本文選題：人肝微粒體-小鼠T細(xì)胞聯(lián)合模型 + 氟咯草酮��； 參考：《毒理學(xué)雜志》2017年05期

【摘要】：目的建立人肝微粒-小鼠3T3細(xì)胞聯(lián)合模型,并應(yīng)用該模型評(píng)價(jià)氟咯草酮代謝后的體外細(xì)胞毒性。方法以環(huán)磷酰胺和他莫西芬分別作為代謝增毒和代謝減毒的模型藥物,建立人肝微粒體-小鼠3T3細(xì)胞聯(lián)合模型。首先將環(huán)磷酰胺和他莫西芬分別配制成一系列濃度的工作溶液,加入人肝微粒體系孵育180 min后離心,將上清液與培養(yǎng)基1∶1混合獲得孵育液。將孵育液與未經(jīng)代謝的細(xì)胞供試液同時(shí)給予小鼠3T3細(xì)胞,給藥48 h后,開(kāi)展CCK-8試驗(yàn),利用測(cè)得的吸光度(A)值,計(jì)算細(xì)胞供試液及孵育液的半數(shù)抑制濃度IC50以及IC50比值,并以IC50比值為指標(biāo)評(píng)價(jià)模型藥物的代謝毒性。待測(cè)化合物氟咯草酮采用與模型藥物相同的方法。結(jié)果環(huán)磷酰胺IC50比值大于535.31%,經(jīng)人肝微粒體代謝后對(duì)3T3細(xì)胞毒性顯著增加。他莫西芬IC50比值小于5.58%,經(jīng)代謝后對(duì)3T3細(xì)胞毒性顯著降低。符合二者作為代謝增毒和代謝減毒代表性藥物的特征。氟咯草酮IC50比值大于391.38%,表明經(jīng)代謝后對(duì)3T3細(xì)胞毒性增加。結(jié)論成功建立人肝微粒-小鼠3T3細(xì)胞聯(lián)合模型。待測(cè)化合物氟咯草酮經(jīng)代謝后毒性增加,為進(jìn)一步的毒理學(xué)研究提供參考依據(jù)。
[Abstract]:Objective to establish a joint model of human liver microparticles - mouse 3T3 cells and to evaluate the cytotoxicity of fluoxacetone in vitro. Methods cyclophosphamide and tamoxifen were used as model drugs for metabolic and metabolic detoxification, respectively, to establish a human liver microsomal mouse 3T3 cell combination model. First, cyclophosphamide and his Mo Xifen were used. The incubation solution was centrifuged after 180 min incubation with the human liver microparticle system. The incubating solution was mixed with the medium of 1: 1. The incubated liquid and the unmetabolized cells were given the test solution for the mice 3T3 cells. After the drug was given 48 h, the CCK-8 test was carried out, and the measured absorbance (A) values were used to calculate the cell test. The half inhibitory concentration of IC50 and the ratio of IC50 to the liquid and incubation fluid, and the evaluation of the metabolic toxicity of the model drug with the IC50 ratio. The results of the same method as the model drug of fluoxacetone to be measured. The results showed that the IC50 ratio of cyclophosphamide was greater than 535.31%, and the toxicity of 3T3 cells increased significantly after the metabolism of human liver microsomes. The IC50 ratio of tamoxifen. The value was less than 5.58%, and the toxicity of 3T3 cells decreased significantly after metabolism. Two were the characteristics of the metabolic and metabolic detoxification representative drugs. The IC50 ratio of flurokroacetone was greater than 391.38%, indicating that the toxicity of 3T3 cells increased after metabolism. Conclusion the combined model of human liver microparticles in mouse 3T3 cell was successfully established. The toxicities increased after the test, providing reference for further toxicological research.
【作者單位】： 上海市食品藥品檢驗(yàn)所藥理毒理室/藥物安全評(píng)價(jià)中心;復(fù)旦大學(xué)公共衛(wèi)生學(xué)院;
【基金】：國(guó)家自然科學(xué)基金(81373040)
【分類號(hào)】：R965

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