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目的探讨不同次数和剂量异丙酚预处理对大鼠全脑缺血再灌注损伤的作用及其有关机制。方法176只雄性Wistar大鼠随机分为5组：假手术组(SH组,n=16)；缺血再灌注组(1组,n= 16)；异丙酚预处理1次组(P1组,n=48)；异丙酚预处理3次组(P3组,n=48)；异丙酚预处理5次组(P5组,n=48)。异丙酚预处理组又随机分为3个亚组：50 mg·kg~(-1)亚组、100 mg·kg~(-1)亚组、150 mg·kg~(-1)亚组(n=16)。P5组的各亚组在脑缺血前5d桉不同剂量腹腔注射异丙酚5d,容量不足5 ml者,用脂肪乳补足；P3组的各亚组注射脂肪乳2 d,异丙酚3 d；P1组的各亚组注射脂肪乳4d,异丙酚1d；SH组、Ⅰ组腹腔注射脂肪乳5 ml/d,共5 d。采用Pulsinelli-Brierley四血管闭塞法制备全脑缺血模型,全脑缺血20 min再灌注72h后,进行动物神经缺陷评分(NDS),随后断头取脑,观察海马CA1区神经元损伤程度的组织学分级(HG)、海马CA1区内未损伤的锥体细胞神经元密度(ND),原位末端标记法(TUNEL)检测凋亡细胞,计算凋亡指数(AI),原位杂交法测定海马脑源性神经营养因子(BDNF)mRNA及其受体酪氮酸激酶B(TrkB)mRNA的表达。结果1．除P1组的50 mg·kg~(-1)亚组外,其余各预处理组的ND、BDNF mRNA及TrkB mRNA表达均高于1组,NDS、HG和A1均低于Ⅰ组(P＜0．05)；2．与50 mg·kg~(-1)亚组相比,100mg·kg~(-1)、150mg·kg~(-1)亚组的ND、BDNF mRNA及TrkB mRNA表达均升高,NDS、HG和AI均降低(P＜0．05),100mg·kg~(-1)及150mg·kg~(-1)亚组间各指标差异无统计学意义(P＞0．05)；3．与PI组相比．P3组、P5组的ND、BDNF mRNA和TrkB mRNA表达均升高,NDS、HG和AI均降低(P＜0．05)．P3组、P5组间差异无统计学意义(P＞0．05)。结论异丙酚预处理可减轻大鼠全脑缺血再灌注损伤；在一定限度内,增加预处理次数和剂量可增强脑保护效果．其机制与BDNF和TrkB表达上调的程度有关。
Objective To investigate the effects and mechanisms of propofol preconditioning with different times and doses on global cerebral ischemia-reperfusion injury in rats. Methods 176 male Wistar rats were randomly divided into 5 groups: sham operation group (SH group, n = 16), ischemia reperfusion group (group 1, n = 16), propofol pretreatment group (P1 group , n = 48). Propofol was pretreated three times (group P3, n = 48) and propofol pretreated five times (group P5, n = 48). Propofol pretreatment group were randomly divided into three subgroups: 50 mg · kg -1 subgroup, 100 mg · kg -1 subgroup and 150 mg · kg -1 subgroup (n = 16). Each subgroup of P5 group was given intraperitoneal injection of propofol for 5 days with different doses of Eucalyptus 5 days before cerebral ischemia, ; The subgroups of group P1 were injected with fat emulsion for 4 days and propofol for 1 day; Group SH, group I was injected intraperitoneally with 5 ml / d of fat emulsion for 5 days. The model of global cerebral ischemia was established by Pulsinelli-Brierley four-vessel occlusion method. After global ischemia for 20 min and reperfusion for 72h, animals were subjected to neurological deficit score (NDS), then decapitated and the brain was taken to observe the neuronal damage in hippocampal CA1 area (HG), uninjured pyramidal neuron density (ND) in hippocampal CA1 region, apoptotic cells were detected by TUNEL, apoptosis index (AI) was calculated, and in situ hybridization Expression of hippocampal BDNF mRNA and its receptor tyrosine kinase B (TrkB) mRNA. Results 1. The levels of ND, BDNF mRNA and TrkB mRNA in all other pretreatment groups were higher than those in group 1 except for 50 mg · kg -1 subgroup in group P1, but NDS, HG and A1 were lower than those in group Ⅰ (P < 0.05); 2. Compared with 50 mg · kg -1 subgroup, the expressions of ND, BDNF mRNA and TrkB mRNA in 100 mg · kg -1, 150 mg · kg -1 subgroup were all increased, while NDS, HG (P <0.05). There was no significant difference between the two groups (P> 0.05) .3. Compared with PI group. The expressions of ND, BDNF mRNA and TrkB mRNA in P3 and P5 groups were increased, while NDS, HG and AI were decreased (P <0.05). There was no significant difference between P3 and P5 (P> 0.05). Conclusion Propofol preconditioning can attenuate global cerebral ischemia-reperfusion injury in rats. Within a certain limit, pretreatment and prophylaxis may increase the protective effect of cerebral protection. The mechanism is related to the up-regulation of BDNF and TrkB expression.