硼替佐米对脑缺血再灌注损伤保护作用的研究

目的 观察硼替佐米对脑缺血再灌注后炎性反应及细胞凋亡的影响,探讨其脑保护作用机制.方法 将15只大鼠随机分为假手术组、生理盐水组、硼替佐米组各5只.脑缺血2 h再灌注即刻给予硼替佐米0.2 mg/kg尾静脉注射,对照组以等量生理盐水尾静脉注射,再灌注后24 b取材.免疫组化法测组织核因子(NF)-κBp65、白细胞介素(IL)-1β;缺口末端标记法检测神经细胞凋亡.结果假手术组偶见NF-κBp65、IL-1β免疫反应阳性细胞分别为(1.21±0.16)个/400倍、(11.56±0.99)个/400倍],凋亡细胞亦少见(2.88±0.27)个/400倍],生理盐水组与硼替佐米组均可见大量NF-κBp65、IL-1β免疫反应阳性细胞及凋亡细胞分别为(56.28±1.95)个/400倍与(29.76±2.53)个/400倍、(47.64±2.06)个/400倍与(29.6±1.61)个/400倍、(51.05±4.23)个/400倍与(33.44±2.06)个/400倍],差异有统计学意义(均P＜0.05).结论 蛋白酶体抑制剂硼替佐米可通过减少NF-κB的激活,抑制炎性反应,减少细胞凋亡,对缺血脑组织有保护作用.

Protective effect of velcade on ischemia-reperfusion injury in rat brain

Objective To observe the effects of velcade on inflammatory reaction and cell apoptosis after ischemia-reperfusion injury, and to explore the neuroprotective mechanism of velcade.Methods The 15 male Wistar rats were randomly divided into sham-operated group, physiological saline control group and velcade-treated group (n= 5, each). The model of temporary middle cerebral artery occlusion (MCAO) was applied and reperfused after 2 hours. Immediately after the reperfusion, all rats were performed intraperitoneal injection with velcade 0. 2 mg/kg in velcadetreated group, and with the same volume of physiological saline in control group. After 24 hours, the rats were decapitated in all groups. The apoptosis cells were found by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the expressions of nuclear factor-κBp65 (NF-κBp65) and interleukinh-1β (IL-1β) were detected by immunohistochemistry. Results The immunologically positive cells of NF-κBp65, IL-1β and apoptosis cells were occasionally found in shamoperated group (1.21 ± 0. 16)/400 power, (11.56 ± 0. 99)/400 power and (2. 88 ± 0. 27)/400 power], while a lot of immunologically positive cells of NF-κBp65, IL-1β and apoptosis cells were found in velcade-treated group and control group. The control with compared group, these cells were significantly more in the velcade-treated group (56.28± 1.95)/400 power vs. (29. 76±2.53)/400 power, (47. 64±2.06)/400 power vs. (29.6±1. 61)/400 power and (51. 05±4. 23)/400 power vs.(33.44±2.06)/400 power, all P＜0. 05]. Conclusions The velcade could decrease the expressions of the NF-κBp65 and IL-1β and diminish the neuronal apoptosis. The neuroprotective mechanism of velcade may lie in decreasing apoptosis through inhibiting inflammation.