七叶皂苷钠对脑出血大鼠脑水肿的影响及其机制探讨

Effect of sodium aescinate on brain edema in rats with cerebral hemorrhage and the mechanism

目的观察七叶皂苷钠对脑出血大鼠脑水肿的影响,并探讨其可能的机制。方法将150只SD大鼠随机分为A、B、C组各40只和D组30只,A、B、C组参照Rosenberg等的方法进行苍白球定位注射制作脑出血模型;D组仅向颅内同部位针刺,留针相同时间,不注射药物。造模成功后,A、B、C组立即向腹腔分别注射溶解于1 mL生理盐水的七叶皂苷钠5、10 mg/(kg·d)及等量生理盐水,各组于脑出血后6 h及1、3、5、7 d断头取脑,收集脑组织标本。利用干湿重法测定脑组织含水量,免疫组化法检测血肿周围脑组织中的水通道蛋白4(AQP4)。结果 A、B、C组出血侧脑组织含水量及血肿周围AQP4表达在6 h内即开始明显升高,3 d达高峰,随后逐渐下降,7 d时仍高于D组(P<0.05或0.01);A、B组各时点脑组织含水量均明显低于C组(P均<0.01),B组均亦明显低于相应时间点的A组(P均<0.05)。各组大鼠不同时间点出血侧大脑含水量与血肿周围AQP4表达的灰度值呈正相关(r=0.862,P<0.01)。结论七叶皂苷钠可能通过抑制血肿周围AQP4表达减轻脑水肿,并具有一定的剂量依赖性。

Objective To observe the effect of sodium aescinate on brain edema in rats with cerebral hemorrhage and the mechanism of the drug. Methods A total of 150 SD rats were randomly divided into four groups, with 40 rats in group A, group B and group C respectively and 30 rats in group D. The models of cerebral hemorrhage in group A, B and C were made by globus pallidus positioning injection according to Rosenberg. Group D only received intracranial acupuncture for the same time as in other groups and without drug injection. After the models were successfully made, 5 or 10 mg/（ kg · d） of sodium aescinate dissolved in 1 mL of normal saline and the same volume of normal saline were immed.iately injected into the abdominal cavity in group A, B and C, respectively. The rats from each group were decapitated at 6 h and on the 1 st, 3rd, 5th and 7th day after cerebral hemorrhage and then the brain tissue specimens were collected. The water content in brain tissues was determined by wet-dry weighing method. Immunohistochemistry was used to detect the expression of aquaporin-4 （AQP4） in the brain tissues around hematoma. Results The water content in brain tissues of hemorrhage side and the expression of AQP4 around hematoma in group A, B and C began to increase within 6 h after cerebral hemorrhage, reached peak value on the 3rd day and then gradually declined, but were still higher than those of group D on the 7 th day （P 〈0.05 or 〈0.01 ）. Group A and B showed significant lower water content in brain tissues than that of group C at dif- ferent time points （ all P 〈0.01 ） and group B showed significant lower water content in brain tissues than that of group A at different time points （ all P 〈 0.05）. The water content in rat brain tissues in each group at different time points was posi- tively correlated with the grey value of AQP4 expression around the hematoma （r = 0.862, P 〈 0.01 ）. Conclusion Sodi- um aescinate can be used to inhibit the expressions of AQP4 around hematoma to alleviate cerebral edema and in a dose-dependent manner.