消炎痛与安乃近对大鼠退热作用的比较研究
A comparative study of the antipyretic effects of indomethacin and dipyrone in rats.
作者信息
De Souza G E P, Cardoso R A, Melo M C C, Fabricio A S C, Silva V M S, Lora M, De Brum-Fernandes A J, Rae G A, Ferreira S H, Zampronio A R
机构信息
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Ribeirão Preto, Brazil.
出版信息
Inflamm Res. 2002 Jan;51(1):24-32. doi: 10.1007/pl00000278.
OBJECTIVE
Compare the antipyretic effects of dipyrone and indomethacin.
MATERIALS AND METHODS
Fever was induced in rats by i. v. LPS or i. c. v. interleukins (IL), prostaglandins (PG), arachidonic acid (AA), pre-formed pyrogenic factor (PFPF), tumour necrosis factor-alpha (TNF-alpha) or corticotrophin releasing hormone (CRH). Dipyrone and indomethacin were administered i.p., arginine vasopressin V1-receptor antagonist, d(CH2)5 Tyr(Me)AVP, into the ventral septal area. Cyclooxygenase (COX-1/-2) blocking activity was assessed in transfected COS-7 cells. CRH release from isolated hypothalami was determined by ELISA.
RESULTS
Indomethacin or dipyrone reduced LPS, IL-1beta, IL-6 or TNF-alpha induced fever and CRH release from rat hypothalamus. Only dipyrone inhibited IL-8, PFPF or PGF2alpha fever. Only indomethacin inhibited fever induced by AA or IL-1beta, plus AA. Neither antipyretic affected fever caused by PGE2 or CRH. d(CH2)5Tyr(Me)AVP only blocked antipyresis induced by indomethacin. Dipyrone at a very high concentration (10 mM) inhibited only COX-1, while indomethacin (0.1 microM) blocked COX-1 and COX-2 in COS-7 cells.
CONCLUSION
The antipyretic effect of dipyrone differs from that of indomethacin in that it does not depend on AVP release or inhibition of PG synthesis.
目的
比较安乃近和吲哚美辛的退热效果。
材料与方法
通过静脉注射脂多糖（LPS）或脑室内注射白细胞介素（IL）、前列腺素（PG）、花生四烯酸（AA）、预形成的致热因子（PFPF）、肿瘤坏死因子-α（TNF-α）或促肾上腺皮质激素释放激素（CRH）诱导大鼠发热。腹腔注射安乃近和吲哚美辛，将精氨酸加压素V1受体拮抗剂d(CH2)5Tyr(Me)AVP注入腹侧隔区。在转染的COS-7细胞中评估环氧化酶（COX-1/-2）阻断活性。通过酶联免疫吸附测定法（ELISA）测定离体下丘脑释放的CRH。
结果
吲哚美辛或安乃近可降低LPS、IL-1β、IL-6或TNF-α诱导的发热以及大鼠下丘脑释放的CRH。仅安乃近可抑制IL-8、PFPF或PGF2α引起的发热。仅吲哚美辛可抑制由AA或IL-1β加AA诱导的发热。两种退热药均不影响由PGE2或CRH引起的发热。d(CH2)5Tyr(Me)AVP仅阻断吲哚美辛诱导的解热作用。高浓度（10 mM）的安乃近仅抑制COX-1，而吲哚美辛（0.1 microM）在COS-7细胞中可阻断COX-1和COX-2。
结论
安乃近的退热作用与吲哚美辛不同，其不依赖于抗利尿激素释放或对前列腺素合成的抑制。
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