探究不同剂量硫辛酸注射液热原反应的影响  

Effect of Pyrogen Reaction in Different Doses of Lipoic Acid Injection

作　　者：曾令伟 刘昱廷 赵亚绘 ZENG Lingwei;LIU Yuting;ZHAO Yahui(Department of Pharmacy,Xiangya Hospital,Central South University,Changsha,Hunan Province,410008 China)

机构地区：[1]中南大学湘雅医院药学部,湖南长沙410008

出　　处：《系统医学》2023年第4期36-40,共5页Systems Medicine

摘　　要：目的对硫辛酸注射液不良反应加以研究,重点分析该药物所致热原反应的原因,提供给临床更多的用药安全性参考。方法2022年3—6月于中南大学医院药学研究所以新西兰兔11只作为药物实验动物开展研究,设计药物毒理试验,同时将实验动物分为两组,即硫辛酸注射液实验样品(观察组3只,按照30 mg/kg剂量给药)和硫辛酸注射液对照样品(对照组3只,按照10 mg/kg剂量给药),对两组兔子采用热原反应检查法分别注射加热后的硫辛酸药物,分别测定两组兔子体内温度升高水平,复检以完成热原试验,标记体温升高超过0.6℃的兔子,判断两组热原反应阳性结果,初检阳性情况下另外取5只兔子进行复检;接着采用细菌内毒素检测法(鲎试剂)判断致热原是否为内毒素;再依据体内外溶血试验分析溶血反应与热原反应之间的联系。结果观察组热原检查试验阳性;内毒素与热原反应联系不大;体外溶血试验中观察组阳性;体内溶血试验中注射前观察组兔子血浆游离血红蛋白(Hb)为(46.15±9.17)g/L,注射后(128.54±11.76)g/L,差异有统计学意义(t=55.098,P<0.001),注射后观察组Hb水平较对照组更高,差异有统计学意义(t=9.313,P<0.001)。结论细菌内毒素并不会引起硫辛酸注射液热原反应的发生,而实验样品在30 mg/kg注射剂量条件下可致热原反应呈现阳性结果,过程中实验兔子体内外发生了溶血反应,可能与热原反应存在内在联系。Objective To study the adverse reactions of lipoic acid injection,to analyze the causes of pyrogen reaction caused by lipoic acid injection,so as to provide more references for drug safety in clinic.Methods The experiment was conducted in the time line from March to June 2022.Eleven New Zealand rabbits were used as drug experimental animals for observation,and the research was carried out in the pharmacy institute of Central South University.Drug toxicology test was designed,and experimental animals were divided into two groups,namely experimental samples of lipoic acid injection(3 samples in the observation group,administered at a dose of 30 mg/kg)and control samples of lipoic acid injection(3 samples in the control group,administered at a dose of 10 mg/kg).Rabbits in two groups were injected with heated lipoic acid by pyrogen reaction test method,and the level of temperature rise in rabbits in two groups was determined respectively,and the pyrogen test was completed by reexamination.Rabbits whose body temperature increased by more than 0.6℃were labeled to determine the pyrogen reaction positive results in the two groups.In the case of positive initial test,another five rabbits were selected for reexamination.Then bacterial endotoxin test(limulus lysate)was used to determine whether pyrogen was endotoxin.Then the relationship between hemolysis reaction and pyrogen reaction was analyzed based on in vivo and in vitro hemolysis test.Results Pyrogen test was positive in the observation group,endotoxin was not closely related to pyrogen reaction,and the observation group was positive in the in vitro hemolysis test.In vivo hemolysis test,plasma free hemoglobi(Hb)in observation group was(46.15±9.17)g/L before injection and(128.54±11.76)g/L after injection,and the difference was statistically signifiDOI:10.19368/j.cnki.2096-1782.2023.04.036cant(t=55.098,P<0.001).After injection,Hb level in the observation group was higher than that in the control group,and the difference was statistically significant(t=9.313,P<0.001

关 键 词：硫辛酸注射液 剂量 热原反应 溶血 内毒素 

分 类 号：R965[医药卫生—药理学]