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

Comparison of ω-3 fatty acids versus middle/light fatty acids in the intervention of rats model of bleomycin- induced pulmonary fibrosis

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1（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、10．534-4．21、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／m1]逐渐减低（P=0．044），IFN-γ含量[（5．67±0．13）、（6．58±0．64）、（7．05±0．52）pg／m1]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。

Objective To compare the effectiveness of ω-3 fatty acids and middle/light fatty acids in the intervention of rats model of bleomycin-indueed pulmonary fibrosis. Methods Totally 120 rats were randomly divided into 4 groups： normal saline （ NS ） group, bleomyein-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 21ts, day after modeling. The left lung were measured by using immunohistoehemical methods for transforming growth factor β1 （TGF-β1） and interferon garmma （IFN-＇,/）. The lower lobe of the right lung underwent HE stai- ning. Serum TGF-β1 , IFN-3,, 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 ex- pression 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-,t （ 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 7th, 14th, 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-~/levels [ （5.67 ± 0. 13 ）, （ 6. 58 ±0.64 ）, and （ 7.05 ± 0. 52 ） pg/ml ] were significantly higher （ P = 0. 048 ） on the 7th, 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.