罗格列酮对大鼠蛛网膜下腔出血后迟发性血管痉挛的防治机制

Rosiglitazone ondelayed cerebral vasospasm after subarachnoid hemorrhage of rats

  • 摘要: 目的 研究罗格列酮对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后迟发性脑血管痉挛(delayed cerebral vasospasm,DCVS)的防治及其与TLR4/NF-κB信号通路的关系。 方法 取45只清洁级的成年雄性Sprague-Dawley (SD)大鼠,随机分为对照组(n=15)、SAH组(n=15)和罗格列酮组(n=15)。罗格列酮组采用枕大池二次注血方案制作SAH动物实验模型,在2次注血前后1 h,腹腔注射罗格列酮(3 mg/kg,溶剂为10%二甲亚砜,0.5 mg/ml);对照组也采用枕大池注射方案,注射等量0.9%氯化钠注射液及经腹腔注射等体积二甲亚砜;SAH组模型建立后,等体积的二甲亚砜注射。SAH模型制备成功后第7天,选取各组大鼠基底动脉标本,苏木素-伊红(HE)染色观察大鼠基底动脉痉挛的情况及病理变化,Western blot技术检测基底动脉TLR4和IL-6的表达。 结果 SAH组较对照组基底动脉管径明显减小,壁厚明显增大(P< 0.01);罗格列酮组较SAH组基底动脉管径增大、壁厚减小(P< 0.01);Western blot检测的结果表明,同SAH组比较,罗格列酮组TLR4、IL-6的表达水平显著降低(P< 0.01)。 结论 罗格列酮通过抑制TLR4/NF-κB信号传导通路,降低TLR4、IL-6等炎性因子在基底动脉中的表达缓解SAH后DCVS。

     

    Abstract: Objective To explore the preventive treatment of rosiglitazone ondelayed cerebral vasospasm (DCVS) after subarachnoid hemorrhage (SAH) in rats and its relationship with TLR4/NF-κB signaling pathways. Methods Forty-five adult healthy male SD rats were randomlydivided into SAH model group (n=15), control group (n=15) and rosiglitazone group (n=15). For rosiglitazone group, autologous blood was injected into the rats' cisterna magna to establish SAH animal model, rosiglitazone (3 mg/kg, with solvent of 10%dimethyl sulfoxide, 0.5 mg/ml) was intraperitoneally injected at 1 hour before and after the first and second bloodinjection. For control group, the equal volume of 0.9% sodium chloride injection was injected and the equal volume ofdimethyl sulfoxide was injected intraperitoneally. For SAH group, the equal volume ofdimethyl sulfoxide was injected intraperitoneally after the establishment of SAH model. Sevendays after injection, the basilar artery spasm was observed with HE staining and the basilar arterydiameter, arterial wall thickness were examined. Western blot was used to examine basilar artery's expression of TLR4 and IL-6. Results Thediameter of basilar artery were significantly smaller in SAH group and the thickness of arterial wall in SAH group significantly increased when compared with normal group (P< 0.01). Compared with SAH group, the basilar arterydiameter in rosiglitazone group increased and the thickness of arterial walldecreased (P< 0.01). Western blot showed that when compared with SAH group, expression of TLR4 and IL-6decreased significantly in rosiglitazone group (P< 0.01). Conclusion Rosiglitazone can inhibit TLR4/NF-κB signaling pathways, thus alleviatingdCVS after SAH and reducing the expression of TLR4, IL-6 in basilar artery.

     

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