Inhibitory effect of pirfenidone on local fibrosis and HIF-1α expression in rat tracheal allografts

Abstract

Objective To study the influence of valsartan on local fibrosis and the expression of HIF-1α in rat tracheal allografts. Methods A rat heterotopic tracheal allograft model was established.The recipient rats were divided into three groups randomly: (1) Isograft control group: Both donors and recipients were SD rats and recipients were not treated; (2) Allograft control group: Donors were Wister rats, recipients were SD rats, and recipients were only administered with 0.5% carboxymethylcellulose and normal sodium by lavage after transplantation; (3) Allograft experimental group: Donors were Wister rats, recipients were SD rats, and recipients were administered with valsartan (60 plantation). On the day 28 after transplantation recipients were killed and tracheal grafts were harvested. Histologic and immunohistochemical examinations and in situ hybridization assay were performed. Results Obliterative bronchiolitis (OB)-like histologic changes in rat tracheal allografts were evident to varying degrees in two allograft groups. In allograft control group and allograft experimental group, the severity of local fibrosis was (65.94±17.05)% and (91.55±12.15)%, respectively;the expression index of col, col Ⅲ, HIF-1α, TGF-β and CTGF was 2.08±0.22 and 4.51±0.48,3.46±0.42 and 10.60±1.26, 7.62±0.59 and 9.34±0.62, 3.98±0.42 and 12.86±0.96, 6.65±0.52 and 11.83±0.96, respectively. In allograft experimental group, the expression col, col Ⅲ,HIF-1α,TGF-β and CTGF was reduced significantly. Conclusion Valsartan can inhibit the development of OB in the rat heterotopic tracheal allograft model by inhibiting HIF-1α. Key words: Bronchiolitis obliterans; Valsartan; HIF-1α; Tracheal transplantation