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目的 观察cAMP依赖性蛋白激酶信号传导通路在大鼠CRH性发热机制中的作用。方法 第三脑室注射促肾上腺皮质激素释放激素 (CRH) ,腺苷酸环化酶抑制剂DDA或cAMP依赖性蛋白激酶抑制剂Rp cAMPS ,测定大鼠结肠温度。用放射免疫分析法测定下丘脑cAMP含量 ,并用离体实验观察CRH对下丘脑cAMP含量的影响。结果 第三脑室微量注射CRH(2 5 μg ,5 0 μg ,10 μg)引起大鼠结肠温度和下丘脑cAMP水平明显升高 ,下丘脑cAMP水平与大鼠 2小时发热反应指数之间存在明显的正相关 (r=0 994 ,P <0 0 1)。离体实验同样观察到CRH可引起下丘脑cAMP水平明显升高。事先向第三脑室微量注射腺苷酸环化酶抑制剂DDA 30 μg或cAMP依赖性蛋白激酶抑制剂Rp cAMPs 15 μg均显著抑制中枢注射CRH引起的发热反应。结论 这些结果证明 ,cAMP参与了大鼠CRH性发热的中枢机制 ,cAMP依赖性蛋白激酶可能在CRH性发热机制中发挥重要作用 ,cAMP依赖性蛋白激酶信号传导通路可能介导中枢注射CRH对大鼠的致热作用。
Objective To investigate the role of cAMP-dependent protein kinase signaling pathway in CRH-induced fever in rats. Methods The third ventricle was injected with corticotropin-releasing hormone (CRH), adenylyl cyclase inhibitor DDA or cAMP-dependent protein kinase inhibitor Rp cAMPS to determine the colonic temperature in rats. The content of cAMP in the hypothalamus was measured by radioimmunoassay, and the effect of CRH on cAMP content in the hypothalamus was observed in vitro. Results Microinjection of CRH into the third ventricle (25 μg, 50 μg, 10 μg) induced a significant increase in colonic temperature and cAMP level in hypothalamus. The cAMP level in hypothalamus was significantly different from that in 2 hours Positive correlation (r = 0 994, P <0.01). In vitro experiments also observed CRH can cause hypothalamic cAMP levels were significantly increased. Microinjection of adenosine cyclase inhibitor DDA 30 μg or cAMP-dependent protein kinase inhibitor Rp cAMPs 15 μg into the third ventricle beforehand significantly inhibited central febrile CRH-induced fever. Conclusions These results demonstrate that cAMP is involved in the central mechanism of CRH-induced fever in rats. CAMP-dependent protein kinase may play an important role in the mechanism of CRH fever. The cAMP-dependent protein kinase signaling pathway may mediate central CRH injection in rats The pyrogenic effect.