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目的探索经口灌胃纳米银建立肝细胞凋亡动物模型,并初步阐明其发生机制。方法选用2～3月龄长爪沙鼠,随机分成3个剂量试验组和1个生理盐水阴性对照组,每组均为14只,雌性各半,分笼饲养。3个剂量组分别每天按30、125和500 mg/kg体重给予各组小鼠各剂量受试物,对照组小鼠经口灌胃同批号生理盐水,剂量为25 ml/kg,连续28 d。注射结束后第3天,经小鼠眼眶采血,检测小鼠血清超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平,用TUNEL法、流式细胞技术检测肝细胞凋亡情况,并进行光子显微镜、电子显微镜观察,探索导致明显急性肝损伤的可能机制。结果与对照组相比,剂量125和500 mg/kg的受试组血清中SOD活力和GSH-Px活力显著降低(P<0.01),MDA含量显著提高(P<0.01);30mg/kg剂量受试组血清SOD和GSH-Px活力降低,MDA含量提高,但差异不显著(P>0.05);组织病理学检测可见典型的凋亡小体结构;流式细胞术、TUNEL法检测及电镜检测都见明显的凋亡小体。结论注射125 mg/kg剂量以上纳米银的老鼠肝细胞出现了明显的凋亡。
OBJECTIVE To explore the animal model of hepatic cell apoptosis induced by oral administration of nano-silver and clarify its mechanism. Methods Two-and-three-month-old Mongolian gerbils were randomly divided into three dose groups and one saline-negative control group, with 14 females in each group. The three dose groups were given 30,125 and 500 mg / kg body weight of each dose of the test substance in each group, the control group mice were orally administered with the same amount of saline, a dose of 25 ml / kg, for 28 days . On the third day after the injection, blood samples were collected from the orbit of mice to detect the levels of serum superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) Method, flow cytometry detection of hepatocyte apoptosis, and photon microscopy, electron microscopy to explore the possible mechanism leading to significant acute liver injury. Results Compared with the control group, the activity of SOD and the activity of GSH-Px in the serum of 125 mg / kg and 500 mg / kg group were significantly decreased (P <0.01) and the content of MDA was significantly increased (P <0.01) The activities of serum SOD and GSH-Px in the test group decreased and MDA content increased, but the difference was not significant (P> 0.05). The typical apoptotic body structure was observed by histopathological examination. Flow cytometry, TUNEL and electron microscopy See obvious apoptotic bodies. Conclusion There was obvious apoptosis in hepatocytes of mice injected with nano-silver at dose of 125 mg / kg.