Effect Of Thalidomide On Expression Of ICAM-1、TGF-β₁in Pulmonary Fibrosis In Rats

Objective：Pulmonary fibrosis is refers to the unknown cause and thecommon interstitial pneumonia (UIP) as the characteristic pathologicalchanges of a chronic inflammatory interstitial lung disease, idiopathicinterstitial pneumonia is the most common type.So far no effective therapeuticdrug.the median survival time less than3years.In X-ray chest radiographchanges the floorboard of the heterogeneous disease, and lung functiondamage with diffuse alveolar inflammation and inflammation of the lungparenchyma and interstitial fibrosis pathological features. Idiopathicpulmonary fibrosis (IPF) means that for unknown reasons and, in ordinaryinterstitial pneumonia (UIP) as the characteristic pathological changes of achronic inflammatory interstitial lung disease, main show is diffuse alveolarinflammation, alveolar unit structure disorder and pulmonary fibrosis.Causeof pulmonary fibrosis, pulmonary injury factors is not clear,some people thinkthat with genetic susceptibility, viral infections, immune dysfunction and so on.All kinds of damage factors damage alveolar epithelial cells and capillaryendothelial cells, cause alveolar macrophages(AM)activation,monocy-tes,neutrophils, lymphoc-ytes and eosinophils inflammatory cells infiltrationand inflammatory cells and the release of cytokine and inflammation factormediating the early lung injury. Pulmonary interstitial fibrosis traditionaltreatments include: adrenal glucocorticoid hormones (hormone) therapy,immune inhibitors and anti fibrosis agents alone or associated with hormonetherapy.Thalidomide as a sedative and analgesic in early, and later found tohave immunomodulatory and anti-inflammatory effects.In90s,somebodyfound that thalidomide could be examined adjustment TNF-α levels,reduceTNF-α,IL-6and IL-10mRNA levels, thus inhibiting the process of pulmonaryfibrosis. This experiment was to study the effects of thalidomide on bleomycin-induced pulmonary fibrosis in rat.By measuring the serum ICAM-1,TGF-β1expression levels to explore the possible mechanism of action.Method: select clean and healthy, male SD rats (provided byexperimental animal center of Hebei Medical University)72,weight250-300g,adaptability to raise (time) for one week, Then randomly divided into fourgroup:(1) normal control group (group A):18rats, and0.9%Nacl solutionaccording to0.1ml/100g injection method into the trachea, and0.9%Naclsolution in accordance with the method of1ml/100g lavage (time starts from1days after forging die),1time/day,and in7days,14days,28daysrespectively each executed6;(2)the model group (B group of bleomycingroup):18rats,a one-time use syringe to bleomycin A5(5mg/kg) evenly intothe trachea, and0.9%Nacl solution1ml/100g lavage(time starting from themold after the first day),1times/day, in7days,14days,28.executed6rats.(3) the intervention group (C group):18rats made, the bleomycin A5(5mg/kg) uniform with a syringe, disposable injection into the trachea, andwithin1day after the model caused by amine solution with1%of thalidomide,(thalidomide with0.9%Nacl solution in proportion according to100mg/kg) inproportion according to the100mg/kg of methods to fill the stomach,1time/day, respectively, in7days,14days,28days are executed only6;(4) thedexamethasone group, the intervention group (D group):18rats, thebleomycin A5(5mg/kg), one-time evenly to the endotracheal injection, and1day after the model from the start will dexamethasone according to0.3mg/100g/d method of intraperitoneal injection, respectively, in7days,14days,28days each executed six only. Each separate bilateral femoral artery,payattention to try to reduce the stimulation of femoral artery, the femoral arteryafter free,with scissors cut the bilateral femoral artery, the blood put net,ratswere executed at the same time.Take the right lung lobe fixed in4%paraformaldehyde solution.using immunohistochemical method to detectICAM-1,and TGF-β1and image analysis system, measure and record eachview positive staining of the average positive cell counts and the average optical density (IOD) values.With HE staining and Masson staining methodfor each group of rats alveolar inflammation and fibrosis of lung tissue toevaluate the development degree and classification according to Szapielmethod at the same time, can be divided into category4. Using SPSS13.0statistical software for each set of data for analysis.Results:1pulmonary histopathologic analysis results:At the same time, group Balveolitis were significantly higher than that of A group (P<0.05), group Bpulmonary fibrosis were significantly higher than that of A group,on7days(P>0.05),14days,28days (P<0.05), show that replication of an animal modelof success.Thalidomide groups alveolitis degree:7days,14days thalidomidegroup alveolitis significantly reduced compared with the bleomycin group（P<0.05）,On28days control group and model group alveolitis have nodifference（P>0.05）.Fibrosis degree:7days normal control group and modelgroup have no difference（P>0.05），14days and28days, the two groupscompared with the normal control group is seriou（sP<0.05）.14days (P>0.05),no difference with the model group. At28days fibrosis compared with themodel group reduced(P <0.05).Dexamethasone group alveolitis，7days14days compared with normal control group seriously，compared with the modelgroup light（P<0.05）.On28days with normal control group and model groupare undifferentiated（P>0.05）.Fibrosis degree:7days no difference comparedto the normal control group and model group（P>0.05），14days is heavierthan the degree of the control group（P<0.05）.No difference compared withthe model group（P>0.05），28days compared with the control group, nodifference（P>0.05）.Compared with the model group relief（P<0.05），On thesame time, dexamethasone and thalidomide group alveolitis and fibrosis werenot statistically significant（P＞0.05）.2lung tissue collagen content change (IOD): group B in rat lung tissuecollagen content with the molding time gradually increased,28days up to themaximum value,7days,14days,28days compared with the control groupwas statistically significant(P<0.05); C group, D rats of type Ⅲcollagen content was low level increased, Content were lower compared with the modelgroup(P<0.05); but in C group, D group showed no significant difference (P>0.05).14days,28days thalidomide group Ⅲcollagen contentthandexamethasone group low, with statistical significance（P<0.05）.3Changes in contents of ICAM-1, TGF-β1in serumThe serum TGF-β1model of rats in the groups were significantly higherthan the other three groups,The difference was statistically significant，（P<0.05）Dexamethasone and thalidomide group compared with statisticalsignificance have Statistical significance on7day and14day（P<0.05）.Notstatistically significant in28days（P＞0.05）.The ICAM-1content in serum of the rats in the model group increasedgradually,to28days to reach the maximum value.At the same time pointswere higher than those in normal control group,Dexa methasone andthalidomide group.In7days,14days and the other three groups showedsignificant difference（P<0.05）.Not statistically significant in28days（P＞0.05）.Conclusions:1In bleomycin induced pulmonary fibrosis in rats model,thalidomide canbe reduced pulmonary interstitial collagen deposition, to have a therapeuticeffect of pulmonary fibrosis.2In bleomycin induced pulmonary fibrosis in rats model,thalidomideand dexamethasone have similar anti fibrosis effect. its mechanism may bethrough inhibiting cytokines expression of ICAM-1and TGF beta1, so asto reduce the early inflammatory response and blood vessel formation,eventually inhibition process of pulmonary fibrosis.