Experimental Study And Clinical Experience On Treatment Of Idiopathic Pulmonary Fibrosis With

ObjectiveSummary the theory of my tutor’s treatment of pulmonary fibrosis,and the clinical experience of treating this disease with Bushenyifeixiaozheng decoction.Establish the pulmonary fibrosis rats model,to investigate the influence of Bushenyifeixiaozheng decoction on changes of lung tissue pathology and ultrastructure and to explore the mechanism of Bushenyifeixiaozheng decoction on genes and protein expression of Caspase-12 signaling pathway, including GRP78、Caspase-12、CaMKⅡ、 GADD153.Methods1.Sorting my tutor’s related medical cases,discuss on the theoretical origin of "micro abdominal mass in lung collaterals",the treatment principle of "three phase partition",and clinical experience.2.Sixty SD rats were randomly divided into 6 groups:normal group、model group、 pirfenidone group、preventing group、treatment group、control(preventing and treatment) group.Except normal group,others were instilled with bleomycin through tracheal intubation. After 24 hours the rats were given drugs respectively by intragastric administration. Preventing group and control group were given Bufeiyishenxiaozheng decoction while others were given normal saline.Preventing group was killed at 28th day to observe the effecs of preventive drug delivery in IPFAt the same time,pirfenidone group and treatment group were respectively given pirfenidone and Bufeiyishenxiaozheng decoction.All groups were killed at 56th day.HE and Masson staining were performed to investigate pathological changes and fibrosis.Electron microscopy to observe its ultrastructure.The related protein and genes expression of Caspase-12 apoptosis pathway in lung of IPF were detected by Western blot and Real-time PCR.Results1.The result of HE stain analysis in lung tissue showed that in model group alveolar structure was destroyed,inflammatory cells appeared,and alveolar walls were thicken. Pirfenidone group and Chinese medicine groups showed part of structure changed,the degree of pulmonary fibrosis is lighter Masson stain revealed that compared with model group collagenous fiber was less in the pirfenidone group and Chinese medicine groups.Electron microscopic findings were:in model group,the structures were incomplete.collagen deposition existed,basement membrane was thicken,and endoplasmic reticulums were expanded. Pirfenidone group showed a much better situation,collagen deposition and electron density were less.In preventing group and treatment group,basement membrane was thicken lightly, endoplasmic reticulums expanded mildly.Control group was the best,collagen deposition was least and hardly saw the expansion of endoplasmic reticulums.2.The related genes expression of Caspase-12 pathway(including GRP78、Caspase-12、 CaMKⅡ、GADD153) were significantly high in model group compared with normal group(P<0.05).In pirfenidone group GRP78 and CaMK II expressed less(P<0.05).There was no significant difference in preventing group,but it could still be seen the decline trend. In treatment group Caspase-12、CaMK II and GADD153 expressed less(P<0.05).In control group GRP78、Caspase、CaMKⅡ and GADD153 expressed less(P<0.05 or P<0.01).3.The related protein of Caspase-12 pathway (including GRP78、Caspase-12、CaMK Ⅱ、 GADD153)was highest in model group(P<0.05).In pirfenidone group GRP78 and Caspase-12 expressed lower(P<0.05).In preventing group GRP78 expressed lower(P<0.05),other proteins showed no significant difference but a decline trend.In treatment group GRP78、Caspase-12、 CaMK Ⅱ、GADD153 expressed lower(P<0.05).In control group GRP78、Caspase-12、 GADD153 expressed lower(P<0.05 or P<0.01).Conclusion1.Tutor thinks IPF is because of pulmonary collateral impairment,abdominal mass is the pathological product of collateral disease,with the development of the disease finally become "micro abdominal mass in lung collaterals". According to different stages of the disease,tutor proposes "triple-stage treatment",invigorating lung and kidney while eliminating pathogen, creating Bufeiyishenxiaozheng decoction based on Jinshuiliujun decoction.Applying this decoctiong in the clinic can effectively improve the symptoms of patients,improve their life and treatment,enhance the patients’ resistance to reduce the recurrent disease,so as to slow down the disease process.2.This decoction may regulate endoplasmic reticulum stress,reduce alveolar epithelial cell apoptosis,improve the degree of pulmonary alveolar inflammation and fibrosis,so as to inhibit the process of pulmonary fibrosis.3.This decoction can control the expression of caspase-12 pathway genes and proteins in lung tissues,thereby reducing alveolar epithelial cells endoplasmic reticulum stress,delay and inhibit idiopatbic pulmonary fibrosis process of change, to achieve the purpose of treatment.