机构地区:[1]北京市疾病预防控制中心,北京市食物中毒诊断溯源技术重点实验室,北京100013 [2]首都医科大学公共卫生学院,北京100069
出 处:《毒理学杂志》2023年第2期87-92,107,共7页Journal of Toxicology
基 金:国家重点研发计划(2018YFC1602700,2018YFC1603102,2018YFC1602202)。
摘 要:目的在非临床毒理学安全性评价的动物试验中,血常规与血清生化指标等常作为一般毒性的反映指征,但国内外各标准指南中对于血样的采集方式却没有统一的要求,有时会影响试验结果的准确性。本研究即以氯化锰为受试物,通过短期内连续大剂量暴露于大鼠后,比较其对动脉血与静脉血的血常规及血清生化等指标的影响。方法48只SD大鼠按体重随机分为6组,分别为动脉采血与静脉采血的对照组、低剂量组(25 mg/kg·bw)及高剂量组(50 mg/kg·bw)。低剂量组与高剂量组通过腹腔注射给予MnCl_(2)·4H2O(对照组相同处理给予生理盐水)7 d后,按预定计划采血后分别检测血常规、血清生化及电解质等。结果氯化锰染毒后,大鼠的体重明显下降且具有剂量依赖性(F=22.904,F=18.897,P<0.01);低剂量组主要引起动脉血MCV、MCH、MONO%、ALT、AST、UREA、CREA的下降与PLT、Cl^(-)的升高(P<0.05),而静脉血则表现为MCV、MCH、ALT、ALB、CREA的下降以及NEUT%、PLT与Na^(+)的升高(P<0.05);高剂量组主要引起动脉血MCV、MCH、MONO%、ALT、AST、UREA、CREA的下降与RBC、HGB、HCT、NEUT%、CHOL、Ca^(2+)、Cl^(-)的升高(P<0.05),而静脉血则表现为MCV、MCH、ALT、ALB、CREA的下降(P<0.05);析因分析提示,氯化锰处理是引起RBC、HGB、HCT、MCV、MCH、NEUT%、PLT、ALT、AST、GLU、ALB、CREA、CHOL、Ca^(2+)、Na^(+)与Cl^(-)差异的主要因素(P<0.05),而采血方式则是引起RBC、HGB、HCT、AST、GLU、ALB、TP、UREA、CREA、Ca^(2+)、K^(+)、Na^(+)与Cl^(-)差异的主要因素(P<0.05)。结论氯化锰作用下,动脉血与静脉血样中红细胞系、肝功能相关指标、肾功能相关指标以及电解质等的变化均有一定的差别,相比较而言,动脉血能更好地反映氯化锰作用下血液中各临床指标的变化。Objective Blood routine and serum biochemical indexes are often used as general toxicity indicators in the animal experiments of non-clinical toxicological safety evaluation.However,there are no uniform requirements for blood collection method in various standard guidelines both at home and abroad,which sometimes affect the accuracy of experimental result.In this study,manganese chloride was used as the test substance to compare its effects on blood routine and serum biochemical indexes of arterial and venous blood after a short period of continuous high dose exposure to rats.Methods Forty-eight SD rats were randomly divided into six groups according to body weight,including control group,low-dose group(25 mg/kg·bw)and high-dose group(50 mg/kg·bw)for arterial and intravenous blood collection,with eight rats in each group.The low-dose group and high-dose group were given intraperitoneal injection of MnCl_(2)·4H_(2)O(the control group was given normal saline in the same treatment)for seven days,and blood routine,serum biochemistry and electrolytes were detected respectively after blood collection according to the scheduled plan.Results After exposure to manganese chloride,the body weight of rats decreased significantly in a dose-dependent manner(F=22.904,F=18.897,P<0.01).In low dose group,the content of MCV,MCH,MONO%,ALT,AST,UREA and CREA in arterial blood decreased but PLT and CL increased(P<0.05),and in venous blood,MCV,MCH,ALT,ALB and CREA were decreased but NEUT%,PLT and Na^(+)were increased(P<0.05).In high dose group,the contents of MCV,MCH,MONO%,ALT,AST,UREA and CREA were decreased but RBC,HGB,HCT,NEUT%,CHOL,Ca22+*and CIwere increased(P<0.05),and in venous blood,MCV,MCH,ALT,ALB and CREA were decreased(P<0.05).Factorial analysis suggested that manganese chloride treatment was the main factor causing the difference of RBC,HCB,HCT,MCV,MCH,NEUT%,PLT,ALT,AST,GLU,ALB,CREA,CHOL,Ca^(2+),Na^(+)and Cl^(-)(P<0.05),whereas,blood collection method was the main factor that caused the difference of RBC,HGB,HCT,AST,CLU,AL
分 类 号:R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]
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