硒代硫酸钠在充分安全剂量下可显著保护由顺铂引起的胃肠毒性

发布时间：2018-01-23 07:10

本文关键词： 顺铂胃肠毒性亚硒酸硒代硫酸肿瘤　出处：《安徽农业大学》2012年硕士论文　论文类型：学位论文

【摘要】：我们以前对于小鼠的研究表明，两周时间内，硒代硫酸钠的短期毒性明显低于亚硒酸钠，，然而这两种化合物中硒的生物利用却相同。另外，我们还发现，硒代硫酸钠在不影响顺铂的抗癌作用下，可以降低由其引起的肾毒性，由此可以使癌症治愈率从25%提高到75%。临床实践中，广泛采用水化作用的方法用于降低由顺铂引起的肾毒性，但这种方法却不能减轻由顺铂引起的胃肠毒性。因此本研究探讨硒代硫酸钠是否为一种潜在的可以缓和胃肠毒性的保护剂。在荷瘤小鼠体内，每天注射剂量为9.5μmol/kg硒代硫酸钠，连续注射11天，单独顺铂组在第12天导致了88%的小鼠腹泻，然而顺铂和硒代硫酸钠的合并组的小鼠腹泻率却只有6%（P0.0001）。如此显著的保护作用提示我们去评估长期使用硒代硫酸钠的安全性。于是在小鼠腹腔内注射剂量分别为12.7和19μmol/kg的硒代硫酸钠或亚硒酸钠，并连续注射55天。结果发现亚硒酸钠低剂量组引起了小鼠生长抑制和肝毒性，高剂量组这种现象加剧并导致了40%的死亡率，然而注射硒代硫酸钠的两组均未观察到中毒症状。所有这些结果清晰地表明，硒代硫酸钠在无毒剂量下可以有效预防由顺铂引起的胃肠毒性。
[Abstract]:Our previous studies in mice have shown that the short-term toxicity of sodium selenosulfate is significantly lower than that of sodium selenite in two weeks, but the bioavailability of selenium in these two compounds is the same. Sodium selenosulfate can reduce the renal toxicity caused by cisplatin without affecting the anticancer effect of cisplatin, and thus the cure rate of cancer can be increased from 25% to 75.4 in clinical practice. Hydration is widely used to reduce nephrotoxicity caused by cisplatin. However, this method can not reduce the gastrointestinal toxicity caused by cisplatin. Therefore, this study is to explore whether sodium selenosulfate is a potential protective agent for gastrointestinal toxicity in tumor-bearing mice. Sodium selenosulfate was injected at a daily dose of 9.5 渭 mol/kg for 11 days. In the cisplatin group alone, diarrhea was caused in 88% mice on the 12th day. However, the diarrhea rate of mice in the combination group of cisplatin and sodium selenosulfate was only 6g / P0.0001). Such a significant protective effect suggests that we should assess the safety of long-term use of sodium selenosulfate. Then intraperitoneal injection of sodium selenosulfate or selenite at the doses of 12.7 and 19 渭 mol/kg, respectively, was made in mice. Sodium. The results showed that the low dose sodium selenite group caused the growth inhibition and hepatotoxicity in mice, which was aggravated in the high dose group and resulted in the death rate of 40%. However, no toxic symptoms were observed in the two groups injected with sodium selenosulfate. All these results clearly indicate that sodium selenosulfate can effectively prevent gastrointestinal toxicity caused by cisplatin at nontoxic doses.
【学位授予单位】：安徽农业大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R151.3

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