蛋白酶体抑制剂诱导帕金森病大鼠模型海马区HSP70表达

Expression of HSP70 in the hippocampal area of rats with Parkinson disease induced by proteasome inhibitor lactacystin

目的观察蛋白酶体抑制剂Lactacystin诱导帕金森病大鼠模型海马区HSP70表达。方法将Lactacystin 10μg(2μl)经立体定向仪注射到大鼠(Lactacystin组,n=36)左侧黑质致密部,对照组(n=36)以等体积生理盐水代替;分别在药物注射后24h、3d、5d、7d、9d、11d、14d、18d和21d提取海马标本,通过免疫组化和RT-PCR观察HSP70的表达。结果Lactacystin组大鼠海马区HSP70表达较对照组高,表现为注药24h后表达开始增高,5d达高峰,11d开始减少;且海马区表达分布呈CA3>CA2>CA1。结论Lactacystin诱导帕金森病大鼠海马区HSP70表达增高,且呈明显区域性和时间依从性;增加的热休克蛋白可能参与拮抗蛋白酶体抑制毒性而起到神经细胞保护作用。

Objective To observe expression of HSP70 in the hippocampus of rat model of Parkinson disease （PD） induced by proteasome inhibitor Lactacystin. Methods Lactacystin of 10μg （2μl）, a selective proteasome inhibitor, was unilaterally injected stereotaxically into the left substantia nigra pars compacta of rats （n = 36）. Equal volume of saline was injected in the control group （n = 36）. After injection, hippocampal tissue was taken 24 h and 3, 5, 7d, 9, 11, 14, 18 and 21d after operation. The expression of HSP70 was observed in the hippocarnpus by immunohistochemistry and RT-PCR. Results The expression of HSP70 was higher in the Lactacystin group than in the control. The increase of the HSP70 expression occurred 24 h after the injection, and reached the peak in 5 d, then decreased but still higher than the control group 11d after the injection. Furthermore, the distribution of HSP70 in the hippocarnpal region presented as CA3 〉CA2 〉 CAl. Conclusion The expression of HSP70 is up-regulated in the hippocampus of rat models induced by proteasome inhibition Lactacystin, demonstrating significant regionality and time dependence, and the increased heat shock proteins may exert neuroprotection against Lactacystin-induced inhibition of proteasome.