生地大黄汤通过干预紧密连接蛋白Claudin-5、Occludin、Zo-1对自发性高血压大鼠脑出血模型脑水肿的改善作用

Improving Function of Shengdi Dahuang Decoction on the cerebral edema in spontaneously hypertensive rats with intracerebral hemorrhage by intervening with tight junction proteins Claudin-5,Occludin and Zo-1

目的:观察生地大黄汤对自发性高血压大鼠脑出血模型脑水肿的影响。方法:27只大鼠按随机数字表法分为假手术组、模型组和生地大黄汤组各9只,假手术组只开颅、钻孔、进针,另2组按自体血注入法建立脑出血大鼠模型。生地大黄汤组灌胃生地大黄汤(18.5g/kg/d),假手术组和模型组灌胃等体积纯水,每天1次,连续干预3 d,比较各组大鼠神经功能缺损评分、血肿周围脑水肿变化及紧密连接蛋白Claudin-5、Occludin、Zo-1表达情况。结果:造模后3 d,生地大黄汤组神经功能缺损评分低于模型组,脑水肿体积、脑含水量亦均低于模型组;脑出血2组血肿周围组织Claudin-5、Occludin、Zo-1表达水平较假手术组降低,但生地大黄汤组明显高于模型组,差异有统计学意义。结论:生地大黄汤对自发性高血压大鼠脑出血模型脑水肿有改善作用,能减少脑水肿体积,降低脑组织含水量,缓解神经功能缺损,其可能的机制与生地大黄汤干预紧密连接蛋白Claudin-5、Occludin、Zo-1相关。

Objective: To observe the effects of Rehmannia and Rhubarb Decoction( RRD) on brain edema in spontaneously hypertensive rats of intracerebral hemorrhage( ICH). Methods: 27 rats were randomly divided into sham group,ICH group and RRD group with 9 rats in each group. Craniotomy,drilling and needling were performed in sham group and the other two groups established models of intracerebral hemorrhage by autologous blood injection. The rats in RRD group were treated with RRD( 18. 5 g/kg/d) and those in other two groups were given the equivalent purified water.Once a day,the drug was continuously administered for 3 days. The neurological deficit scores,brain edema and expression of Claudin-5,Occludin,Zo-1 protein of tight junction around the hematoma were compared. Results: On postoperation 3 days,the neurological deficit scores in RRD group were significantly lower than those in ICH group,and edema volume and brain water content were also significantly lower. The expression of Claudin-5,Occludin,Zo-1 around the hematoma in both ICH group and RRD group were lower than that in sham group,but RRD group was higher than ICH group and the difference was statistically significant. Conclusion: Rehmannia and Rhubarb Decoction can ameliorate brain edema in spontaneous hypertensive rats of intracerebral hemorrhage by decreasing the volume of brain edema,reducing brain water content and improving neurological deficit. The possible mechanism is involved in RRD intervening Claudin-5,Occludin,Zo-1 protein of tight junction.