步长脑心通胶囊对血管性痴呆大鼠认知功能及脑组织血管紧张素Ⅱ、精氨酸加压素含量的影响

Effects of Buchang naoxintong on cognitive function and contents of angiotensin Ⅱ and arginine vasopressin in brain tissues of vascular dementia rats

目的:观察步长脑心通对血管性痴呆大鼠认知功能及脑组织血管紧张素Ⅱ、精氨酸加压素含量的影响,并与甲磺酸双氢麦角毒碱作用效果进行比较。方法:实验于2005-07/11在解放军第三军医大学大坪医院野战外科研究所七室完成。①选用清洁级15～18月龄Wistar大鼠48只,雌雄不拘,体质量(200±20)g。按随机摸球法将48只大鼠分为4组:假手术组、模型组、中药组和西药组(阳性对照组),每组12只。除假手术组外(进行假手术),其余组大鼠均采用改良Pulsinellis四血管阻断法建立血管性痴呆模型。中药组:以0.45g/(kg·d)剂量灌胃步长脑心通混悬液,由咸阳步长制药有限公司生产,由黄芪、乳香、没药、全蝎、地龙等16味中药组成,0.4g/粒;西药组:以0.32mg/(kg·d)剂量灌胃甲磺酸双氢麦角毒碱混悬液,该药由瑞士山德士药厂与天津华津制药厂合作生产,生产批号:970141,1mg/片;假手术组和模型组灌胃同容量生理盐水;每天分早、中、晚3次。术后当天开始用药,连续8周。②于造模前,造模后2,4,8周进行穿梭箱检查,以主动回避反应比率表示大鼠的认知能力。于给药结束后采用放射免疫分析法测定大鼠大脑皮质、下丘脑、海马血管紧张素Ⅱ、精氨酸加压素含量。③对数据进行单因素方差、均数间多重比较q检验;数据间相关性处理采用直线相关分析。结果:造模过程中如有动物死亡则补充相应只数,最终进入结果分析的大鼠保持为48只。①主动回避反应比率:模型组和中、西药组大鼠术后2,4,8周明显低于假手术组(P<0.01);2个治疗组均明显高于模型组(P<0.01);两治疗组间比较,差异不明显(P>0.05)。②血管紧张素Ⅱ含量:模型组大鼠大脑皮质、下丘脑和海马明显高于假手术组(P<0.01),中、西药组明显低于模型组(P<0.01),两治疗组间差异不明显(P>0.05)。③精氨酸加压素含量:模型组大鼠大脑皮质、下丘脑和海马明显低于假手术组(P<0.01);中、西药组明显高于模型组(P<0.01);中药组大脑皮质、下丘脑明显高于西药组(P<0.05),在海马与西药组相近(P>0.05)。④相关性分析结果:假手术组、模型组、中药组和西药组大鼠海马血管紧张素Ⅱ含量与主动回避反应比率呈负相关(r=-0.894,-0.872,-0.928,-0.880,P<0.05),而上述各组大鼠海马精氨酸加压素含量与主动回避反应比率呈显著正相关(r=0.912,0.892,0.937,0.897,P<0.05)。结论:步长脑心通改善血管性痴呆模型大鼠认知功能的作用可能是通过降低海马等脑组织血管紧张素Ⅱ含量、提高精氨酸加压素含量而实现,作用效果与甲磺酸双氢麦角毒碱相当。

AIM： To observe the effects of Buchang naoxintong （BCNXT） on cognitive function and content of angiotensin Ⅱ （Ang Ⅱ ） and arginine vasopressin （AVP） of distinct encephalic region in vascular dementia rats. and compare. the curative effect of BCNXT with hydergine （the main components of which were co-dergocrine mesylate）. METHODS： The experiment was carried out in the Seventh Room. Research Institute of Surgery. Duping Hospital. Third Military Medical University of Chinese PLA from July to November 2005. ① Forty-eight Wistar rats of clean class （15-18 months. 200±20 g. of either sex） were divided into sham operation group （n=12）. model group （n=12）. Chinese crude drag group （n=12） and western drug group （negative control group） （n=12） by random number table method. Except the rats in the sham operation group, the rest were used to establish the vascular dementia rat model by modified Pulsinellis 4-vessel occlusion. Rats in the Chinese crude drug group were treated with gastric perfusion of 0.45 g/kg BCNXT per day. The BCNXT produced by Xianyang Buchang Limited Company were composed of 16 Chinese herbs such as astragali, libanotus, gum myrrh, scorpion, ground dragon and so on, 0.4 g per grain. The rats in the western drug group were treated with gastric perfusion of 0.32 mg/kg hydergine per day suspl. The hydergine was produced by Switzerland Sandoz LTD and Tianjin Huajin Pharmaceutical Factory with the lot number 970141, 1 mg per tablet. Those in the sham operation group and model group received the same volume saline, in the morning, afternoon and evening every day, respectively. The drug was given at the day after operation for 8 weeks. ② At pre-operation and 2, 4, 8 weeks after 4-vessel occlusion, the cognitive function were observed by computerized shuttle-training case and expressed by the ratios of active avoidance response （AAR）. The contents of AngⅡ and AVP in cerebral cortex, hypothalamus and hippocampus were observed by radio immunoassay （RIA） technology after administration. ③The data was dealt with the single factor analysis of variance, and multiple comparisons among the means were done by the q-test. Dependability disposal among the data were done by linear correlation analysis. RESULTS： During the experiment, another was complemented if the rats died. Totally 48 rats were involved in analysis of results. ①Comparison of AAR ratio of rats in every group： At weeks 2, 4 and 8 after 4-vessel occlusion, the model, Chinese crude drug and western drug groups was significantly lower than the sham operation group （P 〈 0.01）. The two-treatment groups were markedly higher than the model group （P 〈 0.01）, and there were no significant difference between them （P 〉 0.05）. ②The content of Ang Ⅱ ： In cerebral cortex, hypothalamus and hippocampus, the content of Ang Ⅱ in the model group rats had significantly improvement as compared with the sham operation group （P 〈 0.01）. The Chinese crude drug and western drug groups had significantly drop as compared with the model group （P〈 0.01）, but no significant difference was found between them（P 〉 0.05）. ③The content of AVP： In cerebral cortex, hypothalamus and hippocampus, the content of AVP in the model group rats was obviously lower than the sham operation group （P 〈 0.01）, and the Chinese crude drug and western drug groups had significantly improvement as compared with the model group （P 〈 0.01）. In cerebral cortex and hypothalamus, content of AVP in the Chinese crude drug group was markedly higher than the western drug group （P 〈 0.05）, but in hippocampus, no significant difference was found between them. ④ Dependability correlation analysis： AAR ratio/Ang Ⅱ levels in the sham operation, model, Chinese crude drug and the western drug groups was negative correlation significantly （r=-0.894,-0.872, -0.928,-0.880, P 〈 0.05）, and AAR ratio/AVP levels in the sham operation, model, Chinese crude drug and the western drug groups was positive correlation significantly （r=0.912,0.892,0.937,0.897, P 〈 0.05 ）. CONCLUSION： BCNXT significantly improves cognitive function in vascular dementia rats, and its modification and control are possibly realized through reducing the content of Ang Ⅱ and increasing in the content of AVP in encephalic region such as hippoeampus, and so on, The effect of BCNXT is equivalent to co-dergocfine mesylate.