| Objective:Pumlonary interstitial fibrosis is one of the most serious respiratory system disease, insidious onset. This disease can occur at any age grades, especially the people at the age of between 40 to 60. It is clinical feature appearance of dyspnea after activity, X-ray shows diffuse reticular and nodous shadow at both lungs. Pulmonary function test manifests that the patiens have restrictive ventilatory functional disturbance, diffusion functional disturbance and pulmonic compliance lose. Currently there are no proven effectiv ents. The median survival of patients is reported to be 2 to 5years after makeing a definite diagnosis. The pathogenesis of the disease are still unknown, maybe concerned with hereditary factor, smoking, contactting dust or metals, infection viral, chronic aspiration of tiny gastric contents repetatusly, dysimmunity, environmental pollution, drugs(such as Amiodarone and Bleomycin), and radial line. A great quantity studies confirm that cytokine has a key effect in the process of the generate and development of pumlonary interstitial fibrosis. Among the cytokine, TGF -β1, IGF-I, CTGF may be important in the process of the disease. This text established the mould of pumlonary interstitial fibrosis in rats through bleomycin. Observe the change of pulmonary pathology in curing bleomycin-induced pulmonary fibrosis. Measure the contents of hypdroxyproline(HYP) in the process of the disease. The expressing level of TGF -β1, IGF-I, CTGF in pulmonary tissue be determined by method of immunohistochemisty. Then explore its mechanisms through all of the methods.Methods:48 healthy male Sprague-Dawley(SD) rats(provided by Center Experiment Animal of Hebei Medical University) weighting 220±10g were randomly divided into two groups: physiological saline control group(group A) and Bleomycin group (group B), 24 in each group. And then each group were randomly divided into four groups by the four time periods(the 3thday, 7thday, 14thday, 28thday), which are 6 SD rats. Under the sterile conditions, the rats were anesthetized by injecting 10% hydral(3ml/kg) in abdominal cavity.And then cut open the cervical part, exposed the trachea fully. The animals were disembogued physic liquor slowly through injecting into interstice between the tracheal cartilages ring by 1ml syringe(group B: injecting 0.2～0.3ml BLMA5 solution , 5mg/Kg; group A: injecting 0.2～0.3ml physiological saline). Then made the animals straightening and revolving immediately, which made the physic liquor well-distributed in lungs. After establishing model, the animals were killed randomly at the 3thday, the 7thday, the 14thday, and the 28thday (n=6, at each time point) both the two groups. The animals were killed by the bloodletting method from bilateral femoral arteries and heart, middle lobes of right lung were made into tissue homogenate and were used for measureing the contents of HYP in pulmonary tissue. The inferior lobes of right lung were fixed in 4% paraformaldehyde, embedded in paraffin and sectioned. Estimate the degree of alveolitis and pulmonary fibrosis through hematoxylin-eosin(HE) staining and Masson staining. Alveolitis and pulmonary fibrosis were divided into 4 grades by the method of Szapiel. The expressing level of TGF -β1, IGF-I, CTGF in pulmonary tissue be determined by immunohistochemisty method in both model group and control group. Experimental data was done with SPSS13.0 statistical software.Results:1 Group B(Bleomycin group): The degree of alveolitis was all serious than that 28thday, which had statistical significance(P<0.01). Compared with group A, the degree of pulmonary fibrosis was no significant deviation at the 3thday, the 7thday(P>0.05), but there was significant deviation at the 14thday and the 28thday(P<0.01). The degree of pulmonary fibrosis was more serious than that of group A at that two time points. These indicate that the model of pulmonary fibrosis in rats established successfully by injecting BLMA5 into trachea and it is still a classical method now.2 The change of the content of HYP in lung tissue: The content of HYP of the group B shown an increase tendency accompany with the time. On the 3thday, It was higher a little than that of group A but there was no significant deviation (P>0.05). The content of HYP was significantly higher than that of the normal control group at the 7thday, the 14thday and the 28thday(P<0.05).3 The change of the content of TNF-αand TGF-β1,IGF-I,CTGF in lung tissue: The expression of TGF-β1,IGF-I and CTGF in group B was significantly higher than that in group A on the 3thday, the 7thday, the 14thday , the 28thday .There were statistical significance on each time point (P<0.05).Conclusions:1 Bleomycin-induced lung fibrosis in rat is successful,the model was simple in operation, higher in mission success rate, is a good model in research lung fibrosis.2 The change of the content of TNF-αand TGF-β1,IGF-I,CTGF in curing bleomycin-induced pulmonary fibrosis lung tissue: The expression of TGF-β1,IGF-I and CTGF in group B was significantly higher than that in group A on the 3thday, the 7thday, the 14thday , the 28thday .There were statistical significance on each time point (P<0.05).3 Linear correlation suggested that the pearson correlation between CTGF and TGF-β1 r=0.782, (p<0.01), the pearson correlation between IGF and TGF-β1 r=0. 8(p<0.01), suggested that the two factors are both have a correlation with TGF-1, They may have a synergistic action in the formation of pulmonary fibrosis. The inhibition of CTGFand IGF-1 may be more scientific and effective in pulmonary fibrosis treatment.4 The pearson correlation between CTGF and hyp r=0.804, (p<0.01),the pearson correlation between IGF-1 and hyp r=0.711,(p<0.01),the hyp is peculiar for collagen fiber, it can indirectly reflect the content of collagen, reflect the degree of fibrosis. It can come out that the expression of CTGF and IGF-1 in pulmonary fibrosis has a positive correlation with the degree in pulmonary fibrosis.
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