[Animal modeling]-Occupational asthma model induced by methyl toluene diisocyanate
[Modeling mechanism]: Formaldehyde diisocyanate (TDI) is a low molecular chemical substance with only hapten properties in the human body. TDI has obvious obvious mucosal irritation and corrosion. Exposing animals to 1.5 ppm TDI for one or several months can cause animal bronchitis. TDI asthma has been proven to be an immediate IgE-mediated allergy.
[Forming method]: Add the immediately prepared TDI/1,4-dioxane solution to 1% bovine serum albumin (bovine serum albumin, BSA) sodium bicarbonate in an ice bath with a magnetic stirrer. Adjust the pH value of the solution to 8.5. After adjustment for 1 hour, the reaction solution was transferred to a dialysis bag, placed in a fume hood overnight to evaporate the dioxane, and then completely dialyzed with pH 7.4 phosphate buffered saline (PBS). Then use an ultraviolet spectrophotometer to measure the absorption peak at 245m. The prepared antigen is mixed with BCG vaccine and Freund's incomplete adjuvant, and ground into a water-in-oil emulsion for later use.
For animal vaccination, please use white short-haired guinea pigs weighing 250-300 grams. The animals were injected intraperitoneally with 0.5ml of toluene diisocyanate bovine serum albumin binding antigen (TDI-BSA)/complete Freund’s adjuvant (CFA) and TDI-BSA/aluminum hydroxide (AHG). Three weeks later, the immunized animals will be boosted once or twice. The antigen inhalation challenge test was performed 5-8 weeks after the first immunization. First, human serum albumin (HSA) was used to challenge the antigen inhalation challenge test, and TDI-HSA was inhaled after no response. After inhalation of TDI-HSA aerosol with a concentration of 1 mg/ml, 30.8% of the animals showed obvious asthmatic reactions.
[Characteristics of the model]: Under the stimulation of TDI-HSA, the animal's breathing rate increases during an asthma attack, and the breathing range becomes wider, accompanied by coughing, restlessness, and even spastic breathing. 87.5% of TDI-BSA/CFA sensitized animals and 40% of TDI-BSA/AFA sensitized animals can simultaneously show antigen-specific IgE and IgG antibody titers.
[Model Evaluation and Application]: TDI is one of the important occupational asthma. About 5% to 10% of TDI operators will develop occupational asthma. The establishment of this model provides conditions for further research on the immune mechanism of TDI asthma, and can be used to study the occurrence, development and drug prevention of occupational asthma caused by TDI.