中枢CRH在大鼠应激性体温升高和LPS性发热机制中的作用

目的:进一步观察中枢促肾上腺皮质激素释放激素(CRH)在大鼠应激性体温升高和脂多糖(LPS)性发热中枢机制中的作用。方法:第三脑室微量注射CRH受体拮抗剂α-helicalCRH(9-41)和LPS,测定大鼠结肠温度及脑腹中隔区精氨酸加压素(AVP)含量。结果:生理盐水对照组大鼠体温明显升高,最大升幅为(0.88±0.31)℃。第三脑室注射CRH受体拮抗剂α-helicalCRH(9-41)10min后再注射生理盐水组,90min内大鼠结肠温度未见明显波动,90min后体温开始上升,1.5h体温反应指数(TRI_1.5)明显低于生理盐水对照组,而脑腹中隔区AVP含量和TRI_3.5与对照组比较均没有明显差别。第三脑室注射300ng的LPS引起大鼠结肠温度双相性升高,其TRI_3.5明显高于生理盐水对照组。事先向第三脑室注射α-helicalCRH(9-41)(5μg)再注射LPS组,TRI_3.5明显高于LPS组,而脑腹中隔区AVP含量明显低于LPS组。结论:CRH介导应激诱导的早期体温升高。CRH可能通过诱导脑腹中隔区AVP的生成限制大鼠LPS性发热。在大鼠LPS性发热中,CRH可能是一种双相作用分子,一方面本身介导发热体温升高,另一方面又诱生发热体温负调节介质而限制发热体温的升高。

The central role of corticotropin-releasing hormone in stress-induced hyperthermia and LPS-induced fever in rats

AIM: To further investigate the role of centralcorticotropin-releasing hormone in stress-induced hyperthermia and lipopolysaccharide (LPS)-induced fever in the rat. METHODS: Test substances were administered intracerebroventricularly (icv) via a third ventricle cannula. Body temperature responses were monitored at 30 min intervals using colonic thermistor probes. Arginine vasopressin (AVP) level in the ventral septal area (VSA) determined by radioimmunoassay. RESULTS: In normal saline controls, rats were handled to take the colonic temperature, their body temperature significantly increased with a peak of （0.88±0.31）℃. The injection (icv) of α-helical CRH(9-41), a CRH-41 receptor antagonists, markedly attenuated the stress-induced hyperthermia within 90 min after injection of normal saline. LPS(300 ng, icv) stimulated a biphasic rise in the colonic temperature, the 3.5 h thermal response index (TRI3.5) and AVP levels in the VSA of LPS-treated rats were higher than those of control rats. The AVP responses to LPS were inhibited significantly by blockade of central CRH actions using α-helical CRH(9-41) (5 μg ,icv) administered 10 min prior to LPS, while α-helical CRH(9-41) (5 μg ,icv) resulted in exacerbated febrile responses to LPS(300 ng, icv). CONCLUSION: Central CRH plays an important role in stress-induced hyperthermia. The injection (icv) of α-helical CRH(9-41) enhances markedly LPS-induced fever in rats. CRH is a dual action molecule in LPS-induced fever, which itself mediates LPS-induced fever, at the same time, and limits the rise in body temperature during fever through actions of AVP in the VSA and glucocoticoids.