促甲状腺激素释放激素类似物 YM14673对大鼠脑损伤性脑水肿的作用及机制

背景YM14673为促甲状腺激素释放激素( thyrotropin-releasing hormone,TRH)类似物 ,具有脑保护作用.目前的许多研究都在探讨其脑保护作用是否通过脑损伤后对脑水肿形成的抑制而实现的.目的观察 TRH类似物 YM14673对脑损伤后血脑屏障的影响. 设计随机对照的实验研究.地点和对象实验地点北京市神经外科研究所;研究对象为 Wistar 大鼠60只,随机分为假手术组、生理盐水组、给药Ⅰ组( 0.1 mg/kg)、给药Ⅱ组( 1 mg/kg),每组 15只动物. 干预制作大鼠急性脑损伤模型,创伤前从股静脉注入伊文氏蓝用于测定血脑屏障通透性的改变.假手术组开骨窗,不进行创伤打击.其他组行创伤打击.打击后腹腔注射生理盐水或YM14673溶液,伤后 24 h处死,测定脑水含量及脑组织和血浆中的伊文氏蓝含量.主要观察指标①各组大鼠左右半球脑水含量变化.②各组大鼠左右半球及血浆中伊文氏蓝含量变化.结果大鼠脑损伤后,脑组织脑水含量生理盐水组明显高于假手术组 [左侧半球生理盐水组为(79.57± 0.47)%,假手术组为 (78.29 ± 0.63)%, t=3.98,P< 0.01],遭受直接打击的左侧半球其脑水含量明显高于右半球(t=4.74, P< 0.01).给药物 YM14673干预后左右半球的脑水含量均显著下降 [左侧半球给药Ⅰ组(0.1 mg/kg)为( 78.95± 0.21)%,给药Ⅱ组( 1 mg/kg)为( 78.92± 0.31)% ].不同剂量治疗组之间脑水含量无明显差异(P >0.05).急性脑损伤后,脑组织中伊文氏蓝含量明显升高 ,YM14673对其含量没有影响.血浆伊文氏蓝含量差异均无显著性意义.结论 YM14673可减轻急性脑损伤引起的脑水肿,但对血脑屏障通透性的升高没有影响.

Effect and mechanism of YM14673,an analog of thyrotropin-releasing hormone,to cerebral edema induced by brain damage in rats

BACKGROUND:As an analog of thyrotropin-releasing hormone(TRH), YM14673 has protective effects on brain.Many researches aim to explore wether the protective effects on brain of YM14673 are realized by the inhibition of cerebral edema. OBJECTIVE:To observe the effects of analog of TRH-YM14673 on blood brain barrier after brain damage. DESIGN:Randomized case control study. SETTING and MATERIALS:Experimental site:Beijing Institute of Neurosurgery.Sixty Wistar rats were randomly divided into sham-operation group,saline group,administrative group I(0.1 mg/kg)and administrative group II(1 mg/kg)with each of 15 rats. INTERVENTIONS:Acute brain damage model of rats were made.Evans blue was injected into femoral vein to test the change of permeability of blood-brain barrier in advance.Rats of sham-operation group were opened bone window without any strike.Rats of other groups were taken strike.Saline or YM14673 solution was injected after strike. Rats were executed after 24 hours to assay the water content of brain and the Evans blue content in brain tissue and plasma.MAIN OUTCOME MEASURES:①Changes of water contents in both hemispheres in rats of each group; ②Changes of Evans blue content in both hemispheres and plasma of rats. RESULTS:After brain damage occurred,the water content in brain tissue of saline group was much higher than that of sham-operation group[Left hemisphere:saline group( 79.57± 0.47)%, sham- operation group(78.29 ± 0.63)%, t=3.98,P< 0.01)].The water content of left hemisphere which suffered direct strike was much higher than that of right hemisphere(t=4.74,P< 0.01).After intervened by YM14673,the water contents of both hemispheres were greatly decreased [left hemisphere: in administrative group I(0.1 mg/kg),it was( 78.95± 0.21)%, in administrative group II( 1 mg/kg) ,it was( 78.92± 0.31)% ].There was no difference on water content of brain tissue of different dose groups(P >0.05).The Evans blue content of brain remarkably increased after acute brain damage. YM14673 did not influence the contents.There was no difference on Evans blue content in plasma between groups. CONCLUSION:YM14673 can relieve the cerebral edema induced by acute brain damage.However,there is no effect on increasing the permeability of blood-brain barrier.