Study On The Effective Mechanism Of Compound Decoction Of Strengthening The Spleen And Dredging Collaterals In Pulmonary Interstitial Fibrosis Rats

ObjectiveAccording to the study on the pathogenesis and developing process of pulmonary interstitial fibrosis (PIF) and the observation of its clinical presentations, in combination of the study on the literatures of both present and the past, we put forth that "deficiency in the root and excess in the branch", "the spleen insufficiency and collateral stasis" are the principle of the pathogenesis of the disease. In the clinical practice, we have been used Compound Decoction of Strengthening the Spleen and Dredging Collaterals (CSSDC), with some modifications based on the principle of "Treatment Differentiation Based on Syndrome Differentiation" as the whole, and we have got satisfactory results in prevention and treatment of PIF. In this study the effect of CSSDC on the activity of nuclear factor (κB), the gene expressions of tumor necrosis factor alpha (TNF-α) and platelet-derived growth factor (PDGF) and the protein levels in pulmonary tissues of rats with experimental PIF have been studied at the molecular biology level, in order to explore its mechanism in treatment of pulmonary interstitial fibrosis so as to provide an effective remedy for it clinically.MethodRats were divided into 4 groups: normal control group, model group, Chinese Medicine treatment group and Western Medicine control group. The rats in the last three groups were by garage given Bleomycin A5 5mg/kg for establishment of IPF models. Then the rats in the Chinese Medicine group were treated with CSSDC and those in the Western Medicine control group were given hydrocortisone for consecutive four weeks. At the ends of 1st, 2nd, 4th week treatment, the samples chosen from the upper right lungs of the rates in the 4 groups were respectively taken for HE stain and Masson stain to investigate their degrees of alveolitis and pulmonary fibrosis. And the activity of NF-κB, the expressions of both TNF-αmRNA and PDGF in cells of lung tsissues detected by immmunohistochemistry, the protein levels of NF-κBmRNA, PDGFmRNA in cells of lung tsissues were also detected by RT-PCR.ResultsPathological result showed that pathological changes of alveolitis and fibrosis of the rats in both the Chinese Medicine treatment and the Western Medicine control group were milder more obviously than those in the model group at the end of 1st, 2nd, 4th week; but there was no significant difference between the two treatment groups. Compared with the normal control group, at the end of 1st week, the activity of NF-κB, and the expressions of TNF-αmRNA and PDGFmRNA of pulmonary tissue all increased in the model group, and the values of the Chinese Medicine treatment group and the Western Medicine control group were lower than those of the meddle group (P_NF-κB＜0.05, P_TNF-α＜0.01, P_PDGF＜0.01). The values in the Chinese Medicine treatment group were obviously lower than those in the Chinese Medicine control group, but with no statistical significance. At the end of 2nd week, the activity of NF-κB dropped to the normal level. However the expressions of TNF-αand PDGF were still higher than the normal, but lower than what they were at the end of 1st week. In normal pulmonary tissue of the rats there was no expression of TNF-αand PDGF, while in pulmonary fibrosis tissue of the rats there were expressions of them and the expressions could remain for 28 days.Conclusion1. The CSSDC can improve the pathological changes of alveolitis and fibrous degeneration of the rat models with pulmonary interstitial fibrosis.2. The CSSDC can restrain the activities of NF-κB, TNF-αand PDGF of pulmonary tissue of the rat models with pulmonary interstitial fibrosis. 3. The CSSDC can decrease the expressions of NF-κB mRNA and PDGF mRNA of pulmonary tissue of the rat models with Pulmonary interstitial fibrosis.4. The therapeutic effect of CSSDC is better than that of Western medicine.5. The CSSDC can improve the inflammation and fibrous degeneration by means of inhibiting the activities of NF-κB, TNF-αand PDGF, and reducing the expressions of NF-κB mRNA and PDGF mRNA, which is one of the mechanisms for treatment of pulmonary interstitial fibrosis.