葛根素衍生物对局灶性脑缺血再灌注的保护作用及对caspase-3表达的影响  

Neuroprotective effects of puerarin derivative on focal cerebral ischemia and reperfusion and its effect on expression of caspase-3 in rats

作　　者：张宏伟[1,2] 张帆[1] 董志[2] 朱毅[3] 

机构地区：[1]聊城市人民医院临床药学室,山东聊城252000 [2]重庆医科大学药学院生化与分子药理研究室,重庆400006 [3]海南省药品检验所海南省药物质量研究重点实验室,海南海口570216

出　　处：《中国药物应用与监测》2016年第4期206-210,共5页Chinese Journal of Drug Application and Monitoring

基　　金：国家自然科学基金面上项目(81173066)

摘　　要：目的:观察葛根素衍生物(G20)对局灶性脑缺血再灌注损伤大鼠是否具有保护作用,并探讨其作用机制,其保护作用是否与caspase-3的表达具有相关性。方法:以Longa发明的线栓法制作局灶性脑缺血再灌注模型,大鼠被随机分为6组,分别为假手术组、模型组、G(25.0 mg·kg^(-1))组、G20(12.5、25.0、50.0 mg·kg^(-1))组,给药组于缺血后1.5 h及6 h两次尾静脉给药。通过评价大鼠缺血后神经行为学、脑梗死面积及脑含水量的变化,HE染色观察脑组织神经元病理学改变,以观察G20是否具有脑缺血再灌注损伤保护作用;并以原位末端标记法检测大脑神经元凋亡数目的改变及免疫组化法检测其caspase-3的表达来探讨其作用机制。结果:G20能改善脑缺血后4 h、24 h的神经肌肉运动和前庭运动功能,减少脑缺血再灌注后脑梗死面积及降低脑含水量,减轻脑组织的病理形态学改变,与G组比较,未见大鼠尿液变红等不良反应。G20明显减少了脑组织凋亡细胞的数目,减少了caspase-3的表达。结论:G20对大鼠脑缺血再灌注损伤有保护作用,其机制可能是通过抑制caspase-3的表达发挥抗神经元凋亡作用。Objective： To observe the protection effect of puerarin derivative（G20） on focal cerebral ischemia and reperfusion injury in rats, and explore whether its mechanism is associated with the expression of caspase-3. Methods： Model of focal cerebral ischemia and reperfusion was induced using an intraluminal monofilament blockade by Longa. The rats were randomly divided into six groups, which were the sham-operation group, the model group, G group（puerarin 25.0 mg·kg^-1）, G20 groups（12.5, 25.0, 50.0 mg·kg^-1）. The rats in drug groups were administrated drugs in 1.5 h and 6 h after ischemia by tail vein. The neurological deficits were evaluated with neuroethology, the infarction size and brain edema after ischemia, respectively. The pathology of cerebral tissue was evaluated after ischemia by HE dyeing for observing the protective effect of G20. Neuronal apoptosis by TUNEL and the expression of caspase-3 by SABC were used for researching the mechanism. Results： G20 obviously improved movement of neuromuscular and vestibular function in 4 h and 24 h after ischemia, and obviously reduced the infarction size and brain edema, improved pathological morphology of rat brain after cerebral ischemia and reperfusion. Compared with G group, no adverse reaction such as red urine was found in G20 group. G20 decreased neuronal apoptosis and down-regulated the expression of caspase-3 of rats brain after cerebral ischemia and reperfusion. Conclusion： G20 had the protective effect on brain tissue damaged by focal ischemia and reperfusion in rats. The mechanism of G20 may be related to the inhibition of apoptosis by down-regulating the expression of caspase-3.

关 键 词：葛根素 葛根素衍生物 局灶性脑缺血再灌注 凋亡 CASPASE-3 

分 类 号：R285.5[医药卫生—中药学]