The Effect Of Loratadine On Expression Of Interleukin 5 And Eosinophil Apoptosis In Asthmatic Guinea Pigs

Objective: To observe whether the airway hyperresponsiveness, concentration of IL-5 and the count of EOS in blood and BALF, delayed apoptosis of EOS were influenced in asthmatic modle of guinea pigs after feeding Loratadine. Exploring the potential therapeutical value of H1 receptor antagonist and Searching new therapeutical target for asthma treatment. Methods : 32 guinea pigs were divided into normal control group , asthmatic group,low dose and high dose group of Loratadine. After animal modle is accomplished,feeding Loratadine 2mg/kg,10mg/kg respectively.Mensurating the airway pressure by the animal respirator.Euzymelinked immunosorbent assay is used to measure the IL-5 in BALF and peripheral blood,meanwhile, eosinophil count is also detected.Lung tissue were purfused by paraformldehyde in order to be fixed.In situ cell death detection kit(POD) was used to detect the apoptosised EOS in the lung tissue.Results: (1).When the concentration of histamine phosphate is 10mg/l,the airway pressure in normal control group,asthmatic group,low dose and high dose group of Loratadine are(2.3±0.2)Kp,(3.2±0.2)Kp,(3.0±0.1)Kp,(2.8±0.2) Kp;When the concentration of histamine phosphate is 20mg/l,the airway pressure about these groups are (2.4±0.2)Kp, (4.2±0.2)Kp, (3.8±0.2)Kp, (3.5±0.1)Kp.(2).The serumal IL-5 in each groups are (0.27±0.04)ng/l, (0.41±0.03)ng/l, (0.38±0.02)ng/l, (0.31±0.03)ng/l;IL-5 in BALF are respectively(0.1±0.01)ng/l, (0.38±0.04)ng/l, (0.33±0.05)ng/l, (0.23±0.09)ng/l;(3).The count of EOS in serum are(4.0±0.6)×10~8/L, (54.6±7.6)×10~8/L, (44.5±3.9)×10~8/L, (29.0±5.8)×10~8/L;EOS in BALF in each groups are(3.0±0.5)×10~8/L, (33.7±3.9)×10~8/L,(27.1±3.2)×10~8/L,(18.6±3.3)×10~8/L. (4). The apoptosised cells in the four groups are 33,95,129,182 in 1600 cells.The difference only between the asthmaic and the low dose group of Loratadine in EOS apoptosis index and airway pressure when the concentration of histamine is 10mg/ml is not significan(tP>0.0083,P>0.05),the comparison between every two groups in other measurements the differences are significant(P<0.05).Conclusions: (1).Through antiapoptosis signal transduction pathway,IL-5 induce delayed apoptosis about EOS.The transmigration and exudation of EOS into the airway and lung tissue are increasing,keeping and aggrevating the pathological changes,this could be one of the mechamisms about the anaphylactic inflammation in asthma.(2).Loratadine which is the second generation of H1 receptor antagonist expedite the apoptosis of eosinophil directly or indirectly,through restrainting the antiapoptosis signal transduction pathway,relieve the persistent state of eosinophil inflammatiom would be the mechanism of Loratadine acting on the anaphylactic inflammation in asthma. (3).Besides the simplex effect of antianaphylaxis,Loratadine could reverse the IL-5 afforded delayed apoptosis,ameliorate the inflamatory state in lung tissue,offer the potential active therapeutical value in asthma management.