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[参附注射液对新生大鼠缺氧缺血性脑损伤的影响:实验研究]

[Effects of Shenfu injection on hypoxic-ischemic brain damage: experiment with neonatal rats].

作者信息

Wang Jun, Yang Li-juan, Zhou Chang-mei, Zhu Hong-mei, Zhang Shao-mei

机构信息

Department of Neonatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2006 Nov 14;86(42):2994-7.

Abstract

OBJECTIVE

To investigate the effect of Shenfu (ginseng and aconite root) injection on hypoxic-ischemic brain damage (HIBD).

METHODS

Sixty 7-day-old Sprague-Dawley rats undergoing ligation of left common carotid artery and then put into a container with 8% O2 and 92% N(2) for 2 h so as to establish HIBD models, were randomly divided into 3 groups: Shenfu injection pretreatment group (since 4 days before the experiment Shenfu injection 10 ml/kg was injected intraperitoneally once a day for 4 days), Shenfu injection treatment group [Shenfu injection 10 ml/kg was injected intraperitoneally immediately after hypoxic-ischemia (HI) insult once a day for 7 days], and control group (normal saline 10 ml/mg was injected intraperitoneally immediately after HI insult once a day for 7 days). Twenty neonatal rats underwent sham operation as control group. The 4 groups were further divided into subgroups of 6 rats according to the time points: 2 hours before and 2 hours, 12 hours, 24 hours, 3 days, 7 days, 14 days, and 28 days after HI insult. 3, 7, 14, and 28 days after the HI insult the body weight was observed and the survival rate was observed 28 d after the HI insult. At different time points the rats of different subgroups were killed and their brains were taken out. Flow cytometry was used to calculate the neuron apoptosis rate in the hippocampal CA1 region.

RESULTS

The body weight increase levels 3, 7, 14 and 28 days after HI insult of the control group were all significantly less than those of the sham operation group (e.g 7 days: 8.8 g +/- 2.1 g vs 14.0 g +/- 2.9 g, all P < 0.01) and the body weight increase levels 3, 7, 14, and 28 days after HI insult of the control group were all significantly less than those of the Shenfu injection pretreatment group (e.g 7 d: 11.7 g +/- 3.3 g) and Shenfu injection treatment group (e.g 7 d: 10.9 g +/- 2.7 g, P < 0.01 or P < 0.05). The survival rate 28 d after HI insult of the control group was 60%, significantly less than those of other groups (all P < 0.05), and there was no significant difference in the survival rate among the other groups (all P > 0.05). Compared with the sham operation group the neuron apoptosis rates of the hippocampal CA1 region of the Shenfu injection treatment group and Shenfu injection pretreatment group began to increase 2 hours after HI insult, peaked 24 hours after, then gradually decreased, and recovered to normal 14 days after. The neuron apoptosis rates 2, 12, 24, 72 hours, and 7 days after HI insult of the Shenfu injection pretreatment group were all significantly lower than those of the control group (e.g 24 hours: 16.0% +/- 4.2% vs 11.9% +/- 2.3% vs 18.1%, P < 0.01 or P < 0.05), and the neuron apoptosis rates 72 hours and 7 days after HI insult of the Shenfu injection treatment group were significantly lower than those of the control group.

CONCLUSION

Shenfu injection can enhance the physical development and elevate the survival rate of neonatal rats with HI insult, and significantly prevents apoptosis of the hippocampus neurons from HI insult.

摘要

目的

探讨参附注射液对缺氧缺血性脑损伤(HIBD)的影响。

方法

将60只7日龄的Sprague-Dawley大鼠,结扎左侧颈总动脉后置于含8%氧气和92%氮气的容器中2小时,以建立HIBD模型,随机分为3组:参附注射液预处理组(从实验前4天开始,每天腹腔注射参附注射液10 ml/kg,共4天)、参附注射液治疗组[缺氧缺血(HI)损伤后立即腹腔注射参附注射液10 ml/kg,每天1次,共7天]和对照组(HI损伤后立即腹腔注射生理盐水10 ml/mg,每天1次,共7天)。20只新生大鼠行假手术作为对照组。4组再根据时间点分为每组6只大鼠的亚组:HI损伤前2小时、损伤后2小时、12小时、24小时、3天、7天、14天和28天。HI损伤后3、7、14和28天观察体重,并在HI损伤后28天观察存活率。在不同时间点处死不同亚组的大鼠,取出大脑。采用流式细胞术计算海马CA1区神经元凋亡率。

结果

HI损伤后3、7、14和28天对照组的体重增加水平均显著低于假手术组(如7天:8.8 g±2.1 g对14.0 g±2.9 g,均P<0.01),且HI损伤后3、7、14和28天对照组的体重增加水平均显著低于参附注射液预处理组(如7天:11.7 g±3.3 g)和参附注射液治疗组(如7天:10.9 g±2.7 g,P<0.01或P<0.05)。HI损伤后28天对照组的存活率为60%,显著低于其他组(均P<0.05),其他组间存活率无显著差异(均P>0.05)。与假手术组相比,参附注射液治疗组和参附注射液预处理组海马CA1区神经元凋亡率在HI损伤后2小时开始升高,24小时达到峰值,然后逐渐下降,并在14天后恢复正常。HI损伤后2、12、24、72小时和7天参附注射液预处理组的神经元凋亡率均显著低于对照组(如24小时:16.0%±4.2%对11.9%±2.3%对18.1%,P<0.01或P<0.05),HI损伤后72小时和7天参附注射液治疗组的神经元凋亡率显著低于对照组。

结论

参附注射液可促进HI损伤新生大鼠的体格发育,提高存活率,并显著预防HI损伤所致海马神经元凋亡。

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