阿托伐他汀基于血液流变学改善与侧支循环血管建立对高原缺血性脑卒中大鼠的影响

Effects of atorvastatin on high altitude ischemic stroke in rats based on improvement of hemorheology and angiogenesis of collateral circulation

目的:构建高原缺血性脑卒中模型,探究阿托伐他汀对高原缺血性脑卒中大鼠的影响及其机制。方法:选择44只SD大鼠适应性喂养1周后,随机分为正常组(n=8)、假手术组(n=12)、脑缺血再灌注组(n=12)和阿托伐他汀组(n=12)。除正常组外,低氧环境中,各组大鼠高脂血症模型构建成功后开始脑缺血造模。连续给药阿托伐他汀(10 mg/kg)4周后进行神经功能评分,采血检测血脂水平及血液黏度。取脑进行2,3,5-三苯基氯化四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色,脑组织水肿程度检测,利用免疫组化检测神经血管新生,采用Western blot检测血管内皮生长因子(vascular endothelial growth factor,VEGF)与脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达水平。结果:与正常组相比,高原高血脂模型中各组大鼠血脂水平升高(P<0.05),血液黏度增加(P<0.05),阿托伐他汀连续4周给药能够有效降低血脂水平与血液黏度(P<0.05)。高原缺血性脑卒中大鼠中,与假手术组相比,中动脉栓塞模型没有影响大鼠血脂水平与血液黏度,但显著增加了大鼠脑梗死体积(P<0.05),提高了大脑含水量(P<0.05),最终导致神经功能损伤。阿托伐他汀则有效减少了大鼠脑梗死面积,降低了脑组织含水量并提高了大鼠神经功能评分。与此同时,阿托伐他汀给药有效提高了VEGF与BDNF表达水平,促进大鼠脑组织血管新生。结论:阿托伐他汀能够有效降低高血脂大鼠血脂水平,减少大鼠血液黏度,通过增加VEGF与BDNF表达水平,提高大鼠神经血管新生,减少脑梗死面积的同时改善高原缺血脑卒中大鼠神经功能。

Objective:To construct a model of high altitude ischemic stroke and explore the effect and mechanism of atorvastatin on high altitude ischemic stroke rats.Methods:After 1 week of adaption,SD rats were randomly divided into normal group,sham group,ischemia/reperfusion group and atorvastatin group.Except for the rats in normal group,the cerebral ischemia operation was constructed after the successful establishment of hyperlipidemia symptom in rats,after 4 weeks of continuous administration with atorvastatin(10 mg/kg),neurological scores were performed,and blood was collected from the submandibular vein for blood fat and blood viscosity detection.Then,the rats were anesthetized,the brains were taken for TTC staining,the whole brain was dried for brain edema detection,immunohistochemistry were used to detect angiogenesis,and Western blot was used to detect the expression levels of VEGF and BDNF.Results:Compared with normal group,the hypoxic and high-fat feed model resulted in the increase of blood fat(P<0.05)and blood viscosity(P<0.05)in each group.Administration of 4 consecutive weeks with atorvastatin could effectively reduce blood lipid levels and blood viscosity(P<0.05).In high altitude ischemic stroke,compared with sham group,the cerebral ischemia operation did not affect the blood fat and blood viscosity in rats,but significantly increased the cerebral infarct area(P<0.05)and increased the brain edema(P<0.05),which eventually lead to neurological damage.Atorvastatin could effectively reduce cerebral infarction area in rats,lowered the brain edema and improved the neurological score of rats.Meantime,the administration of atorvastatin effectively increased the expression levels of VEGF and BDNF and promoted angiogenesis in rat brain.Conclusion:.Atorvastatin can effectively reduce the blood fat and reduce the blood viscosity in hyperlipidemia rats.It can increase angiogenesis,reduce the cerebral infarction area and improve neurological function through increasing the expression of VEGF and BDNF in high altitude ischemic stroke.