摘要
目的:通过放射免疫法测定脑缺血模型大鼠脑组织中神经肽Y及白细胞介素2、白细胞介素6的含量,分析以去痰活络为治则的健脑制剂健脑宁改善其记忆障碍的可能途径。方法:实验于2000-07/2003-02在北京中医药大学东直门医院临床药理实验室完成。选取清洁级4月龄SD大鼠152只,取150只随机分为多发性脑梗死、中动脉脑梗死、去脑膜毛细血管造模大鼠各50只,每组模型随机再分为5组,即对照组、模型组、健脑宁11.25,3.75,1.25g/(kg·d)剂量组,每组10只,雌雄各半;余2只用于取血,配制血栓水溶液。健脑宁胶囊(由天麻、人参叶、枳壳等组成,武汉健民药业集团股份有限公司,批号:000205),实验时将药物用5g/L消毒羧甲基纤维素钠配制成混悬液。150只大鼠在无菌条件下采用由颈总动脉向颈内动脉注入同种动物血栓、结扎颈外动脉由颈外动脉向颈内动脉插线再灌注、开颅去皮质毛细血管的方法制造了3种实验性记忆功能减退实验动物模型,对照组均为假手术。术后对照组、模型组喂饲5g/L消毒羧甲基纤维素钠,健脑宁11.25,3.75,1.25g/(kg·d)剂量组,给生药剂量分别为11.25,3.75,1.25g/(kg·d),用5g/L消毒羧甲基纤维素钠配制,给药体积均为10mL/kg体质量。连续给药4周,麻醉取血,分离血浆,用放射免疫法测定中动脉脑梗死、多发性脑梗死、去皮质毛细血管模型大鼠脑组织中神经肽Y及白细胞介素2、白细胞介素6的含量。结果:每个模型组均取模型组9只,健脑宁11.25g/(kg·d)剂量组8只,3.75g/(kg·d)剂量组9只,1.25g/(kg·d)剂量组8只,对照组9只;剔除手术过程中死亡或造模不成功大鼠21只,最终129只进入结果分析。①实验4周后,多发性脑梗死、去脑膜毛细血管、中动脉脑梗死正常组大鼠海马组织中白细胞介素2含量明显高于模型组,白细胞介素6含量和血浆、海马、脑皮质、下丘脑组织中神经肽Y含量均明显低于模型组(P<0.05～0.01)。②多发性脑梗死、去脑膜毛细血管、中动脉脑梗死健脑宁11.25g/(kg·d)剂量组大鼠海马组织中白细胞介素2含量与模型组比较明显升高,白细胞介素6含量和血浆、海马、脑皮质、下丘脑组织中神经肽Y含量均明显降低(P<0.05～0.01)。③多发性脑梗死、去脑膜毛细血管健脑宁3.75g/(kg·d)剂量组大鼠海马组织中白细胞介素6、海马、脑皮质、下丘脑组织中神经肽Y含量与模型组比较明显降低,海马组织中白细胞介素2含量明显升高(P<0.05～0.01)。④去脑膜毛细血管健脑宁1.25g/(kg·d)剂量组大鼠海马组织中白细胞介素6、中动脉脑梗死大鼠血浆、下丘脑组织中神经肽Y含量与模型组比较均明显降低(P<0.05～0.01)。结论:健脑宁能调节3种脑缺血实验模型大鼠脑组织中白细胞介素2、白细胞介素6和神经肽Y的含量可能是其具有改善脑缺血模型大鼠记忆功能的重要机制。
AIM： To assay the contents of neuropeptide Y, interleukin-2 （IL-2） and interleukin-6 （IL-6） in brain tissue of model rats with cerebral ischemia with radio-immunity method so as to analyze the feasibility of jiannaoning on improving memory impairment according to removing the phlegm and activating collateral flow. METHODS： The experiment was completed at the Pharmacological Laboratdry of Dongzhimeng Hospital Affiliated to Beijing University of Traditional Chinese Medicine from July 2000 to February 2003. Totally 152 SD rats, aged 4 months, of clean grade, were selected in this study. Of 150 rats were randomly divided into multiple cerebral infarotion group, cerebral infarotion in medium-sized artery group and clearing blood capillary in meninges group with 50 in each group. Rats of half gender in each group were also divided into 5 subgroups： control group, model group, jiannaoning 11.25, 3.75 and 1.25 g/（kg·d） groups with 10 in each group. Other 2 rats were used to collect their blood to dispense aqueous solution of thrombus. jiannaoning capsule （consisted of tall gastrodia tuber, ginseng leaf and bitter orange, etc.; provided by Wuhan Jianmin Pharmaceutical Group Limited Company, batch number： 000205） was dispensed suspension with 5 g/L sterilizated carboxymethylcellulose sodium. Totally 150 rats were injected with the same kind of thrombus from common carotid artery to internal carotid artery; external carotid artery was ligated; drugs were perfused from external carotid artery to internal carotid artery; cranium was open; and cortex was devascularizated. Three kinds of experimental model rats of memory disorder were developed. Rats in control group were treated with sham operation. After operation, rats in control and model groups were given with 5 g/L sterilizated carboxymethylcellulose sodium according to 10 mL/kg body mass. Four weeks after medication, blood was selected and plasma was separated. The contents of neuropeptide Y, IL-2 and IL-6 in brain tissue of models rats in multiple cerebral infarction group, cerebral infarction in medium-sized artery group and clearing blood capillary in meninges group were measured respectively with radio-immunity method.
RESULTS： There were 9 rats in model group, 8 injiannooning 11.25 g/（kg·d） group, 9 injiannctoning 3.75 g/（kg·d） group, 8 injiannctoning 1.25 g/（kg·d） group and 9 in control group. Totally 21 rats were excluded because of death or failing model, and 129 entered the final analysis. ①Four weeks after experiment, content of IL-2 in hippocampus of rats in multiple cerebral infarction group, cerebral infarction in medium-sized artery group and clearing blood capillary in meninges group was significantly higher than that in model group, but content of IL-6 and contents of neuropeptide Y in plasma, hippocampus, cerebral cortex and hypothalami of rats were significantly lower than those in model group （P 〈 0.05-0.01）.② Content of IL-2 in hippocampus of rats in multiple cerebral infarction group, cerebral infarction in medium-sized artery group and jiannaoning 11.25 g/（kg·d） clearing blood capillary in meninges group was significantly higher than that in model group, but content of IL-6 and contents of neuropeptide Y in plasma, hippocampus, cerebral cortex and hypothalami of rats were significantly lower than those in model group （P 〈 0.05-0.01）. ③ Content of IL- 6 and contents of neuropeptide Y in plasma, hippocampus, cerebral cortex and hypothalami of rats in multiple cerebral infarction group, cerebral infarction in medium-sized artery group and jiannaoning 3.75 g/（kg·d） clearing blood capillary in meninges group were significantly lower than those in model group, but content of IL-2 in hippocampus was significantly higher than that in model group （P 〈 0.05-0.01）. ④ Content of IL-6 in jiannnoning 1.25 g/（kg·d） cleating blood capillary in meninges group, content of plasma in cerebral infarction in medium-sized artery group and content of neuropeptide Y in hypothalami of rats were significantly lower than those in model group （P 〈 0.05-0.01）.
CONCLUSION： Jiannaoning can regulate the contents of IL-2, IL-6 and NPY in brain tissue of three experimental model rats, which may be the important mechanism of its improving memory function of experimental model rats with cerebral ischemia.
出处
《中国临床康复》
CSCD
北大核心
2006年第11期32-35,共4页
Chinese Journal of Clinical Rehabilitation
