抗血小板溶栓素对局灶性脑缺血/再灌注大鼠脑损伤的作用观察

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (3): 274-278.

抗血小板溶栓素对局灶性脑缺血/再灌注大鼠脑损伤的作用观察

罗胜勇¹, 叶寿山¹, 李睿¹, 贾德云¹, 李心伟¹, 马征¹, 陈志武², 李小羿³, 张国辉³, 戴向荣³

¹安徽省医学科学研究院,合肥 230061,安徽;
²安徽医科大学药理学教研室,合肥 230032,安徽;
³兆科药业(合肥)有限公司,合肥 230088,安徽

收稿日期:2014-04-15 修回日期:2014-11-10 发布日期:2015-04-08
作者简介:罗胜勇,男,博士,副研究员,研究方向:心脑血管药理。Tel: 13855137256 E-mail: lsy770728@126.com
基金资助:
安徽省自然科学基金资助项目(1208085QH140)

Effect of anti-platelet thrombolysin on focal cerebral ischemia/reperfusion injury in rats

LUO Sheng-yong¹, YE Shou-shan¹, LI Rui¹, JIA De-yun¹, LI Xing-wei¹, MA Zheng¹, CHEN Zhi-wu², LI Xiao-yi³, ZHANG Guo-hui³, DAI Xiang-rong³

¹Anhui Provincial Institute of Medical Scince,Hefei 230061,Anhui,China;
²Dept of Pharmacology ,Anhui Medical University,Hefei 230032,Anhui China;
³Zhaoke Pharmaceutical(Hefei)Company Limited,Hefei 230088,Anhui,China

Received:2014-04-15 Revised:2014-11-10 Published:2015-04-08

摘要/Abstract

摘要： 目的: 观察抗血小板溶栓素(anti-platelet thrombolysin,APT)对缺血性脑损伤的保护作用并初步探讨其作用机制。方法: SD大鼠,随机分为假手术组(Sham)、模型组(缺血再灌注组)、阳性组(依达拉奉注射液)、APT高、中、低组。双侧颈动脉结扎,建立脑缺血模型,测定大鼠脑含水量,HE染色观察脑组织病理改变;线栓法建立大鼠脑缺血/再灌注模型,进行行为学评分,酶联免疫法(ELISA)及免疫组化测定脑组织中Toll样受体4(TLR4)、c-Jun氨基末端激酶(JNK)、Bax蛋白含量。结果: 与模型组比较,APT高、中剂量组可明显改善缺血再灌注后大鼠神经功能障碍症状,降低脑水肿程度,改善缺血后脑组织的病理改变,明显降低缺血后脑组织中TLR4、JNK、Bax蛋白表达。结论: APT对缺血性脑损伤有较好的保护作用,其机制可能与抑制脑组织中TLR4/JNK/Bax信号通路表达,从而抑制细胞凋亡有关。

关键词: 抗血小板溶栓素, 神经功能评分, TLR4, JNK, Bax

Abstract: AIM: To observe the protective function of anti-platelet thrombolysin(APT) on cerebral focal ischemia reperfusion injury in rats and its possible mechanisms.METHODS: SD rats were randomly divided into six groups:sham group,model group,positive control group,APT 0.02,0.01,0.005 mg/kg group. The chronic cerebral ischemia models were made by permanent bilateral occlusion of common carotid anteries. The water contents were measured by dry/wet weight method. The pathology changes of cerebral tissue were observed using light microscope .The focal ischemia-reperfusion injury model was induced by ligation of middle cerebral artery occlusion(MCAO), neurobehavioral score was evaluated in each group, the expressions of TLR4,JNK,Bax were detected by ELISA and immunohistochemistry.RESULTS: Compared with the model Group, the symptoms of neurological deficits were obviously relieved in APT(0.02,0.01 mg/kg)group;the water contents in brain tissue were decreased;the pathological changes were improved and the protein expressions of TLR4,JNK,Bax were reduced.CONCLUSION: APT has protective effect on focal cerebral ischemia/reperfusion injury in rats,which maybe related to the inhibition of apoptosis through restraining the expression of TLR4/JNK/Bax signal pathway.

Key words: anti-platelet thrombolysin, neurological score, TLR4, JNK, Bax

中图分类号:

R965.2

罗胜勇, 叶寿山, 李睿, 贾德云, 李心伟, 马征, 陈志武, 李小羿, 张国辉, 戴向荣. 抗血小板溶栓素对局灶性脑缺血/再灌注大鼠脑损伤的作用观察[J]. 中国临床药理学与治疗学, 2015, 20(3): 274-278.

LUO Sheng-yong, YE Shou-shan, LI Rui, JIA De-yun, LI Xing-wei, MA Zheng, CHEN Zhi-wu, LI Xiao-yi, ZHANG Guo-hui, DAI Xiang-rong. Effect of anti-platelet thrombolysin on focal cerebral ischemia/reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(3): 274-278.

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