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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 effect of PAR-1/4 on the activation of microglia in rat brain after subarachnoid hemorrhage (SAH). Methods 100 male SD rats were randomly divided into sham group, SAH + control siRNA group, SAH + PAR-1 siRNA group, SAH + PAR-4 siRNA group and SAH + PAR- . SAH model was established by intravascular interpolation. The rats in the treatment group were injected intracerebroventricular injection of the corresponding dose of drugs at 1 hour after operation. At 6h and 24h after SAH, neurological deficit, brain water content and brain Evans blue content in each group were observed. Immunohistochemistry and Western blotting were used to detect the levels of tumor necrosis factor-α (TNF-α ) And intercellular adhesion molecule-1 (ICAM-1). Results PAR-1 siRNA alone or PAR-4 siRNA reduced the neurological deficits and decreased the vascular permeability (P <0.05) in SAH rats. Meanwhile, the expression of TNF-α and ICAM-1 in intracerebral microglia Also significantly decreased. The combination of PAR-1 and PAR-4 siRNA treatment of the most significant effect. Conclusions PAR-1/4 is involved in the activation of microglia in rat brain after subarachnoid hemorrhage. PAR-1/4 siRNA can reduce the production of inflammatory cytokines by inhibiting the activity of both, with significant nerve Vascular protection.