The Effects Of Taurochenodeoxycholic Acid In Preventing Pulmonary Fibrosis In Mice

Pulmonary fibrosis is the most common diagnosis among patients presenting withinterstitial lung disease and one of the most serious diseases in respiratory system. It ischaracterized by diffusive alveolitis, structural disturbance in pulmonary alveoli and finallypulmonary interstitial fibrosis. However, treatment options for pulmonary fibrosis are verylimited. There is no evidence that any medications can help this condition.Taurochenodeoxycholic acid is present in the animal in the bile of a white powder, odorless,bitter taste of conjugated bile acids. Investigations on bile acid and its active ingredientshave appealed intensive attention. Since the discovery of the two receptors for bile acidFXRα (Kawamata et al.,2003) and TGR5(Hylemon et al.,2009) in1999and2003, bile acidhas been considered as a signaling molecule or a kind of hormone (Keitel et al.,2008),which play important roles in secretory regulation(Katsuma et al.,2005; Watanabe et al.,2006), energetic metabolism (Huang et al.,2006), liver regeneration promotion (Fiorucci etal.,2005), fibrosis prevention and other aspects in organisms. In2005and2007and haveconfirmed that FXR alpha agonist GW4064and acid to promote liver fiber dissolutionoccurred fibrosis reversal. And can play a protective effect on kidney.Current investigationshave confirmed that expression of two kinds of bile acid receptors FXRα and TGR5simultaneously existed in the lung of human(Hylemon et al.,2009; Gharaee-Kermani et al.,2005). It has not been reported that whether it also has functions in preventing pulmonaryfibrosis. The present study found after tests that FXRα and TGR5were also simultaneouslydetected in the lung of mice and thus mice were used as the subjects for preparing thepulmonary fibrosis model. Investigations on the effects of TCDCA in preventing pulmonaryfibrosis in mice were carried out, which may provide the basis for developing TCDCA intothe drug for preventing pulmonary fibrosis.In this paper, the bleomycin prepared the model of pulmonary fibrosis in mice (M.Gharaee-Kermani, et al,2005; M. Gharaee-Kermani, et al,2011), carried out TCDCAanti pulmonary fibrosis. In the experiment were randomly divided into five groups (n=16),respectively, for the normal group, model of pulmonary fibrosis group and high TCDCA oflow doses and dose group, dose, respectively0.05g/kg0.1/kg,0.2mg/kg. After the modelinggavage,1day, three weeks, the model group and blank group, normal saline. Experiment todetect the mouse lungs bile acid the receptor FXRα and the TGR5expression TCDCA,respectively, of pulmonary fibrosis in mice body weight, anatomy, lung coefficient,histopathology and TNF-alpha, MMP-2, MMP-9and TIMP-2expression.First test for detection of a bile acid receptor FXRα and TGR5expression in rats, mice,guinea pig organ. The results showed that TGR5in the various organs of rats, mice, guineapigs have a stable expression of the FXR only more content in the lungs of mice, expressionlevels in the rats rarely expressed in the guinea pig lung is not stability. Experimental design,mice were found in dose significantly increased the body weight of mice. Model group andthe high dose group after the autopsy serious lobe lesions, gray fibrinous exudate coverage.Visible on the lung surface and cut the majority of casual sex real change lesions, andpurulent secretions. Dose, and low-dose group, although some lesions, obvious changes inthe normal group. Have been improved compared with the model group. Lung coefficientresults showed that the lung coefficient of the model group and the high dose group wassignificantly increased in dose and low dose group improved, thus further evidence ofpathological change of lung. The test passed by HE and Masson staining of lung tissuebiopsy for further observation. It can be seen can be seen that the model group and the highdose group the alveoli filled with inflammatory exudate, and alveolar consolidation. Thealveolar space is filled with proliferated capillaries and fibroblasts, normal lung tissuestructure disappeared. High dose group in the part of the alveolar space consolidationprocess is accompanied by compensatory emphysema of the surrounding alveolar spaces.While the middle dose group and low dose group, although a small amount of inflammatoryexudate, but significantly reduced compared with the model group. Lung tissue structureand contours are still ringing in did not lose its function. Test by quantitative PCR techniqueon five indicators in the lungs of MMP-2and MMP-9, TIMP-2, and TNF-alpha. Found thatthe model group and normal group of TNF-α and of TIMP-2expression were significantly increase the expression of MMP-2and of MMP-9very significantly with lower; low-in,high three dosing group and model group phase comparison, all make very significant in themouse model of TNF-α, and TIMP-2decreased; low, compared to the two treatment groupwith the model group, both the mouse model of MMP-9significantly increased; the threetreatment group the MMP-2There was no significant impact. It appears, TCDCA toimprove the role of pulmonary fibrosis in mice.