重组腺病毒Ad-HGF抑制博来霉素致大鼠肺纤维化的作用

Inhibitory effect of Ad-HGF on pulmonary fibrosis induced by bleomycin in rats

目的:观察携带肝细胞生长因子基因的重组腺病毒(Ad-HGF)对博莱霉素(BLM)致大鼠肺纤维化的抑制作用,为基因防治肺纤维化探索有效途径.方法:BLM气管内滴注0.5mL(2mg)制作大鼠肺损伤模型60只,分为Ad-HGF治疗组(A组)、Ad-GFP治疗组(B组)和模型对照组(C组),各20只.造模次日A组给予1×109pfu Ad-HGF,B组给予1×109pfu Ad-GFP,C组给予0.5mL生理盐水灌注治疗;于14d处死动物,检测肺组织匀浆中羟脯氨酸含量;做石蜡切片,用1g/L苦味酸天狼猩红染色,偏振光显微镜观察胶原及其类型,并对切片中I型胶原进行半定量评估.结果:Ad-HGF组羟脯氨酸含量(1.91±0.16)mg/g较Ad-GFP组(3.27±0.43)mg/g和模型对照组(3.04±0.26)mg/g低(P<0.05);肺组织切片中的I型胶原Ad-HGF组(2.12±0.61)明显较Ad-GFP组(3.17±0.56)和模型对照组(3.38±0.66)稀少(P<0.05).结论:重组腺病毒Ad-HGF对肺损伤后纤维化有抑制作用.

AIM： To explore the effect of human hepatocyte growth factor （HGF） via a recombinant adenovirus mediated HGF gene （Ad-HGF） on bleomycin （BLM）-induced pulmonary fibrosis in rats. METHODS： Sixty Wistar rats in good conditions were intratracheally instilled with BLM 0.5 mL （2 mg）, and then randomly divided into 3 groups ： Ad-HGF treatment group （ group A）, Ad-GFP treatment group （group B） and model control group （group C）, 20 rats each group. On the 2nd day after intratracheal administration of BLM, A, B and C groups were intratracheally instilled with 1 ×10^9 pfu Ad-HGF, 1 ×10^9 pfu Ad-GFP and 0.5 mL normal saline, respectively. All rats were killed on day 14 after treatment. Collagen content of the lung tissue was assessed by hydroxyproline concentration. Distributions of collagen fiber 4 types in lung tissue of rats were observed and the degree of fibrosis was determined by semi-quantitative estimation of I type collagen fiber under polarizing microscope with stains of Sirius red. RESULTS ： The concentration of hydroxyproline in rat lung tissue from Ad-HGF treatment group [ （ 1.91 ± 0. 16） mg/ g] was significantly lower than that in Ad-GFP treatment group [ （3.27±0.43 ） mg/g ] and model control group [ （ 3. 04±0.26） mg/g, P 〈 0.05 ]. The sections stained with Sirius red showed type I collagen fiber was fewer in the Ad-HGF group （2.12 ± 0. 61 ）, while a huge amount of type I collagen was observed in the sections from Ad-GFP treatment （ 3.17 ± 0.56 ） and control group （3.38 ±0.66） ; there was significant difference between Ad-HGF group and Ad-GFP group or control group （ P 〈 0.05 ）. CONCLUSION： Ad-HGF can repress the formation of pulmonary fibrosis in rats.