背景:葡萄糖酸锌(ZG)是一种安全有效的锌补充剂。然而,关于ZG静脉注射的最佳剂量和动物模型的安全性评价的研究有限。本研究旨在确定ZG用于C57BL/6J小鼠静脉注射的安全剂量范围。
方法:进行剂量滴定实验以确定小鼠中ZG的LD50和95%置信区间(95CI)。基于LD50,评估了ZG的四种亚致死剂量(SLD)。每次注射3次SLD并监测7天后,测量血清锌水平,和肝脏的病理变化,肾,通过组织学染色确定小鼠的脾组织。
结果:剂量滴定实验确定ZG在小鼠体内的LD50为39.6mg/kg,95CI为31.8-49.3mg/kg。在SLD施用后,总体血清锌水平存在统计学显著差异(H=36.912,P<0.001)。两两比较显示,1/2LD50和3/4LD50组血清锌水平明显高于对照组(P<0.001);3/4LD50组血清锌水平明显高于1/8LD50和1/4LD50组(P<0.05)。ZG的不同SLDs与小鼠血清锌水平呈正相关(rs=0.973,P<0.001)。H&E染色显示肝脏无显著组织学异常或病变,肾,和所有实验组小鼠的脾组织。
结论:明确了ZG用于C57BL/6J小鼠静脉注射的适宜剂量范围,为今后的实验研究提供参考。
BACKGROUND: Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice.
METHODS: A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining.
RESULTS: The dose titration experiment determined the LD50 of ZG in mice to be 39.6 mg/kg, with a 95%CI of 31.8-49.3 mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups.
CONCLUSIONS: The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.