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目的探讨缺氧缺血性脑损伤(hypoxic ischemic brain damage,HIBD)大鼠应用醒脑静注射液治疗后血清S100B蛋白、低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达水平变化及意义。方法 7日龄Wistar大鼠96只,随机分为假手术组、HIBD组、醒脑静预处理组和醒脑静治疗组各24只。假手术组仅分离左颈总动脉不结扎,不作低氧处理;余3组分离左侧颈总动脉并结扎,制作HIBD大鼠模型。醒脑静预处理组于制备模型前腹腔注射醒脑静注射液10mL/kg,连续3d;醒脑静治疗组制备模型即刻腹腔注射醒脑静注射液10mL/kg,1次/d,连续注射至处死日;HIBD对照组制备模型即刻腹腔注射等量生理盐水。各组分别于模型制备后1、3、5、7d断头处死大鼠各6只,取脑组织RNA,采用实时荧光定量PCR法检测各组脑组织S100B,HIF-1α和VEGF mRNA表达水平。结果模型制备后1、3、5、7d,醒脑静预处理组S100BmRNA(1.4±0.2、2.6±0.4、3.0±0.3、1.6±0.2)、醒脑静治疗组S100B(1.3±0.1、2.1±0.2、1.7±0.2、1.4±0.3)明显低于HIBD组(1.7±0.2、2.8±0.3、3.6±0.5、2.2±0.5)(P<0.05),醒脑静预处理组HIF-1αmRNA(1.6±0.1、2.2±0.2、3.3±0.2、4.5±0.1)和VEGF mRNA(1.3±0.1、2.4±0.2、3.3±0.2、4.6±0.1)与醒脑静治疗组HIF-1αmRNA(1.7±0.2、4.1±0.1、5.6±0.1、7.3±0.2)和VEGF mRNA(1.6±0.1、3.1±0.2、5.2±0.2、6.4±0.3)均高于HIBD组[HIF-1αmRNA(1.5±0.2、1.8±0.1、2.2±0.2、2.8±0.2),VEGF mRNA(1.2±0.1、1.7±0.1、2.5±0.2、3.1±0.2)](P<0.05);以上数据均高于假手术组(P<0.05)。结论醒脑静注射液可上调HIBD大鼠HIF-1αmRNA和VEGF的mRNA表达,下调S100BmRNA表达。
Objective To investigate the effects of xingnaojing injection on serum levels of S100B protein, hypoxia inducible factor-1α (HIF-1α) and blood vessels in hypoxic ischemic brain damage (HIBD) rats. Vascular endothelial growth factor (VEGF) expression levels and significance. Methods Ninety-six Wistar rats aged 7 days were randomly divided into sham operation group, HIBD group, Xingnaojing preconditioning group and Xingnaojing treatment group. The sham-operated group was only isolated from the left common carotid artery without ligation and without hypoxia. The other three groups were separated from the left common carotid artery and ligated to make a HIBD rat model. Xingnaojing preconditioning group was given intraperitoneal injection of Xingnaojing injection 10mL / kg for 3 days before the model was prepared. Xingnaojing injection group was injected intraperitoneally with Xingnaojing injection 10mL / kg, once per day for continuous injection On the day of death, HIBD control group was injected intraperitoneally with equal volume of normal saline. Six rats in each group were sacrificed at 1, 3, 5 and 7 days after model preparation, RNA of brain tissue was taken and the expression of S100B, HIF-1α and VEGF mRNA in each group were detected by real-time fluorescence quantitative PCR. Results After S100B mRNA (1.4 ± 0.2, 2.6 ± 0.4, 3.0 ± 0.3, and 1.6 ± 0.2) in Xingnaojing preconditioning group and S100B (1.3 ± 0.1,2.1 ± 0.2, 1.7 ± 0.2, 1.4 ± 0.3) were significantly lower than those in HIBD group (1.7 ± 0.2,2.8 ± 0.3,3.6 ± 0.5,2.2 ± 0.5) (P <0.05) 0.1, 2.2 ± 0.2, 3.3 ± 0.2, 4.5 ± 0.1) and VEGF mRNA (1.3 ± 0.1, 2.4 ± 0.2, 3.3 ± 0.2, 4.6 ± 0.1) 0.1, 5.6 ± 0.1, 7.3 ± 0.2) and VEGF mRNA (1.6 ± 0.1,3.1 ± 0.2,5.2 ± 0.2,6.4 ± 0.3) were higher than those in HIBD group [HIF-1αmRNA (1.5 ± 0.2,1.8 ± 0.1,2.2 ± 0.2,2.8 ± 0.2), VEGF mRNA (1.2 ± 0.1,1.7 ± 0.1,2.5 ± 0.2,3.1 ± 0.2)] (P <0.05). The above data were all higher than those in sham operation group (P <0.05). Conclusion Xingnaojing Injection can up-regulate the mRNA and protein expression of HIF-1αmRNA and VEGF in HIBD rats and down-regulate the expression of S100B mRNA.