自发性高血压大鼠永久性脑缺血模型建立的研究

The Study of the Establishment of a Permanent Brain Ischemic Model in Spontaneously Hypertensive Rat

目的在比较自发性高血压大鼠(SHR)与同龄无高血压Wistar大鼠永久性大脑中动脉阻塞(pMCAO)后脑缺血损伤情况并初步分析其可能机制。方法雄性SHR和Wistar大鼠各30只分别随机分为:pMCAO模型6 h组、假手术6 h组、pMCAO模型24 h组、假手术24 h组和正常组(均n=6)。采用线栓法制作pMCAO模型,术后6、24 h对大鼠进行神经功能学评分后处死,制作脑冠状切片。术后6 h处死大鼠脑部切片行尼氏染色后在组织学层面上观察神经元损伤情况;术后24 h处死大鼠脑部切片行尼氏染色后计算脑梗死体积和水肿程度百分比。正常组脑部切片经苏木精-伊红染色后计算脑部小血管壁/腔比。结果术后6和24 h,不同品系大鼠神经功能学评分差异无统计学意义(P>0.05);术后6 h尼氏染色示SHR神经元损伤重于Wistar大鼠。术后24 h SHR脑梗死体积百分比[(28.05±2.38)%]大于Wistar大鼠[(25.23±1.33)%],差异有统计学意义(P<0.05)。两品系大鼠之间脑水肿程度差异无显著性。脑部小血管壁/腔比SHR[(11.46±3.74)%]较Wistar大鼠[(8.73±1.73)%]增大(P<0.05)。结论 pMCAO术后SHR的脑缺血损伤程度重于Wistar大鼠,可能与高血压引起的脑侧支循环血管壁增厚、僵硬,自我调节能力降低有关。

Aim To compare the cerebral ischemic injury between spontaneously hypertensive rats （SHRs） and age-matched normotensive Wistar rats and preliminarily analyses the possible mechanisms. Methods Thirty male SHRs and thirty Wistar rats were randomly divided into four groups：①pMCAO 6 h group （n=6, the rats were euthanized at 6 h after pMCAO）;② Sham operation 6 h group （n=6, the rats were euthanized at 6 h after the sham operation）;③pMCAO 24 h group （n=6, the rats were euthanized at 24 h after pMCAO）;④ Sham operation 24 h group （n=6, the rats were euthanized at 24 h after the sham operation）;⑤Normal group （n=6, the rats were not received any operation）. The pMCAO model was made by the suture-occluded method. The rats were euthanized at either 6 h or 24 h after being assessed the neurological deifcits. Coronal brain slices from the rats at 6 h after pMCAO were subjected to histological observation＆amp;nbsp;with Nissl staining to evaluate the neuronal injury. Continuous coronal brain sections were stained by cresyl violet for the calculation the percentage of infarct volume and evaluation of brain edema. Coronal brain sections of the normal group were stained with hematoxylin-eosin to calculate the wall-to-lumen ratio of the cerebral vessels.Results There were no signiifcance in neurological scores among the different strains each time after pMCAO. The neuronal injury in SHRs were more severe than that in Wistar rats at 6 h after pMCAO. SHRs showed increased percentage of infarct volume at 24 h following pMCAO compared with the Wistar rats with significant differences [（28.05±2.38）%vs （25.23±1.33）%,P〈0.05]. However,the brain edema did not differ between the SHRs and the Wistar rats. Wall-to-lumen ratio values increased in arterioles of SHRs compared with the normotensive Wistar rats [（11.46±3.74）%vs （8.73±1.73）%,P〈0.05]. Conclusion The cerebral ischemic injury in SHRs were more severe than that in the age-matched Wistar rats after pMCAO, which may be due to the hypertrophy, stiffness and the impaired vasodilator response of the collateral vessels which may be caused by hypertension.