摘要
目的:探讨原花青素(procyanidin,PC)对脑缺血再灌注后大鼠海马内质网应激(endoplasmic re-ticulum stress,ERS)相关分子表达的影响。方法:将180只SD大鼠随机分为假手术组、模型组和PC组,每组60只。PC组于术前1周灌胃给予PC(100 mg.kg-1)然后建立脑缺血再灌注模型,分别在脑缺血再灌注后3,6,12,24和48 h处死大鼠。观察不同时间点大鼠的神经行为表现;焦油紫染色处理大鼠海马组织切片,光镜观察病理学改变;末端标记法(TUNEL)检测细胞凋亡;采用免疫组化及RT-PCR方法检测脑缺血再灌注后不同时间点大鼠海马GRP78和CHOP的表达。结果:PC组大鼠脑缺血再灌注后的神经功能缺损明显改善,与模型组相比具有统计学差异(P<0.01),其细胞凋亡数亦明显少于模型组(P<0.05);模型组与假手术组相比,GRP78与CHOP明显升高(P<0.01),PC组GRP78表达高于模型组(P<0.05),而PC组CHOP表达低于模型组(P<0.05)。结论:PC对脑缺血再灌注损伤大鼠具有保护作用,其机制可能与其增加GRP78表达、拮抗CHOP表达、阻断内质网应激(ERS)启动的凋亡通路有关。
Objective: To investigate the effect of procyanidin(PC) on expressions of GRP78 and CHOP,the molecules related to endoplasmic reticulum stress(ERS),in hippocampus after cerebral ischemia-reperfusion(IR) in rats.Methods: SD rats(n=180) were divided into 3 groups(n=60 in each group).PC 100 mg·kg-1was administered by gavage for one week before surgery,and then the cerebral IR model was established.At 3,6,12,24 and 48 h after IR,neurological behavior score was observed.Paraffin sections of hippocampus were cut and stained with brilliant cresys violet to observe pathological changes.Apoptosis was detected by TdT-mediated dUTP nick end labeling(TUNEL),and the expression of GRP78 and CHOP were assayed by immunohistochemical staining and RT-PCR.Results: PC significantly improved neurological deficits(Bederson sore) as compared with IR control at each time point(P0.01).The number of apoptotic cells was significantly less in PC group than in IR control group(P0.05).The expressions of GRP78 and CHOP significantly increased after IR(P0.01).GPR78 expression was higher in PC group than in IR control group(P0.05).However,CHOP expression was less in PC group than in IR control group(P0.05).Conclusion: PC has a protective effect on cerebral IR injury,which may related to increased GRP78 and decreased CHOP expression,and to inhibition of the ERS-induced apoptosis pathway.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2011年第2期156-161,共6页
Chinese Journal of New Drugs
基金
辽宁省自然科学基金项目(20092192)
辽宁省教育厅高等学校科学研究项目(05L137)