以PNP酶為靶點(diǎn)的急性高尿酸血癥小鼠模型組建
發(fā)布時(shí)間：2018-10-21 14:46
【摘要】：目的建立一種新的急性高尿酸血癥小鼠模型并利用該模型對PNP酶抑制劑Ulodesine進(jìn)行體內(nèi)藥效作用評價(jià)。方法小鼠腹腔注射肌苷(inosine)和皮下注射氧嗪酸鉀(oteracil potassium)誘導(dǎo)體內(nèi)尿酸蓄積,在一定時(shí)間段內(nèi)對小鼠進(jìn)行內(nèi)眥靜脈或摘眼球采血,測定血清尿酸值,判斷小鼠急性高尿酸血癥模型成功與否;再利用酶動(dòng)力學(xué)分析Ulodesine對PNP酶的體外抑制作用,并于造模前給予小鼠灌胃Ulodesine,造模后測定血清尿酸值,評價(jià)Ulodesine的降血尿酸作用。結(jié)果小鼠腹腔注射200 mg·kg~(-1)肌苷聯(lián)合皮下注射200 mg·kg~(-1)氧嗪酸鉀在1.5 h時(shí)能形成較為穩(wěn)定的急性高尿酸血癥;酶動(dòng)力學(xué)測定結(jié)果顯示Ulodesine對PNP酶有極強(qiáng)的抑制作用,其IC_(50)值為2.293 nmol·L~(-1);另外,Ulodesine的體內(nèi)藥效表明,Ulodesine能夠明顯減低急性高尿酸血癥小鼠體內(nèi)尿酸水平。結(jié)論我們已經(jīng)成功地建立了一種新的急性高尿酸血癥小鼠模型,該造模制作方法更簡單有效,且該模型可以應(yīng)用于驗(yàn)證PNP酶抑制劑。
[Abstract]:Objective to establish a new mouse model of acute hyperuricemia and evaluate the in vivo pharmacodynamics of PNP enzyme inhibitor Ulodesine. Methods the accumulation of uric acid in mice was induced by intraperitoneal injection of inosine (inosine) and subcutaneous injection of potassium oxazinate (oteracil potassium). The blood samples were collected from the inner canthus vein or eyeball of the mice in a certain period of time, and the serum uric acid levels were measured. To judge the success of acute hyperuricemia model in mice, to analyze the inhibitory effect of Ulodesine on PNP enzyme in vitro by enzyme kinetics, and to determine the serum uric acid value after mice were given Ulodesine, before making model, and to evaluate the effect of Ulodesine on reducing uric acid. Results after intraperitoneal injection of 200 mg kg~ (-1) inosine and subcutaneous injection of 200 mg kg~ (-1) potassium oxazinate, stable acute hyperuricemia was formed in mice, and the results of enzyme kinetics test showed that Ulodesine had a strong inhibitory effect on PNP enzyme. Its IC_ _ (50) value was 2.293 nmol L ~ (-1). In addition, the in vivo pharmacodynamics of Ulodesine showed that Ulodesine could significantly reduce the level of uric acid in mice with acute hyperuricemia. Conclusion We have successfully established a new acute hyperuricemia mouse model. The method is simpler and more effective, and the model can be used to verify the PNP enzyme inhibitor.
【作者單位】： 昆藥集團(tuán)股份有限公司藥物研究院生物學(xué)部;
【基金】：云南省科技廳高層次科技創(chuàng)新人才計(jì)劃(No 2013HA018)
【分類號】：R-332;R965
本文編號：2285422
[Abstract]:Objective to establish a new mouse model of acute hyperuricemia and evaluate the in vivo pharmacodynamics of PNP enzyme inhibitor Ulodesine. Methods the accumulation of uric acid in mice was induced by intraperitoneal injection of inosine (inosine) and subcutaneous injection of potassium oxazinate (oteracil potassium). The blood samples were collected from the inner canthus vein or eyeball of the mice in a certain period of time, and the serum uric acid levels were measured. To judge the success of acute hyperuricemia model in mice, to analyze the inhibitory effect of Ulodesine on PNP enzyme in vitro by enzyme kinetics, and to determine the serum uric acid value after mice were given Ulodesine, before making model, and to evaluate the effect of Ulodesine on reducing uric acid. Results after intraperitoneal injection of 200 mg kg~ (-1) inosine and subcutaneous injection of 200 mg kg~ (-1) potassium oxazinate, stable acute hyperuricemia was formed in mice, and the results of enzyme kinetics test showed that Ulodesine had a strong inhibitory effect on PNP enzyme. Its IC_ _ (50) value was 2.293 nmol L ~ (-1). In addition, the in vivo pharmacodynamics of Ulodesine showed that Ulodesine could significantly reduce the level of uric acid in mice with acute hyperuricemia. Conclusion We have successfully established a new acute hyperuricemia mouse model. The method is simpler and more effective, and the model can be used to verify the PNP enzyme inhibitor.
【作者單位】： 昆藥集團(tuán)股份有限公司藥物研究院生物學(xué)部;
【基金】：云南省科技廳高層次科技創(chuàng)新人才計(jì)劃(No 2013HA018)
【分類號】：R-332;R965
【相似文獻(xiàn)】
相關(guān)期刊論文 前1條
1 徐立;時(shí)樂;趙芳;譚秋薇;姚金梁;;大鼠急性高尿酸血癥模型的復(fù)制方法初探[J];中國藥理學(xué)通報(bào);2007年07期
，本文編號：2285422
本文鏈接：http://sikaile.net/yixuelunwen/yiyaoxuelunwen/2285422.html
最近更新
教材專著
