本文選題：MNT- + Sprague-Dawley大鼠　； 參考：《軍事醫(yī)學(xué)》2017年06期

【摘要】：目的研究大鼠灌胃MNT-016重復(fù)染毒90 d的毒性反應(yīng),為其毒性評價提供參考資料。方法設(shè)玉米油為對照溶劑,MNT-016以5、20、80 mg/kg連續(xù)90 d灌胃給予SD大鼠,進行臨床癥狀、體質(zhì)量、血液學(xué)、血液生化學(xué)及病理組織學(xué)等檢查;觀察動物出現(xiàn)的毒性效應(yīng),獲得未觀察到有害作用劑量(NOAEL);通過基準(zhǔn)劑量法求得基準(zhǔn)劑量的可信限下限值(BMDL)。結(jié)果與溶劑對照組相比,雄性動物AST、TBIL、DBIL、Crea呈劑量依賴性升高,TG、CHOL呈降低趨勢;高劑量組雄性動物體質(zhì)量(解剖前)、心臟、肝臟、胸腺、附睪質(zhì)量顯著降低,腦系數(shù)、肺臟系數(shù)顯著升高;雌性動物體質(zhì)量(解剖前)及胸腺質(zhì)量顯著降低,肺臟系數(shù)顯著升高。高劑量組可致肝細胞空泡變性、腎小管嗜堿性病變,中、低劑量組可致肝細胞空泡變性、個別腎小管萎縮,雄性動物病變發(fā)生率更高。結(jié)論 MNT-016的NOAEL值雄性動物小于5 mg/kg體質(zhì)量,雌性動物為5 mg/kg體質(zhì)量。BMDL值雄性動物為2.65 mg/kg,比相應(yīng)NOAEL更準(zhǔn)確;雌性動物為9.04 mg/kg,略大于相應(yīng)的NOAEL。
[Abstract]:Objective to study the toxicity of MNT-016 repeated exposure to 90 d in rats, and to provide reference materials for its toxicity evaluation. Methods corn oil was used as a control solvent and MNT-016 was given to SD rats with 5,20,80 mg/kg for 90 d, and the clinical symptoms, body mass, hematology, hematology and histopathology were examined, and the toxicity of the animals was observed. Effect, obtain unobserved dose of harmful dose (NOAEL); obtain the confidence limit value (BMDL) of baseline dose by reference dose. Results compared with the solvent control group, male animals AST, TBIL, DBIL, Crea were dose-dependent, TG, CHOL showed a decreasing trend; high dose group male body mass (before dissection), heart, liver, thymus, epididymis The mass of the body mass (before dissection) and the mass of the thymus significantly decreased and the lung coefficient increased significantly. The high dose group could cause the vacuolation of the hepatocyte and the basophilic tubule of the renal tubules, and the low dose group could cause the vacuolation of the hepatocytes, some renal tubules atrophy and the incidence of the male animal disease. Conclusion the NOAEL value of MNT-016 is less than 5 mg/kg body mass, and the female animal is 2.65 mg/kg with 5 mg/kg body mass.BMDL, and the female animal is more accurate than the corresponding NOAEL; the female animal is 9.04 mg/kg, slightly larger than the corresponding NOAEL..

【作者單位】： 沈陽藥科大學(xué)生命科學(xué)與生物制藥學(xué)院;解放軍疾病預(yù)防控制所毒理學(xué)評價研究中心;北京衛(wèi)生職業(yè)學(xué)院;
【基金】：國家自然科學(xué)基金重點資助項目(81430090)
【分類號】：R99

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