摘要
目的:观察不同频率电针对脑缺血再灌注恢复期大鼠血脑屏障(BBB)开放效应,探讨电针促血脑屏障开放调控机制。方法:频率研究:150只健康雄性SD大鼠建立大脑中动脉闭塞(MCAO)模型,饲养3周后,按随机原则分为模型组、假手术组及2、15、30、50、100Hz组。检测大鼠脑含水量以及伊文思蓝(EB)透过量。机制研究:180只SD大鼠建立MCAO模型,饲养3周后,随机分为模型组、假手术组、电针组、假电针组、电针+PKC抑制剂组;检测大鼠大脑皮层蛋白激酶C亚型β1(PKCβ1)的磷酸化水平、P-糖蛋白(P-gp)以及mdr1a、mdr1b m RNA的表达。结果:2Hz组、100Hz组大鼠脑组织EB含量明显升高(P<0.05);模型组与其余4组比较,大鼠脑组织含水量差异无统计学意义。与模型组比较,2Hz组大鼠大脑皮层的PKCβ1、p-PKCβ1/PKCβ1均显著提高(P<0.05),电针组P-gp的IHS评分显著降低(P<0.05),电针组mdr1、mdr1b m RNA的表达均明显降低(P<0.05);电针+PKC抑制剂组mdr1a m RNA表达高于电针组(P<0.05)。结论:2Hz、100Hz电针刺激对脑缺血再灌注恢复期大鼠BBB均具有一定开放效应,且无明显脑水肿出现;电针诱导大鼠BBB开放可能是通过促使PKCβ1磷酸化,下调药物外排系统P-gp、mdr1a m RNA,抑制P-gp在大脑皮层毛细血管内皮细胞的表达实现。
Objective： To observe the opening effect of electro-acupuncture（EA） on blood-brain barrier（BBB） of recovered MCAO rats under different frequencies, and to discuss the opening regulation mechanism of BBB mediated by EA. Methods： Frequency research： One hundred and fifty healthy male SD rats were established MCAO model. The recovered rats were randomly divided into model group, EA 2 Hz, 15 Hz, 30 Hz, 50 Hz, 100 Hz and sham operation group after 3 weeks of feeding. The rats brain water content and penetration amount of Evans blue were measured. Mechanism research： One hundred and eighty healthy male SD rats were established MCAO model. The recovered rats were randomly divided into model group, sham operation group, EA group, pseudo-EA group, EA＋PKC inhibitor group after 3 weeks. The phosphorylation level of PKCβ1, m RNA expressions of P-gp, mdr1 a and mdr1 b were detected in the cerebral cortex. Results： The penetration amount of Evans blue in EA 2 Hz and 100 Hz groups were apparently higher than other groups（P〈0.05）. There was no significant difference on brain water content between the model group and the other 4 groups. Total PKCβ1 and the ratio of P-PKCβ1 and total PKCβ1 in the rat cerebral cortex increased significantly in the EA 2 Hz group（P〈0.05）, and the IHS score in the P-gp immunized group was significantly decreased（P〈0.05）. The m RNA expressions of mdr1 a and mdr1 b in EA group were significantly decreased（P〈0.05）. The m RNA expression of mdr1 a in EA＋PKC inhibitor group was higher than that in EA group（P〈0.05）. Conclusion： Both 2 Hz and 100 Hz EA stimulation have a certain open effect on BBB in cerebral ischemia reperfusion contusion rats, and there is no obvious brain edema. EA-induced BBB opening may be achieved by promoting the phosphorylation of PKCβ1, down-regulating m RNA expression of mdr1 a of P-gp, and inhibiting the expression of P-gp in the cerebral capillary endothelial cells.
作者
张江松
周慧
陈媛媛
张异
宋瑶
焦俊玥
林咸明
ZHANG Jiang-song;ZHOU Hui;CHEN Yuan-yuan;ZHANG Yi;SONG Yao;JIAO Jun-yue;LIN Xian-ming(Laboratory of Acupuncture Neurobiology, The Third Clinical Medical College of Zhejiang Chinese Medical University Hangzhou 310053, China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2018年第5期2097-2102,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81373758
No.81774407)
浙江省重点科技创新团队(No.2013TD15)~~
