ω-3多不饱和脂肪酸对肥胖小鼠肠肿瘤形成及组织炎症的影响

Effect ofω-3polyunsaturated fatty acids on intestinal tumor formation and tissue inflammation in obese mice

目的探讨ω-3多不饱和脂肪酸(PUFAs)对肥胖小鼠肠肿瘤形成及组织炎症的影响。方法采用高脂饮食构建肥胖小鼠模型,随后分为对照组(A组)、肥胖小鼠肠肿瘤模型组(B组)、二十碳五烯酸干预组(C组)和二十二碳六烯酸干预组(D组),每组6只。记录小鼠体重和肿瘤数量,HE染色观察结肠肿瘤组织病理学变化,ELISA法检测血清TNF-α、IL-6和IL-1β水平,实时荧光定量PCR检测附睾脂肪和结肠组织中TNF-α、IL-6和IL-1βmRNA表达,Western blot法检测增殖细胞核抗原(PCNA)、NF-κB、磷酸化NF-κB、精氨酸酶1(Arg-1)、F4/80、CD163和诱导型一氧化氮合酶(iNOS)蛋白表达。结果与A组相比,B组、C组和D组小鼠体重下降(P<0.05或P<0.01),C组和D组小鼠体重高于B组(P<0.05)。C组和D组结肠肿瘤数量以及PCNA、NF-κB和磷酸化NF-κB蛋白表达低于B组(P<0.05)。C组和D组血清TNF-α、IL-6和IL-1β水平低于B组(P<0.05或P<0.01)。C组和D组结肠、附睾脂肪组织中TNF-α、IL-6和IL-1βmRNA表达低于B组(P<0.05或P<0.01)。C组和D组附睾脂肪组织中Arg-1蛋白表达高于B组,而iNOS和F4/80蛋白表达低于B组(P<0.05)。C组和D组结肠组织中CD163、iNOS和F4/80蛋白表达均低于B组(P<0.05)。结论ω-3PUFAs可以抑制肥胖相关肠肿瘤的生长,改善脂肪组织和结肠炎症,影响巨噬细胞的浸润和极化。

Objective To investigate the effect ofω-3polyunsaturated fatty acids(PUFAs)on the intestinal tumor formation and tissue inflammation in obese mice model.Methods High fat dietinduced obesity model was established and then randomly and equally divided into four groups of A(controls),B(obesity-related intestinal tumor mouse model),C(eicosapentaenoic acid intervention)and D(docosahexaenoic acid intervention).The weight and tumor number of the mice were recorded.The pathological change of colon tumor tissues was observed using HE staining.Serum levels of TNF-α,IL-6and IL-1βwere measured by ELISA method.The mRNA expressions of TNF-α,IL-6and IL-1βin the epididymal fat and colon tissues were determined by real-time fluorescence quantitative PCR.The protein expressions of proliferating cell nuclear antigen(PCNA),NF-κB,phosphorylated NF-κB,arginase 1(Arg-1),F4/80,CD163and inducible nitric oxide synthase(iNOS)were detected by Western blot.Results Compared with group A,the weight of the mice was decreased in groups of B,C and D(P<0.05or P<0.01),which was higher in groups of C and D than that in group B(P<0.05).The number of colon tumor and protein expressions of PCNA,NF-κB and phosphorylated NF-κB in groups of C and D were lower than those in group B(P<0.05).Serum levels of TNF-α,IL-6and IL-1βin groups of C and D were lower than those in group B(P<0.05or P<0.01),and the mRNA expressions of TNF-α,IL-6and IL-1βin the epididymal fat and colon tissues in groups of C and D were also lower than those in group B(P<0.05or P<0.01).Compared with group B,the protein expression of Arg-1was increased,while the protein expressions of iNOS and F4/80were decreased in the epididymal fat tissues in groups of C and D(P<0.05).The protein expressions of CD163,iNOS and F4/80in the colon tissues in groups of C and D were significantly lower than those in group B(P<0.05).Conclusionω-3PUFAs can suppress the growth of obesity-related intestinal tumor,improve the adipose tissues and colon inflammation,and affect the infiltration and polarization of macrophages.