二异丙酚对脑出血大鼠脑组织NF-κB表达及超微结构的影响

The effect of propofol on the expression of nuclear factor-kappa B and the ultrastructure after intracerebral hemorrhage in rats

目的探讨二异丙酚对大鼠脑出血后NF-κB表达及超微结构的影响。方法将65只雄性SD大鼠随机分为正常对照组(5只)、假手术组(25只)、模型组(25只)和治疗组(10只),假手术和模型组根据动物处死时间又分为6、12 h组及1、2、4 d共5个亚组,治疗组分1、2 d共2个亚组。模型组与治疗组均采用Ⅶ型胶原酶定向注入诱导脑出血模型,假手术组以等量等渗盐水代替Ⅶ型胶原酶定向注入;治疗组给予二异丙酚100 mg/kg腹腔注射,1次/d,假手术组和模型组以等渗盐水代替二异丙酚腹腔注射。用蛋白质印迹(Western blot)法检测血肿周围脑组织NF-κB表达的动态变化。透射电镜观察术后2 d血肿周围神经细胞超微结构的变化。结果血肿周围脑组织NF-κB表达于出血后12 h明显增加(P<0.05),1 d达高峰(P<0.01),2 d开始下降(P<0.01),4 d时仍有表达(P<0.05);电镜下观察到出血后2 d神经细胞损伤明显。治疗组1 d和2 d的NF-κB表达(灰度值)分别为61±19、24±6,明显低于模型组的92±16、65±13,P<0.05;神经细胞超微结构改变亦比模型组减轻。结论脑出血后血肿周围组织有炎症反应机制参与,二异丙酚可以有效减轻脑出血后的炎症反应,保护神经细胞结构,其机制可能与抑制NF-κB表达有关。

Objective To investigate the effect of propofol on expression of nuclear factor-kappa B （NF-KB） and the uhrastructure after intracerebral hemorrhage （ICH） in rats. Methods Sixty-rive male adult Sprague-Dawley rats were randomly divided into normal group （ n = 5 ）, sham-operation group （ n = 25）, model group （ n = 25 ） and treatment group （ n = 10 ）. The sham-operation and model groups were redivided into 5 subgroups （6, 12 h, 1,2, and 4 days） according to the time that the rats were sacririced; the treatment group were redivided into 2 subgroups （1 and 2 days）. The model and treatment groups used a model of ICH induced by collagenase Ⅶ injection by stereotatic technique, and the sham-operation group used isotonic saline solution instead; the rats in the treatment group were injected propofol 100 mg/kg IP once a day, and the rats in the sham-operation and model groups were injected isotonic saline solution instead. The dynamic changes of the expression of NF-κB in the cerebral tissues surrounding the hematoma were assayed by Western blot. The uhrastructural changes of neurocytes surrounding the hematoma 2 days after the operation were observed with a transmission electron microscope. Results The expression of NF-κB increased significantly at 12 hours after ICH （P 〈 0. 05 ）. It reached maximum at 1 day （P 〈0. 01 ）, and began to decrease at 2 days （P 〈0. 01 ）, and continued to express at 4 days （P 〈 0. 05 ）. The neuronal injury was obvious 2 days after ICH under transmission electron microscope. The expressions of NF-κB （grey scale values） at 1 and 2 days in the treatment group were 61 ± 19 and 24±6, respectively, and they were significantly lower than 92 ±16 and 65 ± 13 in the model group （P 〈 0. 05）. The ultrastructural changes in neurons were also less severe than those in the model group. Conclusions Inflammatory reaction was involved in brain tissues surrounding hematoma after ICH. Propofol may effectively reduce the inflammatory reaction after ICH and protect the neuronal structures. Its mechanism may be associated with the inhibition of the expression of NF-κB.