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钒化合物作为抗糖尿病药物具有巨大的发展潜力。但是,钒化合物的毒性,尤其是在糖尿病的长期给药中对肾的副作用,限制了其进一步的临床应用。本课题组此前合成了具有良好降血糖作用和低急性毒性的新型抗糖尿病钒化合物BSOV。为了推进BSOV应用和抗糖尿病钒化合物研究的进展,我们以非糖尿病ICR小鼠和II型糖尿病db/db小鼠为对象并以BMOV为对照,对BSOV的长期毒性和降糖效果进行了观察。实验结果确认了两种钒化合物在实验期间(6–7个月)都具有稳定的降糖效果。然而,钒化合物的长期使用在ICR小鼠会轻度增强机体的氧化应激,而在糖尿病小鼠则可能会诱发肾间质水肿,这一作用伴随了明显的血清白蛋白偏低。通过饮食中补充抗氧化剂(维生素C和葡萄糖酸锌)能够消除小鼠的氧化应激现象,但对于肾间质水肿则无明显改善作用。相对于BMOV,BSOV所导致的肾间质水肿发生率明显降低,说明BSOV是向抗糖尿病钒化合物最终成功跨出的重要一步。
Vanadium compounds have tremendous potential as antidiabetic drugs. However, the toxicity of vanadium compounds, especially in the long term administration of diabetes, has limited their further clinical application. Our group had previously synthesized a new type of anti-diabetic vanadium compound BSOV with good hypoglycemic effect and low acute toxicity. To promote the progress of BSOV and anti-diabetic vanadium compounds, we investigated the long-term toxicity and hypoglycemic effects of BSOV in non-diabetic ICR mice and type II diabetic db / db mice and using BMOV as a control. The experimental results confirm that both vanadium compounds have a stable hypoglycemic effect during the experiment (6-7 months). However, long-term use of vanadium compounds in the ICR mice mildly enhances oxidative stress in the body, whereas in diabetic mice it may induce renal interstitial edema accompanied by significant lower serum albumin. Supplementation of dietary antioxidants (vitamin C and zinc gluconate) can eliminate the phenomenon of oxidative stress in mice, but no significant improvement for renal interstitial edema. BSOV caused a significant reduction in the incidence of renal interstitial edema relative to BMOV, suggesting that BSOV is a significant step toward the ultimate success of anti-diabetic vanadium compounds.