Comparative Study Of The Mouse Model Of Systemic Anaphylactoid Reaction And The Mouse Model For Assay Of Pseudoallergy

Objective:To systematically compare The mouse model of systemic anaphylactoid reaction(MSAR)to The mouse model for assay of pseudoallergy(MAP),In this study,c48/80,tween-80,polyoxyethylene castor oil(Cr EL),iodohexol,paclitaxel,Xuesaitong for injection(freeze-dried)and Shuanghuanglian(freeze-dried)for injection were selected,responsiveness of each index of the two methods to the induction of anaphylactoid reactions induced by the subjects,correlation between each index and dosage of drug administration,based on the sensitivity,specificity and clinical consistency of the comprehensive evaluation results of each built-in index and common index,a comprehensive comparison was made.At the same time,(Rat basophilic leukemia cells,RBL-2H3)cell model of rat basophilic leukemia cells was used to analyze the influencing factors of the difference between two kinds of anaphylactoid reactions.Method:(1)After intravenous injection of positive substance C48/80,MSAR was used to evaluate the symptoms and detect blood histamine,?-hexosaminidase and trypsin,and MAP was used to measure the blue staining,symptom evaluation and blood biomarker histamine.The responsiveness of each built-in index and its correlation with dose were analyzed,and the evaluation results of each built-in index based on MSAR and MAP methods,as well as the evaluation results of common index systemic symptoms and blood histamine test were compared.Two methods were used to evaluate the characteristics of C48/80 type hypersensitivity assessment.(2)Tween-80 and Cr EL,iodohydrin,paclitaxel,Xuesaitong for injection(freeze-dried)and Shuanghuanglian(freeze-dried)for injection were selected as the research objects to detect the effects of intravenous injection on the indexes of MSAR and MAP.On this basis,the characteristics of each built-in index and common index of the two methods were analyzed and compared according to the first section,C48/80.The sensitivity,specificity and clinical consistency of the two methods were analyzedand compared with each other in terms of sensitivity,specificity and clinical consistency of the two methods.The applicability of the two methods to the allergic assessment of the tested substances was evaluated.(3)RBL-2H3 cell model was used to detect histamine levels in the supernatant containing EB(in vitro equivalent dose 0.011 % EB)and non-EB-induced degranulation and release of RBL-2H3 cells.Comparison and preliminary analysis of the possible effect of EB on the release of active substances from RBL-2H3 cells after injecting blood with anaphylaxis positive substances.Results:(1)MSAR is superior to MAP;in evaluating the sensitivity of mice to anaphylactoid reactions induced by C48/80 by both built-in indexes and common indexes.Symptom observation and blood histamine detection can be introduced into MAP,and the sensitivity is better than its built-in index.It can be used as an index to judge the occurrence of anaphylaxis-like reaction in MAP.(2)Judging by two methods of built-in indicators,the sensitivity of Tween-80,Cr EL,iodohydrin injection,Xuesaitong and Shuanghuanglian to anaphylaxis in mice was better than that of MAP;according to the common indexes of the two methods,MSAR was superior to MAP in the sensitivity of mice to anaphylactoid reactions induced by Xuesaitong and iodohydrin;according to the built-in index and the new introduction index of MAP,the sensitivity of tween-80,Cr EL,iodohydrin and Shuanghuanglian to allergic reaction in mice was better than that of built-in index,and the sensitivity of paclitaxel built-in index was better than that of newly introduced index,the sensitivity of Xuesaitong is similar.(3)The mixture of EB and C48/80,affects the degree of degranulation and release of histamine from RBL-2H3 cells,but is inconsistent with the results of in vivo experiments.It needs to be further studied.The trend of degranulation and histamine release from RBL-2H3 cells induced by the mixture of EB and Xuesaitong or Cr EL is similar to that in vivo,but whether it affects the degree of histamine release needs to be further studied.Conclusion:(1)Sensitivity comparison: the sensitivity of MSAR was significantly higher than that of MAP,when the initial dose of positive allergic reaction or the minimum dosewhich was significantly different from the control group was used as the index to evaluate the sensitivity of the two methods.(2)The sensitivity comparison of the same detection index: taking symptom intensity coefficient and blood histamine as the common evaluation index,the two methods showed that the index increased with the increase of the dosage of the drug,showing a significant dose-effect relationship,and there was a significant dose-effect relationship between the two methods.However,the sensitivity of MSAR was significantly higher than that of MAP.(3)These results suggest that MSAR is superior to MAP,recommendation in showing dose-response relationship of anaphylactoid reactions and in detecting sensitivity.(4)The addition of EB affected the degree of anaphylactoid reactions induced by drugs in RBL-2H3 cells.