目的:研究纳米雄黄药物对昆明小鼠急性毒性靶器官及病理损害机制,评价其安全性。方法:将32只小鼠随机分为对照组和纳米雄黄实验3 d组、7 d组、14 d组,每组8只。对照组灌胃给予生理盐水,实验组灌胃给予纳米雄黄混悬液5 000 mg/kg,每天1次;实验组小鼠分别在给药后第3、7、14天处死,对照组小鼠在14天处死,观察其一般情况、体重变化并进行血生化指标测定及病理评价。结果:给药后,对照组和实验组小鼠一般情况、体重均无显著差异。与对照组相比,实验组小鼠白蛋白、白球比、尿素氮降低(P＜0.05);7 d组总胆固醇升高(P＜0.05);14 d组碱性磷酸酶升高(P＜0.01)。病理观察发现实验组小鼠肝细胞胞质疏松化、胞浆内出现少量大小不等的透亮的空泡;肺泡结构轻度破坏,肺泡间隔增宽;脾脏红髓和白髓界稍不清,红髓区内出现显著巨核细胞。结论:小鼠灌胃给予纳米雄黄5 000 mg/kg时未见明显急性毒性反应,证明纳米雄黄的安全性较好。
Objective: To study the mechanism of acute toxic target organs and pathological damage of nano-realgar drugs in Kunming mice, and to evaluate its safety. Methods: Thirty-two mice were randomly divided into control group and nano-realgar experimental 3 days group, 7 days group and 14 days group, with 8 mice in each group. The control group was given normal saline by gavage, and the experimental group was given nano-realgar suspension 5 000 mg/kg by gavage, once a day. The mice in the experimental group were sacrificed on the 3rd, 7th and 14 th day after administration, and the mice in the control group were sacrificed on the 14th day. The general condition, body weight change, blood biochemical index determination and pathological evaluation were observed. Results: After administration, there was no significant difference in general condition and body weight between the control group and the experimental group. Compared with the control group, the albumin, albumin-to-globulin ratio and urea nitrogen in the experimental group were decreased (P＜0.05), the total cholesterol in the experimental 7 days group was increased (P＜0.05), and the alkaline phosphatase in the experimental 14 days group was increased (P＜0.01). Pathological observation showed that the cytoplasm of hepatocytes in the experimental group was loose, and a small number of translucent vacuoles of different sizes appeared in the cytoplasm; the alveolar structure was slightly damaged and the alveolar septum was widened; the boundary between red pulp and white pulp of the spleen was slightly unclear, and significant megakaryocytes appeared in the red pulp area. Conclusion: There is no obvious acute toxicity when mice are given by gavage at 5 000 mg/kg, which proves that the safety of nanorealgar is good.
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