摘要
目的：观察异丙酚对家兔全脑缺血再灌流（I/R）损伤的保护作用,探讨其作用机制。方法：24只家兔随机分为A、B和C组,每组8只,C组缺血30min再灌流4h,缺血前静注异丙酚5mg·kg^-1,随后输注异丙酚20mg·（kg·h）^-1直至实验结束;B组为单纯I/R组,A组仅分离血管不阻断。分别在缺血前15min（I0）及再灌流30min（R1）、2h（R2）和4h（R3）取颈内静脉血,测定血浆ET-1、MDA和SOD的含量,实验结束取皮层HE染色,光镜观察,并测量神经原核截面积。结果：①C组ET-1随再灌流时间延长缓慢增加,在R3时仅增加2倍,但较B组相应值显著降低（P〈0.05）;而B组成倍增加,至R3时增加4.9倍（P〈0.01）;②MDA在C组R1-R3无明显变化,较B组相应时点降低（P〈0.05）,而B组R1-R3较I0及A组各时点升高（P〈0.01）。SOD在C组R1-R3较B组同期明显增加;③C组核截面积比B组显著增加（172.28μm2vs105.63μm2,P〈0.05）;④光镜下C组皮层轻度水肿、核固缩较少,而B组皮层水肿明显,大量神经元坏死。结论：异丙酚通过增强机体抗氧化能力,抑制ET-1的合成和释放,阻断氧自由基和ET-1之间的恶性循环,从而保护脑I/R损伤。
Objective:To determine if propofol can attenuate brain injury following complete cerebral ischemia and reperfusion and to investigate its mechanism.Methods:Twenty-four rabbits were divided randomly into group A without vessels occlusion and propofol administration; group B with cerebral ischemia induced by clipping of bilateral external,internal carotid arteries and vertebral arteries for 30 min and then with the reperfusion lasting 4 hours; group C with propofol (5 mg·kg-1) 10min before occlusion and followed 20 mg·kg-1·h-1 intravenously till the end of procedure.A catheter was inserted into internal jugular vein and positioned so that the tip was in the jugular bulb.Blood samples were obtained through the catheter.The plasma concentrations of endothelin-1(ET-1) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD) were measured 10min before occlusion(I0), 30 min(R1), 2 h(R2) and 4 h (R3) after reperfusion.Hematoxylin and eosin staining for the cerebral tissue was processed.The nerve nucleus cross section area was analyzed.Results:①The concentration of ET-1 was significantly lower in group C than that in group B during reperfusion(P<0.05), that of ET-1 increased slowly with the development of reperfusion in group B, whereas it heightened rapidly and doubled in C group;② MDA level in group C was significantly lower at R1~R3 than that in group B respectively, Meanwhile that in group B following reperfusion was markedly higher than that before ischemia and in group A.But the changes of SOD was contrary to those of MDA in groups B and C;③The nerve nucleus cross section area in group C increased significantly than that in group B (172.28 μm2 vs 105.63μm2,P<0.05);④Under light microscope, Mild cerebral cortex edema, less karyopyknosis and nerve nucleus pyknosis were observed in group C.However, cerebral cortex edema, nucleus pyknosis were evident with cell dissolution.Conclusions:Propofol protected the brain from ischemia and reperfusion injury, through the promotion of antioxidant potential, and the activity of SOD and suppression of the production and release of ET-1.
