基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.

Exploration of the effect of inhibitor of matrix metalloproteinase-9 on blood brain barrier in cardiopulmonary resuscitation in rats

Objective To explore the effect of inhibitor of matrix metalloproteinase-9 (MMP-9, SB-3CT) on blood brain barrier (BBB) after cardiopulmonary resuscitation (CPR) in rats. Methods Rats were randomly divided into three groups : the sham-operated group, the resuscitation control group, and the resuscitation treatment group. Cardiac arrest was produced by clamping the endotracheal intubation, and CPR was executed 1 minute later. In the resuscitation treatment group, SB-3CT (25 mg/kg) was injected intraperitoneally after the restoration of spontaneous circulation (ROSC). The rats we re executedimmediately, and 0, 3, 9, 24 and 48 hours after the treatment. BBB was examined, and the expression of MMP-9 protein and MMP-9 mRNA in brain tissue were detected, and the ultramierostructure of brain tissue was studied with electron microscopy. Results In the sham-operated group, the water content, Eyans blue content, MMP-9 protein, and MMP-9 mRNA did not change significantly, and there was no obvious change in microstructure of brain tissue. The expression of MMP-9 protein and MMP-9 mRNA in the resuscitation control group were obviously up-regulated at 3 hours after CPR, peaking at 24 hours. There was also significant change in BBB. The differences were significant statistically compared with sham-operated group. The changes in the resuscitation treatment group were similar to the resuscitation control group, but the levels were lower than those of the resuscitation control group (P<0. 05 or P<0. 01). Conclusion The specific inhibitor of MMP-9 (SB-3CT) could decreased the expression of MMP-9, the injury of BBB, and cerebral edema in the cerebral isehemia model with CPR rats, and the protection of cerebral ischemia/ reperfusion (I/R) injury after CPR is obvious.