基于肝功能安全剂量选择的脑络欣通复方对脑缺血再灌注模型大鼠血管新生及局部脑血流量的影响  

Effects of Naoluo Xintong Compound Formula(脑络欣通复方) on Angiogenesis and Local Cerebral Blood Flow in Rats Model with Cerebral Ischemia and Reperfusion based on Safe Dose Selection for Liver Function

作　　者：谭辉[1] 王键[1] 尹婷婷[1] 胡建鹏[1] 王京华[1] 何玲[1] 徐伟[1] 

机构地区：[1]安徽中医药大学新安医学教育部重点实验室,安徽省合肥市梅山路103号230038

出　　处：《中医杂志》2016年第14期1231-1236,共6页Journal of Traditional Chinese Medicine

基　　金："十二五"国家科技支撑计划(2012BAI26B00);国家中医药管理局全国中医学术流派传承工作室建设项目[国中医药人教函(2012)228号];安徽省教育厅2016年度高校自然科学研究项目(KJ2016A404)

摘　　要：目的探讨脑络欣通复方对脑缺血再灌注(MCAO/R)模型大鼠血管新生及局部脑血流量(r CBF)的影响及可能作用机制。方法 160只Wistar大鼠,70只随机分成正常组、低剂量正常组、中剂量正常组、高剂量正常组、低剂量诱发组、中剂量诱发组和高剂量诱发组各10只,各剂量正常组与诱发组大鼠分别给予400 mg/kg、800 mg/kg、1000 mg/kg的脑络欣通复方溶液1 ml/(100 g·d)灌胃,连续灌胃7天后各诱发组大鼠采用50%CCl4-橄榄油溶液腹腔注射,诱发完成24h后检测各组大鼠肝功能包括血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)和白蛋白(Alb)水平,以筛选安全剂量;90只随机分为假手术组、模型组和脑络欣通组各30只,模型组和脑络欣通组采用线栓法制作MCAO/R模型,根据安全剂量实验结果灌胃给予脑络欣通组安全剂量药液,分别于灌胃第3、7、14天检测各组大鼠脑组织匀浆血小板生成素(TPO)、内皮素(ET)水平以及血管内皮生长因子(VEGF)的表达,并动态观察r CBF。结果与正常组、低剂量正常组、中剂量正常组比较,高剂量正常组及各诱发组大鼠ALT、AST均升高,LDH、Alb均降低(P<0.05或P<0.01);与中剂量诱发组比较,高、低剂量诱发组ALT、AST升高,Alb降低(P<0.01),故以中剂量800mg/kg为安全剂量。与假手术组比较,模型组TPO和ET水平明显升高,VEGF蛋白表达增加,r CBF降低(P<0.01);与模型组比较,脑络欣通组TPO和ET水平显著降低,VEGF蛋白表达增加,r CBF明显恢复(P<0.05或P<0.01)。脑络欣通组不同时间点比较,TPO、ET第7、14天较第3天水平明显下降,VEGF蛋白表达第7、14天较第3天增加,r CBF第14天较第3天显著增加(P<0.05或P<0.01)。结论脑络欣通复方可通过调节模型大鼠凝血纤溶调节因子、VEGF以及促进血管新生而改善血流状态、提高局部脑血流量,挽救缺血半暗带神经元,进而发挥对缺血性脑血管病的治疗作用�Objective To investigate the effects of Naoluo Xintong Compound Formula（脑络欣通复方） on angiogenesis and local relative cerebral blood flow（rCBF） in rats with middle cerebral artery occlusion / reperfusion（ MCAO /R） and its possible mechanism. Methods One hundred and sixty Wistar rats in total were used in the study. Seventy Wistar rats were randomly divided into a normal group,a low dose normal group,a middle dose normal group,a high dose normal group,a low dose induced group,a middle dose induced group,and a high dose induced group,with 10 rats in each group. Rats in the different dose normal groups and induced groups were given400 mg / kg,800 mg / kg,or 1000 mg / kg of Naoluo Xintong Compound Formula solution 1 ml /（ 100 g·d） for gavage,respectively. The rats in each induced group were injected with 50% CCl4 olive oil solution after 7 days of continuous gavage. Twenty-four h after inducing completed,liver function of rats,including serum levels of alanine aminotransferase（ ALT）,aspartate amino transfer enzyme（ AST）,lactate dehydrogenase（ LDH）,and albumin（ ALB） were tested to select safe dose. Another 90 Wistar rats were randomly divided into a sham operation group,a model group and a Naoluo Xintong Compound Formula group,with 30 rats in each group. MCAO / R model was made with thread embolism method in model group and Naoluo Xintong group. According to the results from the above safe dose experiment,safety dose of Naoluo Xintong liquid were given for gavage. On the 3rd,7th,and 14 th day of gavage,levels of homogenates thrombopoietin（ TPO） and endothelial（ ET）,as well as expression of vascular endothelial growth factor（ VEGF） in brain were tested,and dynamic observation r CBF was observed in each group. Results Compared with that in the normal group,low dose normal group,and middle dose normal group,the AST and ALT both increased,Alb and LDH decreased in high dose normal group and each of induced groups（ P 〈 0. 05 or P 〈 0. 01）; Compared with that in t

关 键 词：脑缺血再灌注 脑络欣通复方 血小板生成素 内皮素 血管内皮生长因子 脑血流量 

分 类 号：R285.5[医药卫生—中药学]