摘要
目的:研究前列腺素受体Ⅲ型(EP3)受体激动剂硫前列酮(Sul)致热大鼠下丘脑蛋白激酶A(PKA)、蛋白激酶C(PKC)活性的变化及桂枝汤的解热作用机制。方法:选用Sul 1 mg.kg-1脑室注射(icv)致大鼠发热,观察H-89(特异性PKA抑制剂)1 mg.kg-1(icv),calphostin C(特异性PKC抑制剂)1 mg.kg-1(icv)和桂枝汤10 g.kg-1(ig)对模型大鼠发热的影响,继而采用放射性同位素法,测定给予桂枝汤后EP3受体激动剂致热大鼠下丘脑组织中PKA,PKC的活性变化。结果:Sul脑室注射后,呈现单峰的发热曲线,峰值时在注射后0.5 h左右,并伴有下丘脑组织中PKA活性显著增高和PKC活性的降低倾向。PKA,PKC抑制剂及桂枝汤均可使模型大鼠的发热曲线下移;口饲桂枝汤能显著抑制造模动物下丘脑PKA的活性,大剂量桂枝汤还能显著降低PKC的活性。结论:下丘脑组织中的PKA,PKC参与了EP3致大鼠发热的病理过程,桂枝汤可抑制EP3激动诱致的PKA活性增高,这可能是桂枝汤解热作用靶点之一。
Objective： To investigate the changes of the activity of both protein kinase A and C and the mechanisms of antipyretic action of Guizhi decoction. Method： The fever responses were observed after combination injection of H-89 （a selective inhibitor of PKA） and calphostin C （a selective inhibitor of PKC）, and oral pretreatment of Guizhi decoction in fever rats induced by an intra-cerebroventrictdar （icv） injection of an EP3 agonist, and both PKA and PKC activity in hypothalamus were measured in rats pretreated with Guizhi decoction and vehicle using isotopic tracing assay. Result： The rise in rat body temperature was inhibited by H-89, Calphostin C, and Guizhi decoction, moreover, pretreatment with Guizhi decoction reduced PKA activity obviously. PKC activity in model rats exhibited a tendency to drop compared with that of control group, Oral administration of Gnizhi decoction in large dose inhibited the response significantly, while the low dose of Guzhi decoction has no effect on PKC. Conclusion： Both PKA and PKC may participate in the mechanism of fever induction by EP3 agonist. The decrease of PKA and PKC may contribute to the antipyretic action of Guizhi decoction, some isoenzyme of PKC may play a role in the fever production.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2006年第1期66-69,共4页
China Journal of Chinese Materia Medica
基金
国家自然科学基金重大研究计划(90209006)
