| Background:Asthma is an allergic disease,one common disease in chronic illness of respiratory system.Its airway is characteristed by hyperreactivity,chronic inflammation and remodeling.With the development of society,the incidence of asthma upgrades,especially in the children,which brings extended burden and pressure to society and family.The pathogenesis and treatment of asthma are investigative hotspots constantly.Furthermore, realization of asthma in the molecule-gene level has already begun.However, many inflammatory cells and cytokines are correlated with asthma.No current treatment can reduce or prevent asthma in a long period.Further study on pathogenesy of new interference target of asthma has been generally investigated in medical science.Objective:To observe the expression of TIMP-1(tissue inhibitor of metalloproteinase-1) in the lung tissue on the airway remodeling in the rats of the asthmatic model.Measure the airway smooth muscle area and the inner wall area standardized by the basement membrane perimeter with software of computer image analysis in the asthmatic rats model.Quantify the level of the airway remodeling with the smooth muscle area and the inner wall area of the airway.Study the effects of anti-RANTES (regulated on activation normal T cell expressed and secreted) antibody on the airway remodeling,and the new way of prevention of asthma was offered.Method:The rats were randomly divided into three groups:asthmatic model group,anti-RANTES antibody intervention group and normal control group,each group had 12 rats.The rats of asthmatic model group and anti- RANTES antibody intervention group were immunized by intraperitoneal injection of 10% ovalbumin on the first,the seventh and the fourteenth day of the study.The rats of normal control group were given equivalent physiological saline to allergize.From the third weeks,the rats of asthmatic model group and anti-RANTES antibody intervention group were stimulated by aerosol inhalation of 1% ovalbumin (OVA),once of two days,thirty minutes every time,which were repeated six weeks.The rats of normal control group received stimulation with inhalation of physiological saline.From the fourth weeks,the rats of anti-RANTES antibody intervention group were intervened by caudal vein injection of anti-RANTES antibody,one microgramme every time before each stimulation, which were repeated five weeks.The rats of asthmatic model group and the rats of normal control group were caudal vein injection of equivalent physiological saline.To observe the behavior change of the three groups,including the action,the respiration,the appearance and the hairs of rats.The rats were anesthetized with l% pentobarbital when the end of the last stimulation.Pathological slides were prepared from left lung and stained with hematoxylin-eosin.The airway smooth muscle area (WAM),and the inner wall area (WAi) of the airway were measured and standardized by the basement membrane perimeter (Pbm). Expression of tissue inhibitor of metalloproteinase-1 were detected by immunohistochemistry.Results:When the rats were stimulated in the asthmatic model group, they showed restlessness,scratching honor,sneezing,nose fanning,mouth breathing deepenly and quickenly,oral lip cyanochroia,and all the show above- mentioned releasing gradually after the inhalation.The HE stained section of the asthmatic model group showed mucosal edema,air duct thickening,plica to grow in number.Compared with the asthmatic model group,there were mild symptom and inflammation reaction,and decrease in air duct thicken in the anti-RANTES antibody intervention group.The rats of the normal control group showed normal diet and drinking,animation,sensitiveness,breathing stable.The airway smooth muscle area and the inner wall area of the asthmatic model group [WAm/Pbm(5.78±1.36)μm2/μm,WAi/Pbm(15.10±3.99)μm2/μm] was greater than the normal control group[WAm/Pbm(3.35±1.01)μm2/μm, WAi/Pbm(9.25±2.29)μm2/μm](all P<0.05).The airway smooth muscle area and the inner wall area of the anti-RANTES antibody intervention group [WAm/Pbm(4.12±1.21)μm2/μm,WAi/Pbm(10.01±2.69)μm2/μm]was greater than asthmatic model group (all P<0.05),but no statistical significance compared to the normal control group (all P>0.05).The relative integral optical density value of the tissue inhibitor of metalloproteinase-1 in the lung tissues was increased significantly in the asthmatic model group [1.9580±0.0927] than the normal control group [0.7623±0.1000](P<0.05).The relative integral optical density value of the tissue inhibitor of metalloproteinase-1 in the lung tissues in the anti-RANTES antibody intervention group [0.9770±0.0233] was decreased significantly than the asthmatic model group (P<0.05),but no statistical significance compared to the normal control group (P>0.05).Conclusion:The asthmatic rats model were succeeded.The tissue inhibitor of metalloproteinase-1 had relationship with asthma airway remodeling.The anti-RANTES monoclonal antibody leads to decrease of the expression of the tissue inhibitor of metalloproteinase -1 in the lung tissue of asthma rats,lessen asthma attack,inhibit the airway inflammation,delay development of airway reconstitution.The anti-RANTES antibody takes an important role in delaying development of asthma airway remodeling. |
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