羟丁酸钠对新生大鼠缺血缺氧性脑损害的干预作用

The influence of sodium hydroxybutyrate on the hypoxic-ischemic brain damage in neonatal rats

目的 观察羟丁酸钠对新生大鼠缺血缺氧性脑损害的干预作用。方法 新生7dSD大鼠随机分为假手术组(S组)、生理盐水对照组(C组)、羟丁酸钠组(γ组),7组又分为γ_1、γ_2、γ_3组。各组20只。采用Rice法制作新生大鼠缺血缺氧性脑损害模型。C组缺血缺氧后即刻腹腔注射生理盐水,每日3次;γ_1、γ_2、γ_3组分别注射羟丁酸钠50、100和200 mg/kg,用法同C组。观察大鼠缺血缺氧后28d内存活率、脑部形态学改变、左/右大脑半球重量比值、左大脑半球含水量和学习记忆能力(Y-迷宫法)。结果 (1)C组动物存活率(60％)明显低于其余各组(P<0.05)。(2)学习记忆能力测试表明:C组达标率(41.7％)明显低于其他各组(P<0.05);γ_1组与γ_2、γ_3和S组相比,学习记忆能力较差;(3)C组和γ_1组左/右大脑半球湿重之比值明显小于γ_2、γ_3和S组(P<0.01或P<0.05);各组左侧大脑半球含水量差异无显著性(P<0.05);C组左侧大脑半球液化坏死后空洞发生率明显高于其他各组(P<0.05)。结论 羟丁酸钠对新生大鼠具有抗缺血缺氧性脑损害的作用。

Objective Hypoxic-ischemic brain damage (HIBD) is a life-threatening neonatal disease during perinatal stage. Since excitatory amino acids (EAAs) and their receptors are involved in the pathogenesis. Sodium hydroxybutyrate ( r-OH ), an intermediate metabolite of GABA, may have beneficial effects on HIBD. Methods One-hundred seven-day (7d) SD rat pups were randomly assigned to one of three groups:(Ⅰ) control group (n= 20);(Ⅱ) sham operation group (n=20)and (Ⅲ) r-OH group which was further divided into 3 subgroups according to the dose of r-OH 50 mg·kg-1 (r-OH1) (n=20),100 mg·kg-1 (r-OH2) (n=20),200mg·kg-1 (r-OH3) ( n=20).Animals in control group and r-OH group were subjected to left carotid artery ligation followed by 2 h of hypoxia (O2 :N2=8%:92%).Normal saline ( NS) was administered ip immediately after sham operation or hypoxia,then 3 times a day for 7 days in group Ⅰ and Ⅱ.In r-OH group r-OH was administered ip instead of NS. Brain damage was evaluated by survival rate, pathology, the ratio of weight of left to right hemisphere on the 28 th day after ischemia-hypoxia and the capacity of learning and memory using Y-Maze test. Results (1) The survival rate on the 28 th day after hypoxia or sham operation was significant lower in control group (60%) than that in the other groups (85%-95% ) (P<0.05).(2) The rate of learning capacity and memory up to the desired criteria was 41.7% in the control group, significantly lower than that in the other groups (80%-100% ) ( P <0.05).(3) The ratio of weight of left to right hemisphere on the 28th day after hypoxia or sham operation was significantly lower in control group and r-OH1 subgroup than that in the other groups (P<0.05 or 0.01).(4) The percentage of cavity formation in the left hemisphere was significantly higher in control group than that in the other groups (P<0.05).(5) There was no significant difference in water content of left hemisphere among the three groups. Conclusion Sodium hydroxybutyrate can protect brain from hypoxic-ischemic injury in rats.