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目的:探讨哮喘大鼠下丘脑室旁核(paraventricular nuclei,PVN)内组胺H3受体对下丘脑-垂体-肾上腺轴(HPA)功能的调控。方法:根据Elwood方法,制备哮喘模型。采用中枢立体定位技术,在PVN内微量注射组胺H3受体激动剂R-(α)-甲基组胺[R-(α)-methylhistamine,R-(α)-MeHA]2μg或组胺H3受体拮抗剂Thioperamide 5μg,注射药物体积均为1μl。高效液相色谱法检测PVN内组胺含量;放射免疫分析方法检测正中隆起中促肾上腺皮质激素释放激素(CRH)和外周血中促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量;酶联免疫吸附法(ELISA)检测脑组织和血浆IL-10含量。结果:与生理盐水组相比,R-(α)-MeHA组大鼠PVN内组胺含量明显下降(P<0.01);CORT、ACTH及CRH含量明显增加(P<0.01);IL-10含量增高(P<0.01);Thioperamide可阻断上述效应,差异均有统计学意义。结论:大鼠PVN内组胺H3受体参与调控哮喘的发作,该作用可能与其影响HPA轴功能有关。
AIM: To investigate the regulation of histamine H3 receptor on hypothalamic-pituitary-adrenal axis (HPA) function in paraventricular nuclei (PVN) of asthmatic rats. Methods: According to the Elwood method, an asthma model was prepared. The central stereotaxic technique was used to microinject 2μg histamine H3 receptor agonist R- (α) -methylhistamine [R- (α) -MeHA] or histamine H3 Receptor antagonist Thioperamide 5μg, injection drug volume was 1μl. The content of histamine in PVN was detected by high performance liquid chromatography (RP-HPLC). The contents of adrenocorticotropic hormone releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in peripheral blood were detected by radioimmunoassay The contents of IL-10 in brain tissue and plasma were detected by ELISA. Results: Compared with the saline group, the content of histamine in PVN of rats in R- (α) -MeHA group decreased significantly (P <0.01), the content of CORT, ACTH and CRH increased significantly (P <0.01) (P <0.01); Thioperamide can block the above effects, the differences were statistically significant. Conclusion: The histamine H3 receptor in PVN plays an important role in the pathogenesis of asthma. This effect may be related to its effect on HPA axis function.