摘要
目的建立缺血性中风气虚血瘀证病证结合大鼠模型,观察补阳还五汤及拆方对缺血性中风气虚血瘀证大鼠脑血流及脂质代谢的影响以探讨中药复方的作用机制。方法多因素复合模拟法制备气虚血瘀证模型后再采用线栓法制备缺血性中风大鼠模型。按随机数字表法将雄性SD大鼠分为正常组、模型组、补气拆方组(10.8 g/kg)、活血拆方组(2.2 g/kg)、补阳还五汤组(13.1 g/kg)、辛伐他汀组(10.0 mg/kg),各给药组灌胃相应的药物,正常组和模型组灌胃等量的蒸馏水,连续灌胃7 d后取材并检测指标。气虚证、血瘀证及神经功能评分法评价病证结合模型是否成功;激光散斑血流成像系统观察局部脑血流量(rGBF);全自动生化分析仪检测血胆固醇(CHO)、甘油三酯(TG)低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)的水平;蛋白质印迹法检测脑组织中腺苷酸活化蛋白激酶(AMPK)及其磷酸化腺苷酸活化蛋白激酶(p-AMPK)的表达。结果与正常组相比,模型组rGBF值、HDL-C水平降低(P<0.05),CHO、TG、LDL-C水平升高(P<0.01),AMPK、p-AMPK蛋白表达量降低(P<0.01)。给药7 d后,与模型组相比,补阳还五汤组及补气拆方组气虚证、血瘀证及神经功能评分均降低(P<0.05,P<0.01);各给药组rGBF值、AMPK及p-AMPK蛋白表达量均升高(P<0.01),血清TG水平均降低(P<0.01);补阳还五汤组及辛伐他汀组HDL-C水平升高(P<0.05),CHO、LDL-C水平降低(P<0.05,P<0.01);辛伐他汀组、补阳还五汤组及补气拆方组p-AMPK/AMPK比值升高(P<0.05)。结论补阳还五汤能通过改善脂质代谢状态,调整脑血流,从而发挥防治缺血性中风气虚血瘀证的作用,方中的补气药和活血药具有协同作用。
Objective To establish a rat model of ischemic stroke with the pattern of qi deficiency and blood stasis to observe the effects of Buyang Huanwu Tang(Yang-Supplementing and Five-Returning Decoction,BYHWT)and its disassembled prescription on cerebral blood flow and lipid metabolism in rats with ischemic stroke of qi deficiency and blood stasis pattern and explore the mechanism of compound prescriptions of traditional Chinese medicine.Methods The model of qi deficiency and blood stasis pattern was simulated by multiple factors.Then the rat model of ischemic stroke was prepared using the suture-occluded method.Male SD rats were randomly divided into normal group,model group,Buqi(supplementing qi,BQ)group(10.8 g/kg),Huoxue(circulating blood,HX)group(2.2 g/kg),BYHWT group(13.1 g/kg)and simvastatin(SV)group(10 mg/kg).Each treatment group was given the corresponding medication via gavage,and the normal and model groups were given the equal amounts of distilled water.After continuous intragastric administration for seven days,the samples were collected and the indexes were tested.Qi deficiency pattern,blood stasis pattern and neurological function score were used to evaluate the success of the combined model of disease and pattern.The cerebral blood flow was evaluated by a laser speckle flow imaging system.Blood cholesterol(CHO),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected by an automatic biochemical analyzer.The expression of adenosine monophosphate-activated protein kinase(AMPK)and phosphorylated adenosine monophosphate-activated protein kinase(p-AMPK)in brain tissue was observed by Western blotting.Results Compared with the normal group,the cerebral blood flow ratio and the HDL-C level were decreased(P<0.05);the CHO,TG and LDL-C levels were increased(P<0.01);the protein expression of AMPK and p-AMPK was decreased(P<0.01)in the model group.After seven days of the administration,compared with the model group,qi-deficiency pattern,blood stasis pattern and neurological function scores in the BYHWT group and BQ group were decreased(P<0.05).The cerebral blood flow ratio and the protein expression of AMPK and p-AMPK were increased(P<0.01)while the TG level decreased(P<0.01)in all treatment groups.The HDL-C level was increased(P<0.05)while the CHO and the LDL-C levels decreased(P<0.05 or P<0.01)in the BYHWT group and SV group.The p-AMPK/AMPK ratio was increased(P<0.05)in the BYHWT,BQ,and SV groups.Conclusion BYHWT may prevent and treat ischemic stroke with the pattern of qi deficiency and blood stasis by improving lipid metabolism and regulating cerebral blood flow.The qi supplementing and blood circulating medicinals in the formula seems to have synergistic effects.
作者
杨璐平
孙红梅
盖聪
程翠翠
王旭
马浩洁
张宇昕
张锦坤
YANG Luping;SUN Hongmei;GAI Cong;CHENG Cuicui;WANG Xu;MA Haojie;ZHANG Yuxin;ZHANG Jinkun(School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《北京中医药大学学报》
CAS
CSCD
北大核心
2022年第10期1029-1036,共8页
Journal of Beijing University of Traditional Chinese Medicine
基金
国家自然科学基金项目(No.81774110)
北京中医药大学新奥奖励基金项目(No.2019-XAJLJJ-YJ-005)
北京中医药大学校级自主课题项目(No.2020-JYB-XSCXCY-082)。
关键词
补阳还五汤
拆方
缺血性中风
气虚血瘀证
脑血流量
脂质代谢
大鼠
Buyang Huanwu Decoction
divided formula
ischemic stroke
qi deficiency and blood stasis pattern
cerebral blood flow
lipid metabolism
rats