医疗器械亚慢性毒性试验SD大鼠生理指标历史对照参考值范围的建立

Establishment of Historical Reference Values for Physiological Indexes of SD Rats in Subchronic Toxicity Test of Medical Devices

目的:建立亚慢毒性SD大鼠体重、脏器重量、脏器系数、血液学、凝血和血清生化等指标的正常参考值范围,为医疗器械亚慢性毒性试验提供参考依据。方法:以本实验室近两年(2021年8月~2023年8月)的医疗器械亚慢性毒性试验的阴性对照组动物(300只,雌雄各半)为数据来源,均采取尾静脉注射生理盐水的给药方式,剂量为10mL/kg,连续注射28d,称重后采血和解剖,检测血液学、凝血和血清生化学等指标,对心、肝、脾、肾、肾上腺、胸腺、脑、雄性(睾丸、附睾)、雌性(子宫、卵巢)等脏器进行称重并计算脏器系数,各指标雌雄之间进行统计学分析,以x±1.96s确定95%正常参考值范围。结果:雄鼠和雌鼠在体重和脏器重量均有显著差异;脏器系数方面,肝、肾上腺、胸腺、脑有显著差异;血液学和凝血方面,除PLT外其他指标均有显著差异;血清生化方面,Alb、ALP、ALT、AST、TCHO、GLU、TP、TG、BUN、K^(+)、Na^(+)和Cl^(-)均有显著差异,在体重、脏器重量、脏器系数、血液学、凝血和血清生化方面雌雄之间的CV值都相对一致。结论:本研究建立的SD大鼠生理指标正常参考值范围可为医疗器械亚慢性毒性试验提供参考依据。

Objective:To establish the normal reference values of body weight,organ weight,organ coefficient,hematology,coagulation and serum biochemical indexes in SD rats with subchronic toxicity,so as to provide a reference for subchronic toxicity test of medical devices.Methods:The negative control group of 300 animals(half male and half female)in the subchronic toxicity test of medical devices conducted in our laboratory in the past two years(August 2021 to August 2023)is used as the data source.Normal saline was injected through tail vein for consecutive 28 days at a dose of 10mL/kg.After weighing,blood samples were collected and dissected to detect hematology,coagulation and serum biochemistry indexes.Organs such as heart,liver,spleen,kidney,adrenal gland,thymus,brain,male(testis,epididymis),female(uterus,ovary)were weighed and organ coefficients were calculated.Statistical analysis was performed between male and female indicators,and the 95%normal reference value range was determined by x±1.96s.Results:There were significant differences in body weight and organ weight between male and female rats.In terms of organ coefficient,there were significant differences in liver,adrenal gland,thymus and brain.There were significant differences in hematology and coagulation except platelet(PLT).In terms of serum biochemistry,there were significant differences in Alb,ALP,ALT,AST,TCHO,GLU,TP,TG,BUN,K^(+),Na^(+) and Cl^(-).The CV values of body weight,organ weight,organ coefficient,hematology,coagulation and serum biochemistry were relatively consistent between males and females.Conclusion:The normal reference value range of physiological indexes in SD rats established in this paper can provide a reference for subchronic toxicity test of medical devices.