ω-3鱼油脂肪乳和中/长链脂肪乳注射液干预博莱霉素致肺纤维化大鼠效果的比较

摘要

Objective To compare the effectiveness of ω-3 fatty acids and middle/light fatty acids in the intervention of rats model of bleomycin-induced pulmonary fibrosis.Methods Totally 120 rats were randomly divided into 4 groups: normal saline (NS) group,bleomycin-induced pulmonary fibrosis without treatment group ( BLM group),middle/light fatty acids group,ω-3 fatty acids group.Lung tissues were obtained on the 7th,14th,and 21st day after modeling.The left lung were measured by using immunohistochemical methods for transforming growth factor β1 (TGF-β1) and interferon garmma ( IFN-γ).The lower lobe of the right lung underwent HE staining.Serum TGF-β1,IFN-γ,and interleukin-4 (IL-4) were measured using double-antibody sandwich ELISA.Results The pulmonary alveolitis and fibrosis in the ω-3 fatty acids group was significantly milder than in middle/light fatty acids group and BLM group.On the 7th,14th,and 21st day after modeling,stronger TGF-β1 protein expression was detected in the bronehiolar epithelia of middle/light fatty acids group and BLM group and poorer IFN-γexpression in both groups.However,the opposite results were found in the ω-3 fatty acids group: on the 7th,14th,and 21st day after modeling,TGF-β1 protein expression ( 13.60 ± 5.90,10.53 ± 4.21,and 7.23 ± 2.21 )was lower ( P =0.047) and IFN-γ ( 13.85 ± 7.48,15.32 ± 2.12,and 18.74 ± 2.65 ) was stronger in ω-3 fatty acids group (P =0.041).On the 7 ,14,and 21st day after modeling,the serum IL-4 levels in the middle/light fatty acids group and BLM group became significantly higher,while the IFN-γ level in both groups was significantly lower than in ω-3 fatty acids group ( P =0.008 ) ; meanwhile,in the ω-3 fatty acids group,the serum IL-4 levels [ (8.73 ± 1.20),(5.73 ±2.03),and (4.98 ± 1.89) pg/ml] were significantly lower (P =0.044) and serum IFN-γlevels [ (5.67 ± 0.13 ),( 6.58 ± 0.64 ),and ( 7.05 ± 0.52 ) pg/ml ] were significantly higher ( P =0.048 ) on the 72,14th,and 21st day after modeling.Conclusions ω-3 fatty acids can lower TGF-β1 protein expression in rat lung tissue and reduce the surum TGF-β1 and IL-4 levels.Compared with the middle/light fatty acids,it can more effectively upregulate the expression of IFN-γ in lung tissue and increase its serum level,and thus alleviate pulmonary fibrosis in rats.%目的 探讨ω-3鱼油脂肪乳和20％中/长链脂肪乳注射液干预博莱霉素致肺纤维化大鼠的不同效果.方法 将清洁级雄性大鼠120只,完全随机分成生理盐水正常组、博莱霉素致大鼠肺纤维化模型对照组、博莱霉素致大鼠肺纤维化+20％中/长链脂肪乳注射液(LCT组)和博莱霉素致大鼠肺纤维化+ ω-3鱼油脂肪乳(ω-3PUFA组).在第7、14、21天分别取左肺下叶进行免疫组织化学检测转化生长因子β1(TGF-β1)和干扰素γ(IFN-γ)的表达,右肺下叶进行HE染色病理观察；采用ELISA双抗体夹心法测定各组大鼠血清白细胞介素4 (IL-4)和IFN-γ的含量.结果 ω-3PUFA组大鼠肺泡炎、肺纤维化程度较对照组和LCT组轻；对照组和LCT组大鼠在第7、14、21天的肺组织TGF-β1染色呈强阳性,IFN-γ染色较淡,而ω-3PUFA组TGF-β1和IFN-γ染色则相反,第7、14、21天,TGF-β1定量表达( 13.60±5.90、10.53±4.21、7.23±2.21)逐渐减少(P=0.047),IFN-γ定量表达(13.85 ±7.48、15.32 ±2.12、18.74±2.65)逐渐增加(P=0.041).对照组和LCT组大鼠第7、14、21天血清IL-4含量较高,IFN-γ含量较低；而ω-3PUFA组则相反(P =0.008),ω-3PUFA组第7、14、21天IL-4含量[(8.73±1.20)、(5.73±2.03)、(4.98±1.89) pg/ml]逐渐减低(P=0.044),IFN-γ含量[(5.67±0.13)、(6.58±0.64)、(7.05±0.52) pg/ml]逐渐增加(P=0.048).结论 ω-3鱼油脂肪乳可以下调大鼠肺组织TGF-β1,降低其血清含量和IL-4含量；上调肺组织IFN-γ的表达,增加其血清含量,在小动物中减轻肺纤维化优于中/长链脂肪乳注射液.