| ObjectiveThe pathogenesis of pulmonary fibrosis is not clear at present.Although there are many western medicine treatments,they are not specific and lack specificity.A large number of clinical studies have shown that Chinese medicine can effectively alleviate various symptoms of pulmonary fibrosis.Based on the theory of "gold borns water" in Chinese medical theroy,there are many researches treating lung fibrosis from the view of kidney yang deficiency,but the exact mechanism of pharmacodynamics still needs further study.This paper intends to treat pulmonary fibrosis from kidney yang deficiency,we have the representative decoction of Youguiyin to cure pulmonary fibrosis in rats,to investigate the effect and the mechanism between lung and kidney,hoping to provide the basis for pulmonary fibrosis clinical treatment.MethodAs for the experimental study on the effect of kidney yang deficiency intervening pulmonary fibrosis in rats induced by hydrocortisone combined pulmonary fibrosis,15 rats of 10 week old male SD rats were randomly divided into normal group,model group,kidney yang deficiency&model group,with 5 rats in each group.The normal group without any intervention;the kidney yang deficiency&model group after 1 weeks of feeding were injected hydrocortisone(20mg/kg)into thigh muscles in the way of left and right crossover for 14 days to establish the model of kidney yang deficiency,then in fifteenth days,the kidney yang deficiency&model group and model group were both injected with bleomycin(5mg/kg)in trachea to establish the model of pulmonary fibrosis.On the 28th days of bleomycin induced rats,animal state,kidney yang deficiency indexes,lung quality,organ coefficient,lung function index,hydroxyproline content and HE staining and Masson staining were analysised,to evaluate the influence of hydrocortisone induced kidney yang deficiency on pulmonary fibrosis in rats.As for the study of the investigation of the efficacy of decoction of Youguiyin on pulmonary fibrosis in rats,25 rats of 10 week old male SD rats were randomly divided into five groups by the method of random number table,namely normal group,model group,the high,medium and low dose groups of Decoction of You Gui Yin,with 5 rats in each group.Without any intervention in the normal group,after a single intratracheal injections of bleomycin(5mg/kg)to establish pulmonary fibrosis model,rats were treated from 15th day daily with oral decoction of You Gui Yin of high,medium and low dose(20 g/kg?10 g/kg?5 g/kg)for 14 days.On the 28th day,to teste the animal pulmonary function and arterial blood gas,weighing weight of internal organs and body weight of rats,to detect the content of hydroxyproline in lung tissue and index of kidney yang deficiency in the serum,from the left lung HE and Masson staining to observe the pathological changes of lung tissue.In the study of the investigation of the mechanism of decoction of Youguiyin on pulmonary fibrosis in rats,renin,prostaglandin E2 and MMP-1 in the serum and the number of mononuclear cells in the blood were detected.The expression and distribution of a-SMA,COX-2,EP2,and EP3 in the lung tissue were observed via the immunohistochemical method.ResultsIn the experiment on the effect of kidney yang deficiency intervening pulmonary fibrosis in rats,the model group compared with normal group,pulmonary quality,lung index and 0.4 seconds(FEV0.4/FVC%)increased(P<0.05)and FVC decreased(P<0.05),hydroxyproline content decreased(P<0.05),the levels of PGE2 in the serum elevated(P<0.05),pathology revealed alveolar septal thicked and structural disordered,inflammatory infiltration of inflammatory cells can be seen,a large number of fibroblast proliferated and collagen deposited.The kidney yang deficiency&model group compared with model group,the quality of kidney,FVC,testosterone decreased(P<0.05),FEV0.4/FVC%,FVC/lung weight,the content of hydroxyproline and PGE2 showed no significant difference.Pathological examination showed that the degree of pulmonary fibrosis were slightly lighter than the model group.In the intervention experiment of Youguiyin on rats injected with pulmonary fibrosis,intratracheal injection of 5 mg/kg bleomycin can significantly increase the lung weight and lung coefficient(P<0.05),decrease Cdyn,FVC and FVC/lung weight(P<0.05),increase Ri(P<0.05),increase FEV0.4/FVC%(P<0.05),increase PCO2 in abdominal aortic blood(P<0.05),decrease PO2 and SO2 significantly(P<0.05).Pathology of lung tissue showed large area of consolidation in lung tissue of model rats,and those lung tissue was mostly formed by the non-fibrosis area with abnormal cell proliferation and fibrosis area with a large number of extracellular matrix deposition.Compared to the model group,the medium dose group of the decoction of You Gui Yin decreased the lung weight significantly(P<0.05),increased Cydn,FVC and FVC/lung(P<0.05),decreased Ri and FEV0.4/FVC%(P<0.05),while P02 and S02 of high dose group were significantly improved(P<0.05).Pathological examination showed You Gui Yin can inhibit chronic inflammatory infiltration from pulmonary consolidation to normally aerated lung parenchyma.In the mechanism exploring experiment of Youguiyin on rats injected with pulmonary fibrosis,compared with the normal group,PGE2 level in the serum in model group decreased(P<0.05),but there was no statistically significant difference in renin and MMP-1 levels,immunohistochemistry showed that the expression of a-SMA and COX-2 increased significantly.Compared with the model group,the level of PGE2 in the serum was increased(P<0.05),and the change in high dose group was the most obvious,and there was no statistical difference in the renin and MMP-1.The high dose group can significantly reduce the number of monocytes(P<0.05).Immunohistochemistry showed that as the dosage of You Gui Yin increased,the expression of COX-2 increased gradually,the number of fibroblasts expressing a-SMA in the fibrotic region decreased gradually,the number of EP2 positive endothelial cells in the real area decreased gradually and the number of EP3 positive monocytes in the transitional zone decreased gradually.Conclusion1.Hydrocortisone interfered with the rat model of bleomycin induced pulmonary fibrosis,which reduced the kidney quality and kindy coefficient,and accompanied the decrease of lung function,which may related to the dysfunction of the kidney.2.The decoction of Youguiyin could reduced the lung weight,improve the FVC,FVC/lung weight,Cdyn and blood gas of experimental pulmonary fibrosis rats,reduce the content of hydroxyproline and reduce the deposition of collagen,inhibit chronic inflammatory infiltration from pulmonary consolidation to normally aerated lung parenchyma,which showed Youguiyin was a favorable factor for the treatment of pulmonary fibrosis.3.The decoction of Youguiyin may increase the activity of COX-2 in the fibrotic regions and reduce the number of fibroblasts expressing a-SMA protein,which may be related to the reducing number of EP2 positive vascular endothelial cells promoting its rearrangement to participate in microvascular neovascularization and inhibiting the infiltration of EP3 receptors positive monocyte cells. |
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