本文關(guān)鍵詞： 羅非昔布 花生四烯酸 環(huán)氧酶抑制劑 前列腺素 HETE　出處：《大連醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：羅非昔布為特異性環(huán)氧化酶-2抑制藥，有抗炎、鎮(zhèn)痛作用，持續(xù)服用羅非昔布的患者中發(fā)生確定的心血管事件（如高血壓、腦卒中等）的相對危險性顯著增加。羅非昔布以及同類藥物（如：塞來昔布）致心血管風(fēng)險機(jī)制的研究日益引起重視。本研究旨在分析羅非昔布對花生四烯酸代謝產(chǎn)物血漿含量的影響，從而探討羅非昔布導(dǎo)致心血管風(fēng)險的可能機(jī)制，為其他同類藥物的臨床安全使用提供參考。 方法：將雄性C57小鼠隨機(jī)分組為對照組、足腫脹組和羅非昔布組。在所有處置之前測小鼠足部厚度。足腫脹組和羅非昔布組于足部皮下注射1%角叉菜膠；羅非昔布組于注射角叉菜膠前1小時腹腔注射羅非昔布20mg/kg；對照組于相應(yīng)時間注射生理鹽水。處置完成2小時后測小鼠足部厚度、取血及足部組織。將足組織做病理切片、染色、顯微鏡下觀察病理切片形態(tài)學(xué)變化。采用BCA蛋白濃度測定試劑盒及小鼠腫瘤壞死因子(tumornecrosisfactor-α，TNF-α)ELISA試劑盒測定小鼠足組織和血漿中的TNF-α含量，采用超高壓液相色譜-串聯(lián)質(zhì)譜（ultrahighpressureliquidchromatography-tandemmassspectrometry，UPLC-MS/MS）測定血漿中花生四烯酸代謝產(chǎn)物6-酮-前列腺素F1α(6-keto-prostaglandinF1α，，6-keto-PGF1α)、前列腺素E2(prostaglandinE2，PGE2)、白三烯B4（leukotrieneB4，LTB4)、8-羥-二十烷四烯酸（8-hydroxy-eicosatetraenoicacid，8-HETE）、11-羥-二十烷四烯酸（11-hydroxy-eicosatetraenoicacid，11-HETE）、12-羥-二十烷四烯酸（12-hydroxy-eicosatetraenoicacid，12-HETE）以及8,9-環(huán)氧二十碳三烯酸(8,9-epoxyeicosatrienoicacid，8,9-EET)的含量。采用統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析。 結(jié)果：足腫脹組小鼠足部組織病理切片顯微鏡下示：大量炎性細(xì)胞浸潤，組織明顯水腫，提示角叉菜膠制造模型成功；羅非昔布組小鼠足組織腫脹顯著改善。與足腫脹組小鼠相比，羅非昔布組血漿6-keto-PGF1α、PGE2、11-HETE含量顯著降低（p0.01、p0.05、p0.05）；與對照組相比，羅非昔布組血漿LTB4、8-HETE、12-HETE、8,9-EET含量亦顯著降低（p0.01、p0.01、p0.05）。 結(jié)論：羅非昔布可顯著降低足腫脹小鼠花生四烯酸的代謝產(chǎn)物PGI2、PGE2、8-HETE、11-HETE、12-HETE以及8,9-EET的血漿含量；且此作用可能與其心血管風(fēng)險發(fā)生的機(jī)制有關(guān)。
[Abstract]:Objective: rofecoxib is a specific cyclooxygenase-2 inhibitor with anti-inflammatory and analgesic effects, and certain cardiovascular events (such as hypertension) occur in patients who continue to take rofecoxib. The relative risk of stroke was significantly increased. The mechanism of cardiovascular risk caused by rofecoxib and similar drugs (such as celecoxib) has attracted increasing attention. The purpose of this study was to analyze the effects of rofecoxib on arachidonic acid. The effect of the content of Xie product on plasma, To explore the possible mechanism of cardiovascular risk caused by rofecoxib, and to provide reference for the safe use of other similar drugs. Methods: male C57 mice were randomly divided into control group, foot swelling group and rofecoxib group. The foot thickness was measured before all the treatments. 1% carrageenin was injected subcutaneously into the foot in the foot swelling group and rofecoxib group. Rofecoxib group was injected rofecoxib 20 mg / kg one hour before carrageenin injection, and control group was injected with normal saline at the corresponding time. Foot thickness, blood and foot tissue were measured 2 hours after disposal. BCA protein concentration assay kit and tumor necrosis factor- 偽 (TNF- 偽) Elisa kit were used to detect the content of TNF- 偽 in mouse foot tissue and plasma. Determination of arachidonic acid metabolites 6-keto-prostaglandin F1 偽 6-keto-prostaglandin F1 偽 6-keto-PGF 1 偽, prostaglandin F 1 偽 6-keto-PGF 1 偽, prostaglandin E 2 prostaglandin PGE 2 偽, leukotrienol B4 leukotrieneB4LTB4- 8-hydroxy-hydroxy-eicosatetraenoacididine 8-HETEX 11-hydroxy-#number1# keto-prostaglandin F _ 1 偽, prostaglandin E _ 2 (PGE _ 2), leukotrienotrieneB _ 4 (LTB4) -8-hydroxy-hydroxy-eosatetraenoacididine (8-hydroxy-hydroxy-#number1# enoacidate) in plasma, prostaglandin F _ (1 偽) 6-keto-PGF _ (1 偽), prostaglandin E _ 2 (PGE _ (2)), leukotriene B _ (4) (LTB _ 4) -8-hydroxy-eosoic acid traenoacididine (8-hydroxy--#number1# enoic acid). The contents of enoic acid (12-hydroxy-eicosatetraenoic acididine) and 89-epoxyeicosatrienoic acididine (89-EET-89-EET-89-epoxyeicosatrienoic acididine) were analyzed by statistical software. Results: in the foot swelling group, the pathological sections of the feet showed that a large number of inflammatory cells infiltrated and the tissues were obviously edema, which suggested that carrageenin was a successful model. Rofecoxib group significantly improved the swelling of podocyte tissue. Compared with the paw swelling group, the plasma 6-keto-PGF1 偽 PGE2F1-HETE content in rofecoxib group was significantly lower than that in rofecoxib group, and the content of plasma LTB48-HETE12-HETE89-EET in rofecoxib group was also significantly lower than that in rofecoxib group. Conclusion: rofecoxib can significantly reduce the plasma levels of PGI2PGE28-HETETE-11-HETETE-12-HETE and 89-EET in paw swelling mice, and this effect may be related to the mechanism of its cardiovascular risk.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R965

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相關(guān)期刊論文 前2條

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