The Influence Of Qidan Granule On The Expression Of Fasl,Caspase-3 In Bleomycin-Induced Pulmonary Fibrosis In Rats

Objective Lung fibrosis is a common feature of interstitial lung diseases, and apoptosis and fibrinogenesis play critical roles in its formation and progression.. Apoptosis of alveolar epithelial cells (AECs) has been implicated as a key event in the pathogenesis of lung fibrosis. The Fas/FasL pathway is a representative system of apoptosis-signaling receptor molecule systems. The caspase cascade is an executioner of apoptosis in several systems including the Fas/FasL pathway, caspase-3 plays a critical role. Qidan granule has been reported to decrease the extent of alveolitis and fibrosis. To investigate the influence of Qidan granule on the expression of FasL, caspase-3 in bleomycin A5-induced pulmonary fibrosis in rats and explore the mechanisms of Qidan granule on the proliferation of bronchial and alveolar epithelial cells (AECs). Methods 160 pathogen-free Sprague-Dawley(SD) rats were randomly divided into 6 groups(18 subgroups): normal control (control, 20 rats, 7-, 14-, 28- ,42-days subgroups), model (40 rats, 7-, 14-, 28- ,42-days subgroups), Qidan granule â… (30 rats, 7-, 14-, 28-days subgroups), Qidan granule â…¡(20 rats, 28- ,42-days subgroups), cortisol â… (30 rats, 7-, 14-, 28-days subgroups), cortisol â…¡(20 rats, 28- ,42-days subgroups). Male SD rats were intratracheally instilled with BLM. The controls were intratracheally instilled with saline. The animals were killed at 7, 14, 28, 42days after BLM instillation.. Microscopy was performed with HEperformed with antigen retrieval by heat using antibodies recognizing FasL and caspase-3 at 7,14,28 ,42days.Results Qidan granule decreased the exudation of inflammatory cell as well as the degree of fibrosis. There was no significant difference in the expression of FasL among all of 7d-subgroups. A statistically significant decrease in the expression of FasL was observed in Qidan granule I 14d-subgroup (PO.05) as compared with control. The difference among Qidan granule I 14d-subgroup and model n cortisol I was not significant. The expression of FasL of Qidan granule I 28d-subgroup was lower than those in model groups (all P<0.05). There was no significant difference between Qidan granule II and cortisol II groups(P>0.05).The expression of caspase-3 in Qidan granule 17d-subgroup was similar to those in cortisol and model groups . The difference between Qidan granule I 7d-subgroup and control was significant (PO.01). There was significant difference in the expression of caspase-3 between Qidan granule I 14d-subgroup and model group(PO.Ol). The difference among Qidan granule I 14d-subgroup and control > cortisol I was not significant. There was no significant difference in the expression of caspase-3 among Qidan granule I 28d-subgroup and cortisol I and control groups (all P>0.05). A statistically significant decrease in the expression of caspase-3 was observed in Qidan granule I 28d-subgroup as compared with controls (P<0.05). The difference between Qidan granule II 28d-subgroup and control was significant (PO.05). The expression of caspase-3 in Qidan granule II were similer to those in cortisol and model groups (P>0.05).FasL levels showed a positive correlation with caspase-3 levels (r=0.795, p<0.01) Conclusions Qidan granule can reduce the extent of alveolitis and fibrosis in BLM-induced pulmonary fibrosis in rats and repressing the expressions of FasL and caspase-3. Inducing apoptosis of alveolar epithelial cell may be one of the mechanisms.