Department of ICU, the Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
Chin Med J (Engl). 2009 Oct 5;122(19):2346-51.
Neuroprotective strategies following cardiopulmonary resuscitation (CPR) are an important focus in emergency and critical care medicine. Matrix metalloproteinases (MMPs), especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemia-reperfusion injury after CPR.
One hundred and twenty rats were randomly assigned to sham-operated (n = 40), resuscitation treatment (n = 40), and resuscitation control (n = 40) groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation. In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation (ROSC), defined as restoration of supraventricular rhythm and mean arterial pressure (MAP) > or = 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours (n = 8). Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy.
In the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group (P < 0.05). Tissue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group (P < 0.05), they were lower than in the resuscitation control group (P < 0.05).
Expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury.
心肺复苏（CPR）后神经保护策略是急救和重症监护医学的一个重要研究方向。基质金属蛋白酶（MMPs），尤其是 MMP9 因其在局灶性脑缺血/再灌注损伤中的作用而受到广泛关注。在大鼠局灶性脑缺血模型中，SB-3CT 可抑制 MMP9 的表达，减轻脑水肿，但尚无关于 CPR 后全脑缺血再灌注损伤的研究。
将 120 只大鼠随机分为假手术组（n=40）、复苏治疗组（n=40）和复苏对照组（n=40）。假手术组仅行麻醉和气管插管，复苏治疗组和复苏对照组大鼠均采用窒息法致心跳骤停。复苏治疗组大鼠在自主循环恢复（ROSC）后行腹腔内注射 SB-3CT，定义为恢复窦性节律和平均动脉压（MAP）>或=60mmHg 超过 5 分钟。复苏对照组大鼠也实施 ROSC，但不注射 SB-3CT。大鼠处死，立即取标本，然后在死亡后 3、9、24 和 48 小时（n=8）时取标本。测量脑组织 MMP9 蛋白、MMP9mRNA、水含量、伊文思蓝含量、TNF-α、IL-1 和 IL-6 的表达，并用电子显微镜观察脑组织超微结构。
复苏对照组大鼠脑组织 MMP9 蛋白和 mRNA、水含量、伊文思蓝含量、TNF-α、IL-1 和 IL-6 的表达在复苏后 3 小时明显升高，并在复苏后 24 小时达到高峰，与假手术组比较差异有统计学意义（P<0.05）。复苏对照组大鼠脑组织超微结构也发生改变。而复苏治疗组虽然与假手术组比较，各指标均升高（P<0.05），但均低于复苏对照组（P<0.05）。
CPR 后大鼠脑组织 MMP9 蛋白和 mRNA、水含量、伊文思蓝含量、TNF-α、IL-1 和 IL-6 的表达增加，表明血脑屏障破坏和过度炎症反应。用 SB-3CT 降低 MMP9 的表达，可减轻脑损伤。
