Wang Wei, Wang Jun, He Yan-Fang, Chen Qun-E, Zhu Hong-Mei, Zhou Chang-Mei, Zhang Shao-Mei
Department of Pediatrics, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Zhonghua Yi Xue Za Zhi. 2009 Apr 28;89(16):1144-7.
To investigate the effects of Shenmai injection containing active principles of Ginseng and ophiopogon root on the expression of hypoxia-inducible factor 1-alpha (HIF-1alpha) in brain after hypoxic-ischemic brain damage (HIBD).
108 neonatal SD rats were randomly divided into 2 equal groups: (1) Shenmai group (Group SM), undergoing ligation of the right common carotid artery to establish HIBD models, breathing immediately a mixed gas with 8% oxygen and 92% nitrogen for 2 hours to cause HI insult, and then injected intraperitoneally with Shenmai injection 10 mg/kg once a day for 7 days, and (2) normal saline (NS) group (Group NS) undergoing ligation of the right common carotid artery to establish HIBD models, breathing immediately a mixed gas with 8% oxygen and 92% nitrogen for 2 h, and then injected intraperitoneally with NS 10 mg/kg once a day for 7 days. Another 54 neonatal rats underwent sham operation but did not undergo hypoxia as control group (Group C), 2, 12, and 24 hours, and 3, 7, and 14 days after HI insult 9 rats from each group were killed with their right hippocampal tissues taken out. Flow cytometry was used to examine the apoptotic rate of the hippocampal neurons. RT-PCR was used to detect the mRNA expression of HIF-1alpha.
(1) The apoptosis rate of the right hippocampal tissues began increase 2 h after Hi insult, peaked 24 h after HI, then gradually decreased, and almost returned to the original levels 14 d after HI. There was no significant differences in apoptosis rates 14d after HI among the 3 groups (all P > 0.05). The neuron apoptosis rates 12 h, 24 h, 3 d, and 7 d after HI of Group SM were all significantly lower than those of Group NS (e.g 24 h: (11.95 +/- 1.13)% vs (16.80 +/- 1.44)%, all P < 0.05). (2) The HIF-1alpha mRNA expression level in right brain began to increase 2 h after HI, peaked 24 h after HI, then gradually decreases, and returned to the original level 14 d after Hi in both Group SM and Group NS; The HIF-1alpha mRNA expression in right brain 12 h, 24 h, 3 d, and 7 d after HI of Group SM were all significantly higher than those of Group NS (e.g 24 h: (44.32 +/- 4.03)% vs (35.63 +/- 3.73)%, all P < 0.05).
The HIF-1alpha mRNA expression in brain tissue is up-regulated after HI insult. Shenmai injection helps increase the mRNA expression of HIF-1alpha in brain and reduces the apoptosis of hippocampus neurons after HI insult.
探讨含人参和麦冬有效成分的参麦注射液对缺氧缺血性脑损伤（HIBD）后大鼠脑组织缺氧诱导因子1α（HIF-1α）表达的影响。
将108只新生SD大鼠随机分为两组：（1）参麦组（SM组），结扎右侧颈总动脉建立HIBD模型，立即吸入含8%氧气和92%氮气的混合气体2小时造成HI损伤，然后腹腔注射参麦注射液10mg/kg，每日1次，共7天；（2）生理盐水（NS）组（NS组），结扎右侧颈总动脉建立HIBD模型，立即吸入含8%氧气和92%氮气的混合气体2小时，然后腹腔注射NS 10mg/kg，每日1次，共7天。另取54只新生大鼠行假手术但不进行缺氧处理作为对照组（C组）。HI损伤后2、12和24小时以及3、7和14天，每组处死9只大鼠，取出右侧海马组织。采用流式细胞术检测海马神经元凋亡率。采用RT-PCR检测HIF-1α的mRNA表达。
（1）右侧海马组织凋亡率在HI损伤后2小时开始升高，HI后24小时达到峰值，然后逐渐下降，HI后14天几乎恢复到原来水平。HI后14天3组凋亡率差异无统计学意义（均P>0.05）。SM组HI后12小时、24小时、3天和7天的神经元凋亡率均显著低于NS组（如24小时：（11.95±1.13）%对（16.80±1.44）%，均P<0.05）。（2）右侧脑组织中HIF-1α mRNA表达水平在HI后2小时开始升高，HI后24小时达到峰值然后逐渐下降，SM组和NS组HI后14天均恢复到原来水平；SM组HI后12小时、24小时、3天和7天右侧脑组织中HIF-1α mRNA表达均显著高于NS组（如24小时：（44.32±4.03）%对（35.63±3.73）%，均P<0.05）。
HI损伤后脑组织中HIF-1α mRNA表达上调。参麦注射液有助于增加HI损伤后大鼠脑组织中HIF-1α的mRNA表达，并减少海马神经元凋亡。
