Study On The Safety Of Long-term Atomized Inhalation Of Non-atomized Drug In Lung Tissue Of SD Rats

Objective:To study the injury of respiratory tract of SD rats after long-term atomization inhalation of non aerosol formulations.Methods:40 healthy male SD rats of SPF grade were randomly divided into the blank control group(no atomization),the saline group(0.9% sodium chloride injection 10ml),the budesonide group(1mg/2ml budesonide suspension + 0.9% sodium chloride injection 8ml),the Dingchuan Decoction group(10ml),the ceftriaxone group(2g/10ml),the Qingkailing group(10ml),the Tanreqing group(10ml),the silica group(400mg/10ml)a total of 8 groups,5 in each group,were atomized 2 times a day for 56 days.Then,peripheral blood and bronchoalveolar lavage fluid were collected and used for cell count,percent of each type of cell.HE staining was used to observe the pathological changes of lung tissue and count the number of dust cells.Immunohistochemistry was applied to detect the exprssion of CD163 in lung.Results:(1)The results of peripheral blood leukocyte count in each group: blank group < normal saline group < budesonide group < Tanreqing group < Qingkailing group < Ceftriaxone group < Dingchuan Decoction group < silica group,F = 42.55,P < 0.01.F=3.51,P > 0.05 between blank control group,saline group and budesonide group.Peripheral blood lymphocyte count: blank group < normal saline group < budesonide group < Tanreqing group < Ceftriaxone group < Qingkailing group < Dingchuan Decoction group < silica group.There was no significant difference among the blank control group,saline group and budesonide group(F = 1.58,P > 0.05).There was significant difference between the other five groups(P < 0.01).There was significant difference between the first three groups and the last five groups(P < 0.01).(2)Leukocyte count in alveolar lavage fluid: blank group < normal saline group < budesonide group < Tanreqing group < Ceftriaxone group < Qingkailing group < Dingchuan Decoction group < silica group;There was no significant difference between the blank control group,saline group and budesonide group(P > 0.05).There was significant difference between the five groups each other(P < 0.01).There was significant difference between the first three groups and the last five groups.(3)HE staining of lung tissue blank control group,saline group,budesonide group bronchial and pulmonary tissue integrity,other groups have varying degrees of alveolar wall thickening,alveolar interstitial edema,alveolar cavity and interstitial lung can be seen in varying amounts of dust cells,lymphocyte proliferation.HE staining dust cell count in lung tissue: blank control group < normal saline group < budesonide group < Tanreqing < Ceftriaxone group < Qingkailing group < Dingchuan Decoction group < silica group,the first three groups and the last five groups were statistically different(P < 0.05).(4)Immunohistochemical of CD163 responging: blank control group,saline group,budesonide group showed negative expression,Tanreqing group,Qingkailing group,ceftriaxone group showed positive expression,Dingchuan Decoction group and silica group showed strong positive expression.Conclusion:Long-term nebulization of non-nebulizer drugs can lead to pathological changes of lung tissue in SD rats,and the severity of respiratory tract injury varies with specific drugs.