MK-801通过抑制RhoA在出血性脑损伤机制的研究

Mechanism of MK-801 in brain injury after intracerebral hemorrhage by inhibiting the expression of RhoA

目的观察大鼠脑出血后血肿周围Rho GTP酶(RhoA)的表达变化及地佐环平(dizo-cilpine,MK-801)对其表达的影响,探讨在脑出血后脑损伤中N-甲基-D-门冬氨酸(N-methyl-D-aspartate,NMDA)与RhoA的相关性。方法 SD雄性大鼠随机分为生理盐水组、出血组和治疗组,采用鼠尾自体血注入尾状核法建立大鼠脑出血3d模型,治疗组用MK-801在脑出血模型前1h腹腔注射,分别用伊文思蓝(Evans blue,EB)测血脑屏障(blood brain barrier,BBB)通透性,干-湿重法测血肿周围脑组织含水量,Western blot法测定患侧RhoA在各组的表达量。结果 MK-801治疗组较脑出血BBB通透性明显降低(P<0.05),血肿周围脑水肿明显减轻(P<0.05),RhoA表达量明显较少(P<0.05)。结论 MK-801能减轻脑出血后脑水肿、血脑屏障的开放,揭示MK-801通过抑制RhoA的表达可能参与出血性脑损伤。

Objective To investigate the correlation of N-metbyl-D-aspartate（NMDA） and RhoA in brain injury after in- tracerebral hemorrhage by observing the expression of RhoA and die affect of MK 801 on the expression in brain of rat suffered from ICH. Methods SD rats were divided randomly into three groups： normal saline group, ICH group, MK-801 ＋ ICH group. Autologous blood（50μL） were injected into the right caudate nucleus in the ICH group, MK-801 were injected into theintraperitoneal one hour before ICH in the MK-801 group. The permeability of blood brain barrier（BBB）was evaluated by Evansblue （EB）contents and the water content of brain was measured by content of wet and dry weight in peri hematoma, the ex- pression of RhoA in each group was measured by Western blot. Results MK-801 significantly reduced the permeability of BBB （P〈0.05）, and significantly decreased the water content of brain（P〈0.05） and lessened the expression of RhoA consequently in rats after intracerebral hemorrhage（P〈0.05）. Conclusion NMDA inhibitor MK-801 can decrease the brain edema and the damage of the permeability of BBB. MK-801 may participate in hemorrhagic brain by inhibiting the expression of RhoA.