摘要
目的分析安宫牛黄丸干预脓毒症急性肺损伤小鼠的剂量与时机,为临床治疗提供启示与思路。方法研究分为预实验和正实验两部分。预实验分为模型组和对照组,模型组采用脂多糖(LPS)(20 mg/kg)腹腔注射进行脓毒症造模,对照组腹腔注射生理盐水(20 ml/kg),观察造模后小鼠生存状态,要求模型组死亡率达到50%~80%,对照组死亡率为0%。正实验分两部分开展:剂量研究与时机研究。剂量研究分为模型组、对照组、干预组,模型组、干预组LPS腹腔注射造模脓毒症急性肺损伤,对照组腹腔注射生理盐水。干预组根据安宫牛黄丸使用剂量不同分4组:半剂量组(0.2275 g·kg^(-1)·d^(-1))、单剂量组(0.455 g·kg^(-1)·d^(-1))、双倍剂量组(0.91 g·kg^(-1)·d^(-1))、四倍剂量组(1.82 g·kg^(-1)·d^(-1)),于造模开始同时鼻饲安宫牛黄丸。时机研究分为模型组、对照组、干预组,造模方法与剂量研究部分相同,干预组根据安宫牛黄丸用药时间的不同分为5组:0 h组、6 h组、12 h组、18 h组、24 h组,按照时间要求鼻饲最佳剂量安宫牛黄丸。观察所有小鼠生存状态并记录死亡情况,以安宫牛黄丸最佳疗效为目标筛选1组,观察肺组织病理切片图。结果预实验,采用LPS(20 mg/kg)腹腔注射造模的小鼠,符合脓毒血症模型成功标准,3组小鼠死亡率均为80%,对照组全部存活。正实验剂量研究部分,7 d存活率分别为:模型组20%、对照组100%、干预组52.5%(半剂量组60%、单剂量组70%、双倍剂量组50%、四倍剂量组30%);Kaplan-Meier生存分析P=0.0099。时机研究部分,7 d存活率分别为:模型组20%、对照组100%、干预组42%(0 h组70%、6 h组50%、12 h组40%、18 h组40%、24 h组10%),Kaplan-Meier生存分析P=0.0046。结论LPS(20 mg/kg)腹腔注射造模的脓毒症小鼠,死亡率可达80%,操作简单,稳定性及可重复性高,安宫牛黄丸干预脓毒症小鼠的最佳剂量为0.455 g/kg,起始最佳干预时机为0 h。
Objective To analysis optimal dose and timing of Angong Niuhuang pills in treating of mice with acute lung injury in sepsis,to provide insights and ideas for clinical therapy.Methods The study was divided into two parts:pre-experiment and positive experiment.Pre-experiment was divided into model group and control group.the model group were modeled for sepsis by intraperitoneal injection of LPS(20 mg/kg),the control group were injected intraperitoneally by saline(20 ml/kg).The survival status of mice after modeling was observed,and the mortality rate was required to be controlled at 50%to 80%in the model group and 0%in the control group.The positive experiment was carried out in two parts:dose study and timing study.Dose study was divided into model group,control group,and intervention group.Model group and the intervention group LPS were injected intraperitoneally to model septic acute lung injury.Control group was injected intraperitoneally with saline.Intervention group was divided into four groups according to the different doses of Angong Niuhuang pills used:half-dose group(0.2275 g·kg^(-1)·d^(-1)),single-dose group(0.455 g·kg^(-1)·d^(-1)),double-dose group(0.91 g·kg^(-1)·d^(-1)),and quadruple-dose group(1.82 g·kg^(-1)·d^(-1)),each group were administered Angong Niuhuang pills nasally at the same time as start of modeling.Timing study was also divided into model group,control group and intervention group.The modeling method was the same as that of the dose study,and the intervention group was divided into five groups according to the different dosing times of Angong Niuhuang pills:0 h group,6 h group,12 h group,18 h group and 24 h group,each group were administered optimal dose of Angong Niuhuang pills nasally according to the time requirement.All mice were observed for survival status and outcome.1 group was screened with goal of optimal efficacy of Angong Niuhuang pills.Histopathological section images of lungs were observed.Results In pre-experiment,mice modeled by intraperitoneal injection of LPS(20 mg/kg)met the success criteria for sepsis modeling,with a mortality rate of 80%in all three groups,and 100%survive in control group.For positive experimental dose study portion,7-day survival rates were 20%in model group,100%in control group,and 52.5%in intervention group(60%in half-dose group,70%in single-dose group,50%in double-dose group,and 30%in quadruple-dose group).Kaplan-Meier:P=0.0099.For timing study portion,7-day survival rates were 20%in model group,100%in control group,and 42%in intervention group(70%in 0 h group,50%in 6 h group,40%in 12 h group,40%in 18 h group,and 10%in 24 h group).Kaplan-Meier:P=0.0046.Conclusion LPS(20 mg/kg)intraperitoneal injection method for septic mice modeled with 80%mortality is simple,stable and reproducible.The optimal dose of Angong Niuhuang pills for intervention in septic mice is 0.455 g/kg,and the optimal time for starting the intervention is 0 h.
作者
张静
张开源
王天相
申九妹
李缙婷
叶钢福
陈少东
ZHANG Jing;ZHANG Kaiyuan;WANG Tianxiang;SHEN Jiumei;LI Jinting;YE Gangfu;CHEN Shaodong(Department of Respiratory and Critical Care Medicine/Xiamen Key Laboratory of Traditional Chinese Medicine Preparation Research and Transformation,Xiamen Hospital of Traditional Chinese Medicine,Fujian Province,Xiamen 361015,China;不详)
出处
《临床合理用药》
2026年第3期1-4,9,F0003,共6页
Chinese Journal of Clinical Rational Drug Use
基金
2022年厦门市医疗卫生指导性项目(3502Z20224ZD1179)
厦门市第六批中医后备人才项目(厦卫中医〔2022〕136号)
厦门市扶持中医药发展专项(XWZY-2023-0612、XWZY-2025-0512)
国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函〔2022〕1号)。
关键词
安宫牛黄丸
脂多糖
脓毒症
急性肺损伤
用药剂量
用药时机
先证而治
Angong Niuhuang pills
Lipopolysaccharides
Sepsis
Acute lung injury
Dosage
Timing of dosing
E vidence-based treatment
