家兔静脉注射羟基磷灰石纳米粒子的反应研究

Toxicity of hydroxyapatite nanoparticles on rabbits

目的探讨纳米羟基磷灰石微晶体(HAP)对家兔静脉应用的急性毒性反应及剂量。方法对50只新西兰大白兔经耳缘静脉快速推注不同浓度的纳米HAP混悬液,观察家兔用药前后的反应,死亡情况;并检测纳米HAP对家兔肝肾功及酶等指标的影响。结果纳米HAP静脉应用对家兔的最小致死剂量(LD1)为180mgkg,半数致死剂量LD50为200mgkg,全死剂量LD99为260mgkg。AST,LDH,CKC及P在用药后2h呈一过性增高,而于24h内即恢复正常。BUN,ALP则在24h时增高达最高峰,随后迅速下降至正常范围,其余指标均基本维持在正常值范围内。结论纳米HAP在家兔无明显蓄积毒性,提示当用量远远小于最小致死剂量时,纳米HAP可作为药物载体,甚至在将来可能作为一种新型的抗癌药物,经静脉安全应用。

Objective\ To study the toxicity of nano-hydroxyapatite on rabbits by vein. Methods The hydroxyapatite solution was intravenous injected into 50 New Zealand white rabbits with different concentration, then to observe the reactions and the survial rates of rabbits, and to investigate the effects of nano-HA to the liver function,renal function, enzyme and Ca,Mg,P. Results The medium lethal dosege of nano-HA administrated intravenous^iv) was determined as 200mg/kg. The level of phosphorous increased but calcium and magnesium kept stable. LDH, CPK, GOP and GDT dramatically increased in 30 minutes after injection, arriving the peak at 2 hours later, however, they all returned to normal 24h after injection. BUN and ALP got to the peak at 24 hours later, then decreased rapidly to normal level. The other indexes almost maintained at normal level. Conclusion Nano-hydroxyapatite has no accumulative toxicity to rabbits, it is suggested that it is safe when the hydroxyapatite-sol was applied intravenously as a drug carrier in small dosage more less than the medium lethal dose, even as a kind of anticancer drug.