本文選題：對(duì)乙酰氨基酚 + 肝損傷�。� 參考：《毒理學(xué)雜志》2015年01期

【摘要】：目的探討血清蘋(píng)果酸脫氫酶(MDH)和嘌呤核苷磷酸化酶(PNP)對(duì)肝損傷早期診斷的應(yīng)用價(jià)值。方法 C57小鼠隨機(jī)分為對(duì)照組、低劑量組、中劑量組和高劑量組,各劑量組分別灌胃給予對(duì)乙酰氨基酚(APAP)200、350和500 mg/kg,對(duì)照組給予生理鹽水。于給藥后不同時(shí)間點(diǎn)(3、6、12和24 h)采集血清,用全自動(dòng)生化分析儀測(cè)定血清谷丙轉(zhuǎn)氨酶(ALT)的水平,紫外分光光度計(jì)測(cè)定血清MDH的水平,ELISA測(cè)定血清PNP的水平。解剖后取肝臟計(jì)算肝指數(shù),并進(jìn)行HE染色,觀察肝組織病理形態(tài)學(xué)變化。結(jié)果與對(duì)照組同時(shí)間點(diǎn)相比,給APAP后3 h,各劑量組MDH均顯著升高(P0.05或P0.01),PNP在中劑量組及高劑量組顯著升高(P0.05或P0.01),ALT則無(wú)明顯變化;給APAP后6 h,各劑量組ALT、MDH和PNP均明顯升高(P0.05或P0.01);給APAP后12 h,中劑量組及高劑量組ALT和MDH顯著升高(P0.01),PNP在各劑量組均顯著升高(P0.01);給APAP后24 h,各指標(biāo)水平均有所下降,和對(duì)照組同時(shí)間點(diǎn)相比,ALT、MDH和PNP僅在高劑量組有顯著性差異(P0.01)。與對(duì)照組相比,各時(shí)間點(diǎn)高劑量組肝指數(shù)均顯著升高(P0.05或P0.01),顯微鏡下肝組織病理切片可見(jiàn)明顯的肝細(xì)胞脂肪變性,高劑量組出現(xiàn)水腫。結(jié)論 MDH和PNP在肝損傷早期ALT沒(méi)有發(fā)生明顯變化時(shí)就顯著升高,具有較好的靈敏性,且變化趨勢(shì)與ALT相同,與病理結(jié)果一致,可以作為APAP致肝損傷早期的生物學(xué)標(biāo)志。
[Abstract]:Objective to investigate the value of serum malate dehydrogenase (MDH) and purine nucleoside phosphorylase (PNPs) in the early diagnosis of liver injury. Methods C57 mice were randomly divided into three groups: control group, low dose group, middle dose group and high dose group. Each dose group was given paracetamol APP 200350 and 500 mg / kg, and the control group was given normal saline. Serum samples were collected at different time points at 12 and 24 hours after administration. Serum alanine aminotransferase (alt) levels were measured by automatic biochemical analyzer. Serum MDH levels were measured by UV spectrophotometer and serum PNP levels were determined by Elisa. After dissection, the liver index was calculated and HE staining was performed to observe the histopathologic changes of the liver. Results compared with the control group at the same time point, at 3 h after APAP, the MDH of each dose group was significantly higher than that of the control group (P 0.05 or P 0.01), but there was no significant difference between the middle dose group and the high dose group (P 0.05 or P 0.01). At 6 hours after APAP, the levels of alt MDH and PNP were significantly increased in each dose group (P 0.05 or P 0.01), and at 12 h after APAP, ALT and MDH in middle dose group and high dose group were significantly increased in all dose groups, and the levels of ALT and MDH were decreased at 24 h after APAP administration, and the levels of ALT and MDH in the middle dose group and high dose group were significantly higher than those in the control group at 24 h after APAP administration, the levels of ALT and MDH in the middle dose group were significantly higher than those in the control group. Compared with the control group, MDH and PNP only showed significant difference in high dose group (P 0.01). Compared with the control group, the liver index of the high dose group was significantly higher than that of the control group (P 0.05 or P 0.01). Steatosis of liver cells could be seen in pathological sections of liver tissue under microscope, and edema appeared in the high dose group. Conclusion MDH and PNP increased significantly at the early stage of liver injury, and had good sensitivity, and the change trend was the same as that of ALT, which could be used as a biological marker in the early stage of liver injury caused by APAP.
【作者單位】： 首都醫(yī)科大學(xué)附屬北京中醫(yī)醫(yī)院檢驗(yàn)科;軍事醫(yī)學(xué)科學(xué)院疾病預(yù)防控制所毒理學(xué)評(píng)價(jià)研究中心;
【基金】：重大新藥創(chuàng)制科技重大專項(xiàng)(2012ZX09J12203-002)
【分類號(hào)】：R994

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