血管紧张素Ⅱ-1型受体拮抗剂在脑出血大鼠治疗中的作用

Role of AT1R antagonists in the treatment of cerebral hemorrhage in rats

目的探讨血管紧张素Ⅱ-1型受体(AT1R)拮抗剂在大鼠脑出血治疗中的神经保护作用及机制。方法以胶原酶诱导法建立大鼠脑出血模型48只,随机选取24只应用AT1R拮抗剂奥米沙坦干预治疗为治疗组,24只为未治组。分别在造模成功后的24 h、48 h及72 h处死大鼠,取脑组织。用HE染色观察脑组织病理学变化;用免疫组化及RT-PCR检测两组大鼠各时间点脑组织中血管紧张素Ⅱ(AngⅡ)、AT1R和白细胞抗原CD40配体(CD40L)的表达,并分别采用平均光密度及灰度比值对各指标表达做定量比较。用RT-PCR检测并比较两组大鼠在各时间点脑组织RNA浓度。结果治疗组脑内AngⅡ、AT1R和CD40L在各时间点蛋白和基因表达及RNA浓度值均较未治组低,脑水肿减轻,差异有显著性意义(P<0.05)。结论 AT1R拮抗剂可使脑出血大鼠的炎症因子含量减低,对神经有保护作用。

Objective Discuss the nerve protective effect and mechanism of AT1R blocker in the treatment of cerebral hemorrhage in rats.Methods The ICH model induced via stereotaxic administration of collagenase type Ⅳ were 48,randomly divided into two groups,24 of them were OLM（one kind of AT1R blocker）-treated ICH groups（referred to as treated groups hereinafter）,24 of them were untreated ICH groups,at twenty-four hours,forty-eight hours and seventy-two hours after ICH model were induced,the pathological changes of brain tissue were observed with microscope after HE staining,the related indicators such as AngⅡ,AT1R and CD40L of brain tissue were tested by IHC method and RT-PCR method,and were expressed by the average optical density and the gray level ratio index,the RNA levels of brain tissue were measured by RT-PCR method,and were compared with each other at the same time.Results Compared with the untreated groups,the levels of AngⅡ,AT1R and CD40L were decreased,brain edema relieved,and each index numeric comparisons had statistical significance（P0.05） in the treated groups.Conclusion The levels of related inflammatory factors decreased after AT1R blocker combining with AT1R in the brain tissue of rats with intracerebral hemorrhage,so as to inflammatory reaction reduced and nerve protective effects were played.