黄芪多糖对缺血脑损伤大鼠海马神经递质及c-fos mRNA表达的影响

Effects of astragalan on neurotransmitters and expression of c-fos mRNA in hippocampus after ischemic brain injury in rats

目的:观察黄芪多糖(astragalan,AG)对缺血性脑损伤大鼠海马乙酰胆碱(ACh)、去甲肾上腺素(NE)、5-羟色胺(5-HT)及c-fos mRNA表达的影响。方法:取Wistar雄性大鼠100只,随机分成假手术组(sham-operated group,SOG)、模型组(model group,MG)、低剂量黄芪多糖治疗组(low-dose astragalan treatmentgroup,L-AGTG)、高剂量黄芪多糖治疗组(high-dose astragalan treatment group,H-AGTG),每组10只。所有MG和AGTG组颈部切开阻断右侧大脑中动脉,造成缺血性脑损伤后,AGTG组腹腔注射AG(5 mg.kg-1和15 mg.kg-1)。于1 d、3 d和7 d分别脑血流再灌注,随即评分神经功能缺损情况后取材,测定海马匀浆中ACh、NE和5-HT的含量,采用RT-PCR法半定量分析大鼠海马c-fos的mRNA水平。结果:AG能减轻脑缺血引起的海马损伤。L-AGTG 7 d和H-AGTG 3 d、7 d海马匀浆ACh、5-HT和NE的含量均显著高于MG而低于SOG(P<0.05或P<0.01),且呈现剂量递增趋势;SOG的c-fos mRNA表达低于MG(P<0.05或P<0.01),提示脑缺血因素造成了c-fos基因表达增强,加速了下游基因表达,有利于神经细胞的保护;H-AGTG 3 d、7 d c-fos mRNA表达均高于MG(P<0.05),提示黄芪多糖具有上调c-fos mRNA表达的作用。结论:黄芪多糖能减轻脑缺血再灌注引起的神经细胞损伤、改善海马神经功能,其作用机制与提高海马ACh、NE、5-HT含量和促进c-fos基因表达有关。

AIM： To explore the effects of astragalan（AG） on the neurotransmitters,acetylcholine（ACh）,norepinephrine（NE） and 5-hydroxytryptamine（5-HT）,and the expression of c-fos mRNA in hippocampus after ischemic brain injury in rats.METHODS： Male Wistar rats（180~220 g） were randomly divided into 10 groups（n=10）： sham-operated group（SOG）,3 model groups（MG 1 d,3 d,7 d） and 3 low-or high-dose AG treatment groups（L/H-AGTG 1 d,3 d,7 d）,respectively.The middle cerebral artery of the rats in MG group and AGTG group were blocked by operation to induced brain injury.The cerebral blood vessels of the animals were blocked on day 1,day 2 and day 7,respectively,after the L/H-AGTG were treated with AG（5 mg/kg and 15 mg/kg,ip）.The content of ACh,5-HT and NE was determined using their respective ELISA kits,and the expression of c-fos mRNA in the hippocampus homogenate was semiquantitative analyzed by RT-PCR after neurologic impairment（NIP） was scored.RESULTS： AG attenuated the injury in hippocampus by cerebral ischemia in a dose-dependent manner.The content of ACh,5-HT and NE in L-AGTG 7 d,H-AGTG 3 d and 7 d groups was significantly higher than that in MG group,but was lower in SOG group（P0.05 or P0.01）.The mRNA expression of c-fos in SOG group was lower than that in MG group（P0.05 or P0.01）,indicating that reinforcement expression of c-fos mRNA by cerebral ischemia and the expression of downstream genes may be beneficial for protecting the neurons.The mRNA expression of c-fos in H-AGTG 3 d/7 d groups was higher than that in MG group（P0.05）.CONCLUSION： AG attenuates the damage of neurons and improves the functions of hippocampus under the condition of cerebral ischemia/reperfusion by increasing the content of ACh,NA and 5-HT,and the mRNA expression of c-fos in hippocampus.