（P＆gt;0.05）. The number of GFAP and cd11b positive cells and the protein expression levels were significantly increased in model group compared with control group（P〈0.01）;there was more expression in 8 d group compared with 4 d group,but there was no significant difference（P＆gt;0.05）.The number of GFAP and cd11b positive cells and the protein expression levels in eldepryl group were significantly reduced compared with model group（P〈0.01）;there were less expression in 8 d group compared with 4 d group, and there was significant difference （P〈0.05 ）. Conclusion There are activation and proliferation of the gliacytes in substantia nigra and striatum in the rats with PD,and eldepryl can inhibit the activation and proliferation of gliacytes.