摘要
目的观察吡啡尼酮对大鼠异位气管移植物局部纤维化和气道闭塞的抑制作用及其对缺氧诱导因子(HIF)-1α表达的影响。方法建立大鼠同种异体异位气管移植模型,受体鼠随机分为同基因移植组、异基因移植未治疗组和吡啡尼酮组,吡啡尼酮组给予吡啡尼酮(每日600 mg/kg体重);其他组不给任何药物。移植后第28天处死受体鼠并取出移植物进行病理学、免疫组织化学及原位杂交检测。结果未处理组气管移植物可观察到各种程度类似于闭塞性细支气管炎(OB)的病理改变。与未处理组比较,吡啡尼酮组标本局部纤维化程度[(42.45±19.09)%比(91.55±12.15)%]及Ⅰ型胶原1.86±0.12比4.51±0.48、Ⅲ型胶原2.55±0.37比10.60±1.26、HIF-1α4.48±0.43比9.34±0.62、转化生长因子(TGF)-β5.00±0.49比12.86±0.96和结缔组织生长因子(CTGF)4.33±0.64比11.83±0.96的表达明显受到抑制(P<0.01)。结论吡啡尼酮在大鼠异位气管移植模型中可能通过抑制HIF-1α的表达而抑制了OB的进展。
Objective To study the influence of pirfenidone on local fibrosis and the expression of HIF-1 α in mouse tracheal allografts. Methods A murine heterotopie tracheal allograft model was established. The recipient mice were randomly divided into three groups （n = 12 in each） ：isograft group;allograft untreated group;allograft pirfenidone （600 mg/kg every day）-treated group. Pathological examination,immunohistoehemistry and in situ hybridization were performed on the tracheal grafts at 28th day after transplantation in the sacrificed recipient mice. Results OB-like histologie changes to varying degrees in mouse tracheal allografts of untreated groups were observed. In contrast with allograft untreated group, the degree of local fibrosis [ （42.45 ± 19.09 ） % vs （ 91.55 ± 12.15 ） % ], the expression of colⅠ（ 1.86 ± 0.12 vs 4.51 ± 0.48 ）, colⅢ （2.55 ± 0.37 vs 10.60 ± 1.26 ）, HIF-α （ 4.48 ±0.43 vs 9.34 ± 0.62 ）, TGF-β （5.00 ± 0.49 vs 12.86 ± 0.96） and CTGF （4.33 ± 0.64 vs 11.83 ± 0.96 ） in pirfenitone group were decreased significantly. Conclusion Pirfenidone may inhibit the development of the OB-like lesion in murine heterotopie tracheal allograft model by inhibiting the expression of HIF-1 α.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2007年第9期1099-1101,共3页
Chinese Journal of Experimental Surgery
