蛋白酶激活受体-3在大鼠体内外脑缺血模型中的作用研究

Protease activated receptor-3 on in vivo and in vitro rat models of ischemic stroke

目的研究蛋白酶激活受体-3(PAR-3)在大鼠体内外脑缺血模型中的作用。方法以PAR-3激活肽(AP)为工具药,采用大脑中动脉阻塞和氧糖剥夺法分别建立大鼠和大鼠胚胎脑皮质神经元缺血模型,观察PAR-3在缺血损伤中的作用及表达变化。用肌动描记器记录PAR-3对大鼠大脑中动脉(MCA)血管张力的影响,用蛋白印迹法研究PAR-1对PAR-3表达的影响。结果 PAR-3在缺血侧大脑皮质和神经元中无显著改变,PAR-1 AP和拮抗剂对PAR-3的表达无影响。缺血前给予PAR-3 AP SFNGGP-NH2显著改善了体内缺血模型导致的损伤,但对体外缺血模型导致的损伤无影响,它能够显著收缩来自正常或缺血大鼠的MCA。结论 SFNGGP-NH_2有望作为预防性治疗脑缺血疾病的靶点进行研究,但不是通过受体数量的调节起作用,胶质细胞或其他类型细胞可能在保护机制中起到更重要的作用。

Objective To determine the effect of protease activated receptor-3 （PAR-3） on in vivo and in vitro rat models of ischemic stroke. Methods The effect and expression of PAR-3 were investigated with PAR-3 activating peptide （AP） in rat ischemic stroke models, which were established by middle cerebral artery occlusion and oxygen glucose deprivation. The effect of PAR-3 on vascular tension of middle cerebral artery （MCA） was observed with myograph. The effect of PAR-1 on the expression of PAR-3 was studied as well. Results Western blot showed that there was no obvious expression change of PAR-3 in the ipsilateral brain cortex of rats and cortical neurons subjected to ischemia, the presence of PAR-1 AP or PAR-1 antagonist. Pretreatment of SFNGGP-NH2 protected damages induced by ischemia only in vivo study but not in vitro, and obviously elicited vasoconstriction in MCA in both normal or ischemic rats. Conclusion PAR-3 AP SFNGGP-NH2 is identified as a promising target for the development of novel prophylactic treatment of ischemic brain disease, which may not function through the regu- lation of receptor number. Glial cells or other cell types may contribute more to the protection than the neurons.