摘要
目的探讨蛋白酶活化受体1/4(PAR-1/4)对蛛网膜下腔出血(SAH)后大鼠脑内小胶质细胞活化的影响。方法雄性SD大鼠100只,随机分为sham组、SAH+control siRNA组、SAH+PAR-1 siRNA组、SAH+PAR-4 siRNA组以及SAH+PAR-1/4 siRNA组,每组20只。应用血管内插线法建立大鼠SAH模型,治疗组在术后1h脑室注射相应剂量药物。在SAH后6h和24h,观察了各组大鼠神经功能学缺陷、脑水含量和脑内伊文思蓝含量,同时应用免疫组织化学和Western blotting方法检测了脑内肿瘤坏死因子α(TNF-α)和细胞间黏附分子-1(ICAM-1)的表达。结果单独应用PAR-1siRNA或PAR-4 siRNA均可减轻SAH后大鼠的神经功能缺陷并降低血管通透性(P<0.05),同时脑内小胶质细胞TNF-α和ICAM-1的表达也明显下降。联合应用PAR-1和PAR-4siRNA的治疗效果最为显著。结论 PAR-1/4参与了蛛网膜下腔出血后大鼠脑内小胶质细胞的活化,而PAR-1/4 siRNA可通过抑制两者的活性减少炎性因子的产生,具有显著的神经血管保护作用。
Objective To investigate the role of protease activated receptor-1 and 4 （ PAR-1, PAR-4） in the activation of microglia following subarachnoid hemorrhage （SAH）. Methods One hundred male SD rats were randomly divided into： sham, SAH ＋ control siRNA, SAH ＋ PAR-1 siRNA, SAH ＋ PAR-4 siRNA and SAH ＋ PAR-1/4 siRNA groups, 20 in each group. The drugs were administrated intracerebroventricularly at 1 hour after SAH. At the 6th and 24th hour after SAH, the neurological deficits, brain water content and Evans blue content were evaluated, at the same time, the expression of tumor necrosis factor a （TNF-a） and intercellular cell adhesion molecule-1 （ ICAM-1 ） were also measured by using immunohistochemistry and Western blotting. Results PAR-lsiRNA or PAR-4 siRNA could significantly ameliorate the neurological deficits and decrease vascular permeability （P 〈 0.05 ）. In addition, the expression of TNF-c~ and ICAM-1 was also decreased by PAR-1 siRNA or PAR-4 siRNA treatment. The combination of PAR-land PAR-4 siRNA played more powerful roles than either of them. Conclusion PAR-1 and 4 mediate the activation of microglia in the brain following SAH. Through suppressing the expression of inflammatory factors, PAR-1 siRNA and/or PAR-4 siRNA play neurovascular protective roles in the brain following SAH.
出处
《解剖学报》
CAS
CSCD
北大核心
2012年第3期306-311,共6页
Acta Anatomica Sinica
基金
国家自然科学基金资助项目(30901548
30971527)
