黄芪干预缺血缺氧性脑损伤幼鼠脑组织一氧化氮及丙二醛含量的变化

背景幼鼠脑缺氧缺血后,脑组织水肿加重,脑组织中一氧化氮及丙二醛水平增高.黄芪具有增强免疫、耐缺氧以及改善心肌缺血再灌注损伤等药理作用.目的观察黄芪对缺血缺氧性脑损伤幼鼠脑组织一氧化氮及丙二醛含量的影响.设计随机对照实验.单位河北医科大学第二医院儿科,河北医科大学中医药研究院内科,河北医科大学病理生理教研室.材料实验于2004-02/04在河北医科大学病理生理学教研室完成.选取新生7 d龄SD大鼠40只,随机分为正常对照组、造模组、黄芪低剂量组、黄芪高剂量组,10只/组.黄芪注射液每10 mL相当于生药20g(由成都地奥九泓制药厂生产,批号0005028,河北医科大学中医药研究院医院提供).方法除正常对照组外,其余各组新生大鼠在清醒局麻状态下,行右侧颈总动脉结扎术建立缺氧缺血性脑损伤幼鼠模型.正常对照组给予生理盐水0.1 mL腹腔内注射;造模组每天腹腔注射质量浓度为9g/L的盐水0.1 mL;黄芪低剂量组与黄芪高剂量组每天分别腹腔注射黄芪注射液0.1,0.5 mL/次.各组于注射后即刻、第2,4天测头部血流量后断头取脑,进行脑组织含水量、一氧化氮及丙二醛含量的测定.主要观察指标[1]各组脑组织含水量.[2]各组头部血流量、一氧化氮及丙二醛含量测定结果.结果实验纳入40只大鼠全部进入结果分析.[1]各组脑组织含水量与正常对照组比较,造模组在造模即刻明显增加[(87.316±0.275),(88.259±0.297)%,P＜0.05],第2天仍未恢复正常水平[(86.973±0.265),(88.173±0.445)%,P＜0.05];与造模组比较,黄芪高剂量组第2天明显降低[(88.173±0.445),(86.542±0.141)%,P＜0.05].[2]各组头部血流量测定结果与正常对照组比较,造模组在造模即刻明显降低[(231.88±13.33),(139.54±10.58)mV,P＜0.05],至第4天仍未恢复正常水平[(234.57±14.38),(145.38±13.33)mV,P＜0.05];与造模组第4天比较,黄芪低、高剂量组均明显增加[(145.38±13.33),(288.45±12.89),(313.82±21.74)mV,P＜0.01].[3]各组头部一氧化氮及丙二醛含量测定结果造模组在造模即刻均明显高于正常对照组[(26.55±5.23),(19.67±7.17)μmol/L,P＜0.05;(7.88±2.55),(4.22±0.12)μmol/L,P＜0.01],第4天均显著高于正常对照组[(48.65±17.06),(18.65±2.12)μmol/L,P＜0.01;(5.29±0.68),(4.06±0.39)μmol/L,P＜0.05];与造模组比较,黄芪低、高剂量组第4天均明显降低[(48.65±17.06),(23.77±12.79),(24.67±11.54)μmol/L,P＜0.01;(5.29±0.68),(4.51±2.30),(3.68±0.39)μmol/L,P＜0.01].结论黄芪可明显消除缺氧缺血性幼鼠脑组织水肿,增加其脑组织血流量.通过降低一氧化氮及减少自由基损伤代谢产物丙二醛的含量,从而发挥抑制脂质过氧化损伤的作用.

Influences of Radix Astagali seu Hedysari on contents of nitric oxide and malondialdehyde in brain tissue of young rats with cerebral injury after cerebral ischemia and anoxia

BACKGROUND:After cerebral tissue ischemia and anoxia in young rats,the cerebral edema gets serious, and the levels of nitric oxide (NO) and malondialdehyde (MDA) decrease. Radix Astagali seu Hedysari has the pharmacological effects of enhancing immunity, anti-anoxia and improving myocardial ischemic reinfusion injury.OBJECTIVE: To investigate the influences of Radix Astagali seu Hedysari (huangqi) on contents of NO and MDA in brain tissue of young rats with cerebral injury after cerebral ischemia and anoxia.DESIGN:A randomized and controlled trial.SETTING: Department of Pediatrics, Second Hospital, Hebei Medical University; Department of Internal Medicine, Institute of Traditional Chinese Medicine, Hebei Medical University; Department of Pathophysiology, Hebei Medical UniversityMATERIALS:The experiment was conducted from January to April 2004at Department of Pathophysiology, Hebei Medical University. Total 40 SD rats, 7-day old, were at random divided as normal control group, model group, humgqi low-dose group and huangqi high-dose group, with 10 rats in each group. Huangqi injection (The content in 10 mL injection is consistent with 20 g raw drug) was provided by Institute of Traditional Chinese Medicine of Hebei Medical University (produced in Chengdu Di'ou Jiuhong Pharmaceutical Factory, Batch No. 0005028).METHODS:Except rats in normal group, those in the rest groups, under conscious and local anesthesia, were all given common carotid artery ligation, establishing cerebral injury model due to ischemia and anoxia. Rats in normal group were intraperitoneally injected 0.1 mL normal saline; rats in model group were intraperitoneally injected 9 g/L normal saline, 0.1 mL each day; rats in huangqi low-dose group and huangqi high-dose group were respectively given 0.1mL, 0.5 mL huangqi injection, once a day, intraperitoneally. Cerebral blood flow was detected immediately, 2 and 4days after injection. Then the rats were decapitated for collecting the brains to measure the water content in brain, the contents of NO and MDA.MAIN OUTCOME MEASURES: [1] Water contents in brains of rats in every group. [2] Cerebral blood flow, and the contents of NO and MDA.RESULTS:Totally 40 rats were involved in the trial and all entered in the final result analysis. [1] The water content in brain of each group: Compared with normal group, the content in model group was increased immediately after model establishment [(87.316±0.275)%, (88.259±0.297)% ,P ＜ 0.05 ],and did not return to the normal level at the second day [(86.973±0.265)%,(88.173±0.445)%,P ＜ 0.05]; compared with model group, the content in huangqi high-dose group was obviously decreased at second day[(88.173±0.445)%, (86.542±0.141)% ,P ＜ 0.05]. [2] Measurement of cerebral blood flow: compared with control group, the blood flow in model group was obviously decreased immediately after model establishment[(231.88±13.33), (139.54±10.58)mV,P＜ 0.05], and did not return to normal level till the 4th day [(234.57±14.38), (145.38±13.33)mV,P ＜ 0.05];compared with model group, the blood flow in huangqi low-dose group and huangqi high-dose group, at day 4, was obviously increased [(145.38±13.33),(288.45±12.89), (313.82±21.74)mV,P ＜ 0.01]. [3] The contents of NO and MDA: The contents in model group, immediately after model establishment, were obviously higher than those in normal control group [(26.55±5.23 ), ( 19.67±7.17 )μmol/L,P ＜ 0.05; (7.88±2.55), (4.22±0.12) μmol/L, P＜ 0.01], and at day 4, were significantly higher than those in normal control group [(48.65±17.06), (18.65±2.12)μmol/L,P ＜ 0.01; (5.29±0.68),(4.06±0.39)μmol/L,P ＜ 0.05]; compared with model group, the contents in huangqi low-dose group and huangqi high-dose group were obviously decreased at day 4 [(48.65±17.06), (23.77±12.79), (24.67±11.54)μ mol/L,P＜ 0.01; (5.29±0.68), (4.51±2.30), (3.68±0.39)μmol/L,P ＜ 0.01].CONCLUSION:Huangqi could obviously reduce cerebral edema from ischemia and anoxia, increase cerebral blood flow. It could decrease the contents of NO and MDA that is metabolite of free radical injury, thus playing its role to inhibit lipid peroxidation injury.