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

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

目的探讨6％羟乙基淀粉130／0．4（6％HES130／0．4）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300～350g，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％HES130／0．4组（HES组）．和晶体一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60min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％HES130／0．4；HHS组经股静脉输注等于放血量的HHS（10％HES130／0．4与7．5％NaCI按1：1混合），各复苏组均在30min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-10013蛋白浓度；于复苏180min时取脑组织，计算脑组织含水量，采用ELISA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-100G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-1008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％HES130／0．4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。

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） ; groupⅡ THI-HS; group Ⅲ normal saline （group NS） ; group Ⅳ 6% HES 130/0.4 and groupV HHS （1：1 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 mm Hg which was maintained for 1h. In group Ⅲ NS 3 times the volume of blood withdrawn was infused. In group IV 6 % HES 130/0.4 equal to the volume of blood withdrawn was infused.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 （T0,baseline）, 60 min after THI-HS （T1） and at 30, 60 and 180 min after fluid resuscitation （T2.4 ） 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-Ⅴ as 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-10013 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-α 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.