蒺藜皂苷对局灶性脑缺血大鼠炎症反应和血脑屏障通透性的影响∗

摘要

Objective To explore the effects of gross saponins of Tribulus terrestris L.on inflammatory reaction and permeability of blood-brain barrier in rats following cerebral ischemia-reperfusion injury and their potential mechanisms. Methods Sixty SD rats were divided into sham operation group,model control group,gross saponins of Tribulus terrestris L.at low-dose (10 mg•kg-1 )and high-dose groups(30 mg•kg-1 ).Cerebral ischemia -reperfusion model was established with suture emboli method in middle cerebral artery of rats.Neural injury scores,the contents of Evans blue ( EB) and myeloperoxidase( MPO) activities in rat brain were measured 24 hours after the cerebral reperfusion post 2 h ischemia.Content of tumor necrosis factor-α (TNF-α) in rat brain was detected by ELISA; expression levels of matrix metalloproteinase-9(MMP-9) in rat brain was determined by Western blot. Results Compared to the model control group,the neurological deficit scores were significantly decreased(P<0.05),MPO activities and EB contents decreased(P< 0.05 or P< 0.01) in the treatment groups.The expression levels of TNF-α were significantly lower in the treatment groups(0.760±0.110) mg•g-1 and (0.670±0.073) mg•g-1 compared to (0.920±0.128) mg•g-1 in the model control group ( P< 0.05 or P< 0.01). The MMP-9 expression levels were (1.770± 0.181)% and(1.480±0.146)%,significantly lower than(2.200±0.186)% in the model control group(P<0.01). Conclusion Gross saponins of Tribulus terrestris L. exert neuroprotective effects on cerebral ischemia-reperfusion injury in rats through inhibiting the inflammatory reaction and decreasing the permeability of blood-brain barrier,which may be associated with the decrease of the TNF-α content and downregulation of the MMP-9 expression.%目的：探讨蒺藜皂苷对大鼠脑缺血-再灌注损伤炎症反应和血脑屏障通透性的作用及其机制。方法斯泼累格•多雷(SD)大鼠60只,随机分为假手术组、模型对照组、蒺藜皂苷小剂量组(10 mg•kg－1)、蒺藜皂苷大剂量组(30 mg•kg－1),每组15只,采用线栓法制备脑缺血-再灌注损伤模型。缺血2 h 再灌注24 h 后分别检测大鼠神经功能损伤评分、缺血脑组织髓过氧化物酶(MPO)的活性和伊文思蓝(EB)的含量；采用酶联免疫吸附测定(ELISA)法检测脑组织肿瘤坏死因子-α(TNF-α)的含量,免疫印记法检测基质金属蛋白酶-9(MMP-9)的表达变化。结果与模型对照组比较,蒺藜皂苷小、大剂量组大鼠神经功能损伤减轻(P<0.05),缺血脑组织 MPO 活性和 EB 含量均明显降低(P<0.05或 P<0.01),TNF-α含量明显降低[分别为(0.760±0.110),(0.670±0.073) mg•g－1,模型对照组为(0.920±0.128) mg•g－1,P<0.05或 P<0.01)],MMP-9的表达水平均明显降低[分别为(1.770±0.181)％,(1.480±0.146)％,模型对照组为(2.200±0.186)％,P<0.01]。结论蒺藜皂苷对大鼠脑缺血-再灌注损伤的脑组织具有神经保护作用,其机制可能与降低 TNF-α含量和下调 MMP-9表达,从而降低炎症反应和血脑屏障通透性有关。