锦鸡儿总黄酮预处理对局灶性脑缺血再灌注损伤模型大鼠血脑屏障通透性的影响及机制研究
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篇名: 锦鸡儿总黄酮预处理对局灶性脑缺血再灌注损伤模型大鼠血脑屏障通透性的影响及机制研究
TITLE:
摘要: 目的:研究锦鸡儿总黄酮(TFC)预处理对局灶性脑缺血再灌注损伤模型大鼠血脑屏障通透性的影响及机制,为其进一步开发和临床用于治疗缺血性脑卒中提供参考。方法:将120只大鼠随机分为假手术组、模型组、尼莫地平组(阳性对照,12.6 mg/kg)和TFC高、中、低剂量组(60、30、15 mg/kg),每组20只。各给药组大鼠灌胃相应药物,假手术组和模型组大鼠灌胃等量生理盐水,每天1次,连续7 d。末次灌胃2h后,除假手术组外的其余各组大鼠均采用线栓法复制局灶性脑缺血再灌注损伤模型。再灌注24 h后,进行神经功能缺损评分,采用2,3,5-氯化三苯基四氮唑染色计算脑梗死面积百分比,分光光度法测定脑组织中伊文思蓝含量以考察血脑屏障的通透性;Western blot法检测脑缺血半暗带区基质金属蛋白酶9(MMP-9)、MMP-2和血脑屏障紧密连接相关蛋白Claudin-5、Occluding的表达。结果:与假手术组比较,模型组大鼠神经功能缺损评分、脑梗死面积百分比、脑组织中伊文思蓝含量和脑缺血半暗带区MMP-9、MMP-2蛋白表达水平均显著升高(P<0.01),脑缺血半暗带区Claudin-5、Occluding蛋白表达水平显著降低(P<0.01)。与模型组比较,除TFC低剂量组大鼠脑缺血半暗带区MMP-2蛋白表达水平降低不显著外,其余各组大鼠上述指标均显著改善(P<0.05或P<0.01)。结论:TFC对大鼠局灶性脑缺血再灌注损伤具有一定的预防作用,可改善神经功能缺损,减少脑梗死面积;其机制可能与抑制MMP-9、MMP-2蛋白表达,促进Claudin-5、Occluding蛋白表达,降低血脑屏障的通透性有关。
ABSTRACT: OBJECTIVE: To study the effects of the pretreatment of total flavonoids of Caragana sinica (TFC) on the permeability of blood-brain barrier in focal cerebral ischemia-reperfusion injury model rats, and to provide reference for further development and clinical treatment of cerebral ischemia stroke. METHODS: A total of 120 rats were randomly divided into sham operation group, model group, nimodipine group (positive control, 12.6 mg/kg) and TFC high-dose, medium-dose and low-dose groups (60, 30, 15 mg/kg), with 20 rats in each group. Administration groups were given relevant medicine intragastrically. Sham operation group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 7 d. 2 h after last intragastric administration, focal cerebral ischemia-reperfusion injury model was established by suture-occluded method in those groups except for sham operation group. 24 h after reperfusion, neurological deficit score was performed; 2,3,5-TTC staining was used to calculate the percent age of cerebral infraction area; the content of Evans blue was measured by spectrophotometer so as to investigate the permeability of blood-brain barrier. The expression of matrix metalloproteinases 9 (MMP-9), MMP-2 and blood-brain barrier closely linked protein (Claudin-5 and Occluding) in penumbra area of cerebral ischemic area were detected by Western blot. RESULTS: Compared with sham operation group, neurological deficit score, the percentage of cerebral infraction area, the content of Evans blue in cerebral tissue, the protein expressions of MMP-9 and MMP-2 in penumbra area of cerebral ischemic area were increased significantly (P<0.01); the protein expressions of Claudin-5 and Occluding in penumbra area of cerebral ischemic area were decreased significantly (P<0.01). Compared with model group, above indexes of rats in each medicine group were all improved significantly except that the decrease of protein expression of MMP-2 in penumbra area of cerebral ischemic area was not significant in TFC low-dose group (P<0.05 or P<0.01). CONCLUSIONS: TFC can prevent focal cerebral ischemia-reperfusion injury of rats, improve neurological deficit and reduce cerebral ischemia area and the permeability of blood-brain barrier. The mechanism of it may be associated with inhibiting the expressions of MMP-9 and MMP-2, promoting the protein expressions of Claudin-5 and Occluding.
期刊: 2018年第29卷第13期
作者: 张亚洲,何前松,胡斐然,樊梓媛
AUTHORS: ZHANG Yazhou,HE Qiansong,HU Feiran,FAN Ziyuan
关键字: 锦鸡儿总黄酮;局灶性脑缺血再灌注损伤;血脑屏障;血脑屏障紧密连接相关蛋白;预防作用;大鼠
KEYWORDS: Total flavonoids of Caragana sinica; Focal cerebral ischemia-reperfusion injury; Blood-brain barrier; Blood-brain barrier closely linked protein; Preventive effect; Rats
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