淫羊藿苷对大脑中动脉阻塞诱导的缺血性脑卒中模型大鼠的保护作用（英文）

Protective effect of icariin on middle cerebral artery occlusion- induced rat stroke model

目的观察淫羊藿苷(ICA)对大脑中动脉阻塞诱导的缺血性脑卒中模型大鼠的保护作用,并探索其可能的作用机制。方法雄性SD大鼠随机分为假手术组、模型组、ICA低、高剂量组及阳性药组(n=14)。ICA低、高剂量组每日两次灌胃ICA 10、30 mg·kg-1,阳性给药组每日灌胃尼莫地平10 mg·kg-1,连续给药1周,末次给药2 h后采用右侧永久大脑中动脉阻塞(p MCAO)建立缺血性脑卒中模型。制模后继续给药。造模后24 h按Bederson法进行神经功能评分,TTC染色法测量脑梗死体积;HE染色观察缺血区组织的病理学变化;Real time RT-PCR测定梗死周围区TNF-α、IL-1β、COX-2及i NOS的mRNA表达;Western Blot检测梗死周围区COX-2和i NOS蛋白表达。结果 ICA明显降低了模型大鼠的神经功能评分,减少脑梗死体积,减轻缺血区组织的病理学损伤。同时,ICA明显抑制了p MCAO诱导的TNF-α、IL-1β、COX-2及i NOS的mRNA表达以及COX-2和i NOS的蛋白表达。结论 ICA对大鼠永久性脑缺血损伤有保护作用,其机制至少与抑制p MCAO后的炎症反应有关。

Objective To investigate the effect of icafiin （ICA） on ischemic stroke induced by permanent mid- dle cerebral artery occlusion （pMCAO） in rats and explore the possible mechanisms. Methods Male Sprague Dawley rats were randomly divided into 5 groups ： sham, model, low - and high - dose of ICA - treated groups and positive group （n = 14）. Low- and high -dose ICA -treated groups were administered with ICA （10 and 30 mg· kg^-1 ） by gavage twice per day and the positive group was given nimodipine （ 10 mg· kg^-1 ）, while sham and model were treated with volume -matched distilled water. One week later,2 h after drug administra- tion, acute ischemic stroke was induced by fight permanent middle cerebral artery occlusion （pMCAO） in rats and then drug administration was continued. Twenty - four hours after model establishment, the neurological function was scored by the Bederson Test. Cerebral infarction volume was determined by 2,3,5 -triphenyhet- razolium chlorid （TYC） staining and the pathologic change in ischemic area was evaluated by H. E. staining. The mRNA expression of tumor necrosis factor alpha （ TNF - α） , interleukin - 1 beta （ IL - 1β）, cyclooxygen- ase - 2 （ COX - 2） and inducible nitric oxide synthase （iNOS） in peri - infarct region were detected by real time RT - PCR and the protein expression of COX - 2 and iNOS were also detected by Western Blot. Results ICA sig- nificantly caused a decrease in the change of neurological function and cerebral infarction volume, and attenuated the pathologic injury in pMCAO rats. Moreover, ICA prevented up - regulation of the mRNA expression of in- flammatory factors, including TNF -α, IL -β, COX - 2 and iNOS induced by pMCAO. The protein levels of COX -2 and iNOS were protective effect on acute dramatically decreased by pretreatment with ICA （30 mg/kg）. Conclusion ICA has the ischemie stroke in rats. The mechanisms are, at least partly, due to the inhibition of inflammatory responses following pMCAO.