ABSTRACT
Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.
ABSTRACT
Objective To establish a zebrafish model of thrombosis induced by three kinds of inducers and observe the anti?thrombotic effect of a Chinese traditional medicine, Guanxinning tablet ( GXN) . Methods The zebrafish models of thrombosis was induced by using 1?5μmol/L phenyl hydrazine, 80μmol/L arachidonic acid and 5 mg/L ponatinib, re?spectively, and were treated with various concentration of GXN, clopidogrel or asprin. The thrombus in the tail vein was observed under microscope, Erythrocytes in the zebrafish heart were stained with o?dianisidine and the erythrocyte staining intensity was assessed with a NIS?Elements DTM image analyzer, and the anti?thrombolic effect of GXN was calculated. Results Venous thrombus was significantly increased and the staining intensities of erythrocytes in the heart were signifi?cantly decreased after induction by phenyl hydrazine, arachidonic acid or Ponatinib ( P <0?001 ) , respectively. At the same time, GXN showed an incresing anti?thrombolic effect in the zebrafish models (P<0?001) in a dose?effect manner, with a IC50 of GXN of 44?32 mg/L,138?5 mg/L and 459?5 mg/L, respectively. Conclusions The zebrafish models of thrombosis are successfully established by phenyl hydrazine, arachidonic acid or Ponatinib, respectively, by different for?mation mechanisms. GXN has been shown to have an anti?thrombosis effect, probably, by multiple target effects.