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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 Naoluoxintong Formula on angiogenesis and regional cerebral blood flow (r CBF) in rats with cerebral ischemia-reperfusion (MCAO / R) and its possible mechanism. Methods Totally 160 Wistar rats were randomly divided into normal group, normal control group, normal control group, normal control group, normal control group, low dose induction group, middle dose induction group and high dose induction group. Each dose was normal Rats in the induction group and the induction group were given intragastric administration of 400 mg / kg, 800 mg / kg and 1000 mg / kg of Naoxintongtong compound solution 1 g / (100 g · d) respectively. After 7 days of continuous gavage, The rats were injected intraperitoneally with 50% CCl4-olive oil solution, and the liver function of rats in each group was detected 24h after induction, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and albumin (Alb) were screened to screen safe dose. 90 rats were randomly divided into sham operation group, model group and Naoluo Xintong group, 30 rats in each group. MCAO / R model, according to the safe dose of experimental results given intragastric Xintong safe dose of liquid, respectively, on the 3rd, 7th, 14th days after intragastric administration of rat brain tissue thrombopoietin (TPO) Endothelin (ET) levels and vascular endothelial growth factor (VEGF) expression, and dynamic observation of r CBF. Results Compared with normal group, low dose normal group and middle dose normal group, ALT and AST increased, LDH and Alb in high dose normal group and each induced group decreased (P <0.05 or P <0.01) Compared with the dose-induced group, ALT and AST increased and Alb decreased (P <0.01) in the high and low dose groups, so the middle dose of 800mg / kg was safe dose. The levels of TPO and ET in the model group were significantly higher than those in the sham operation group (P <0.01). The levels of TPO and ET in the model group were significantly lower than those in the model group Increased, r CBF significantly recovered (P <0.05 or P <0.01). Compared with the third day, the levels of VEGF protein increased on the 7th and the 14th day, and increased on the 14th day of r CBF compared with the third day Increase (P <0.05 or P <0.01). Conclusion Naoluoxintong compound can improve the blood flow state, regulate local cerebral blood flow and salvage the ischemic penumbra neurons by regulating the coagulation and fibrinolytic regulatory factors, VEGF and angiogenesis in rats, Therapeutic effect of cerebrovascular disease.