Probing into the Mechanism of Alkaline Citrus Extract Promoted Apoptosis in Pulmonary Fibroblasts of Bleomycin-Induced Pulmonary Fibrosis Mice

Received Oct 19, 2017; Revised Feb 7, 2018; Accepted Feb 18, 2018

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1. Introduction

Pulmonary fibrosis is a chronic diffusive interstitial lung disease [1]. The primary pathological feature is extracellular matrix deposition (ECM) that may cause abnormal remolding of pulmonary tissues, respiratory failure, and even death eventually [2]. It is now universally acknowledged that pulmonary fibroblast is the core step of pulmonary fibrosis and that effective intervention of the biological behavior of pulmonary fibroblasts can prevent and cure pulmonary fibrosis. Pulmonary fibroblasts proliferate and differentiate into myofibroblasts when pulmonary tissues were damaged, express specially alpha smooth muscle actin ($\alpha$-SMA), overproduce ECM, and speed up the process of pulmonary fibrosis [3]. Therefore, removal of activated pulmonary fibroblasts and reduction of the secretion and deposition of ECM are effective tactics for the treatment of pulmonary fibrosis.

Currently, it is believed that accelerated pulmonary fibroblast apoptosis is a critical step for controlling the occurrence and development of pulmonary fibroblasts [4]. Domestically and internationally, a majority of researches concerning the control of pulmonary fibroblast activity concentrated on the inhibition of pulmonary fibroblast proliferation and collagen secretion. Although evolution of pulmonary fibrosis can be alleviated to a certain degree by this method, it is very difficult to completely inhibit its proliferation because of its high productivity [5]. Inhibition of collagen synthesis does not reduce the quantity of pulmonary fibroblasts and therefore cannot radically clear off pulmonary fibroblasts. The pulmonary fibroblast itself not only has strong antiapoptosis capacity, but also can induce the apoptosis of pulmonary epithelial cells and accelerate the evolution of pulmonary fibrosis [6]. Therefore, effective acceleration of pulmonary fibroblast apoptosis is of very important significance for the treatment of pulmonary fibrosis.

It has been confirmed that Fas-induced apoptosis signaling pathway plays a crucial role in pulmonary fibrosis [7]. Fas binds to FasL to form a death-induced compound. This compound activates Caspase 8 that induces Caspase 3 production and activates death receptor apoptosis pathway [8]. At present, it is believed that COX-2 plays an important role in regulating the expression of Fas receptor in pulmonary fibroblasts [9]....