6%羟乙基淀粉130/0.4液体复苏对创伤性脑损伤合并失血性休克大鼠的脑保护作用

目的 探讨6%羟乙基淀粉130/0.4(6%HES 130/0.4)液体复苏对创伤性脑损伤合并失血性休克大鼠的脑保护作用.方法 健康成年雄性SD大鼠60只,体重300～350 g,随机分为5组(n=12):假手术组(S组)、模型组(M组)、生理盐水组(NS组)、6%.HES 130/0.4组(HES组)和晶体.胶体高渗透压混合液组(HHS组).分别参照Feeney改良法和Wiggers改良法制备大鼠创伤性脑损伤模型和失血性休克模型.S组仅切开头皮,钻开骨窗,不制备创伤性脑损伤和失血性休克模型;M组制备创伤性脑损伤和失血性休克模型;其余3组均制备创伤性脑损伤和失血性休克模型,并于休克60 min时开始复苏.NS组经股静脉输注3倍于放血量的生理盐水;HES组经股静脉输注等于放血量的6%HES 130/0.4;HHS组经股静脉输注等于放血量的HHS(10%HES 130/0.4与7.5%NaCl按1:1混合),各复苏组均在30 min内将液体输注完毕.实验期间记录平均动脉压(MAP),采用ELISA法测定血清S-100β蛋白浓度;于复苏180 min时取脑组织,计算脑组织含水量,采用EUSA法测定脑组织TNF-α和IL-6的含量.结果 与M组比较,NS组、HES组和HHS组复苏后MAP和脑组织含水量升高,HES组脑组织TNF-α和IL-6的含量降低,HES组和HHS组复苏后血清S-100蛋白浓度降低(P<0.05),NS组血清S-100β蛋白浓度差异无统计学意义(P>0.05);与NS组比较,HES组和HHS组复苏后MAP升高,脑组织含水量和血清S-100β蛋白浓度均降低,HES组脑组织TNF-α和IL-6的含量降低(P<0.05);与HES组比较,HHS组脑组织TNF-α和IL-6的含量升高,血清S-100β蛋白浓度升高(P<0.05),MAP差异无统计学意义(P>0.05).结论 6%HES 130/0.4液体复苏可对创伤性脑损伤合并失血性休克大鼠产生脑保护作用,且该作用强于HHS,其脑保护作用的机制可能与降低脑组织炎性反应有关.

Protective effect of fluid resuscitation with 6% hydroxyethyl starch 130/0.4 on the brain in a rat model of traumatic head injury complicated with hemorrhagic shock

Objective To investigate the protective effect of 6% hydroxyethyl starch (HES) 130/0.4 on the brain in a rat model of traumatic head injury (THI) complicated with hemorrhagic shock (HS) .Methods Sixty male SD rats weighing 300-350 g were randomized into 5 groups ( n - 12 each): group Ⅰ sham operation (group S);group Ⅱ THI-HS;group Ⅲ normal saline (group NS) ;group Ⅳ 6% HES 130/0.4 and group V HHS (1M mixture of 10% HES 130/0.4 + 7.5% NaCl) . The animals were anesthetized with intraperitoneal 10% chloral hydrate 4 ml/kg. Bilateral femoral arteries and right femoral vein were cannulated for MAP monitoring, blood letting and fluid resuscitation. In group Ⅱ-Ⅴ THI was produced according to the method described by Feeney. HS was induced by blood-letting (modified Wiggers Method) . MAP was reduced to 40 nun Hg which was maintained for 1 h. In group Ⅲ NS 3 times the volume of blood withdrawn was infused. In group Ⅳ 6% HES 130/0.4 equal to the volume of blood withdrawn was infused. Blood samples were taken before THI (T_0,baseline) , 60 min after THI-HS (T_1 ) and at 30, 60 and 180 min after fluid resuscitation (T_(2-4) ) for determination of serum S-100β protein concentration. Six animals in each group were killed at 3 h after resuscitation. Cerebral water and TNF-α and IL-6 contents were measured. Results MAP was restored to the baseline level immediately after resuscitation in group Ⅲ , Ⅳ and Ⅴ and was significantly higher in group Ⅳ(group HES) and Ⅴ (group HHS) than in group Ⅲ(group NS) . THI-HS significantly increased brain water content in group Ⅱ-Ⅴas compared with group I (group S) . Brain water content was significantly higher in the 3 resuscitation groups (group Ⅲ, Ⅳ, Ⅴ) than in group Ⅱ(THI-HS without resuscitation) . Resuscitation with NS induced higher brain water content than resuscitation with HES and HHS (group Ⅳ, Ⅴ). Serum S-100β concentration was increasing after THI-HS. The increase in serum S-100β concentration was attenuated by resuscitation with HES or HHS especially HES in group Ⅳ. The TNF-a and IL-6 contents in the brain tissue were significantly increased by THI-HS. Resuscitation with HES significantly attenuated the increase in TNF-α and IL-6 induced by THI-HS.Conclusion Resuscitation with 6% HES 130/0.4 can restore MAP and decrease brain edema induced by THI-HS by inhibition of inflammatory response.