蛋白酶体抑制剂万珂对脑缺血再灌注损伤保护作用机制的研究

Study of the Protective Effect on Proteasome Inhibitor VELCADE Against Cerebral Ischemia-reperfusion Injury

目的探讨万珂对脑缺血再灌注后细胞凋亡及线粒体的发生变化程度,探讨对脑缺血起到的保护作用。方法将实验于2012年5月—2013年12月期间选用的大鼠15只随机分为万珂治疗组5只、假手术组5只、生理盐水组5只。模型组马上进行万珂0.2 mg/kg尾静脉注射,对照组注射相同量的生理盐水,在24 h的时间点进行取材。免疫组化法测Cyt C、Caspase-3;神经细胞凋亡选择TUNEL法进行检测。结果假手术组凋亡细胞亦少见,偶见Cyt C、Caspase-3免疫反应阳性细胞,万珂组Cyt C、Caspase-3免疫反应阳性细胞及凋亡细胞明显减少,生理盐水组见大量上述细胞,且两组上述各项数据对比,差异有统计学意义,两组与假手术组上述各项数据对比,差异亦均有统计学意义。结论万珂是蛋白酶体抑制剂具有保护线粒体功能,明显的抑制炎症反应高峰形成,缩小脑梗死体积,减轻细胞凋亡,保护神经的作用。

Objective To observe the effects of VELCADE on cell apoptosis after cerebral ischemia-reperfusion and the level of mitochondrial changes and study on its protective effects to cerebral ischemia. Methods 15 laboratory rats from 2012 May to 2013 December were randomly divided into VELCADE groups and pseudo surgery group and saline group with 5 in each group. VEL-CADE groups received caudal vein injection of 0.2 mg/kg VELCADE and the control groups received saline injection of the same volume and experimental materials were collected after 24 h. Cyt C、Caspase-3 was detected by immunohistochemical and the neuronal apoptosis was detected by TUNEL. Results Fake surgery group apoptosis died cell also rare, occasionally Cyt c, and Cas-pase-3 immune reaction positive cell, VELCADE group Cyt c, and Caspase-3 immune reaction positive cell and the apoptosis died cell obviously reduced, saline group see large above cell, and two group above the data compared, differences significantly has statistics meaning, two group and fake surgery group above the data compared, differences also are has statistics meaning. Conclusion VELCADE is a proteasome inhibitor, and it has a protective function of mitochondria and can significantly inhibits the inflammatory response to peak form, reduces the volume of cerebral infarction and apoptosis, protects neural function.