不同比例ω-3/ω-6多不饱和脂肪酸对DSS诱导大鼠急性结肠炎的影响

Effects of different ratios of ω-3/ω-6 polyunsaturated fatty acids on experimental acute colitis in rats

目的:探讨不同比例ω-3/ω-6多不饱和脂肪酸对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导大鼠急性结肠炎影响及其可能的作用机制.方法:32只1月龄♂SD大鼠随机分为4组,每组8只,A:普通饲料对照组,B:ω-3/ω-6PUFA 1∶1组、C:ω-3/ω-6 PUFA 1∶3组,D:ω-3/ω-6 PUFA 1∶30组.4组大鼠不同饲料喂养6 wk;随后B、C、D组大鼠自由饮用3%DSS溶液7 d,诱发急性结肠炎模型;A组大鼠自由引用普通水7 d.比较各组大鼠结肠炎症状评分、病理炎症评分和结肠组织前列腺素E2(prostaglandin E2,PGE2)、核因子-kB(nuclear factor-kB,NF-kB)、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、血清白介素-6(interleukin-6,IL-6)的含量.结果:B组大鼠结肠炎症程度积分显著低于C、D组,分别为2.8±1.2、4.3±1.1、5.6±1.3(P<0.05,P<0.01).B组大鼠结肠炎病理学评分显著低于C、D组,分别为3.2±2.0、35.0±28.8、27.0±25.8(P<0.01,P<0.01).B、C组大鼠结肠组织中PGE2含量低于D组,分别为443.4ng/100g组织±67.3 ng/100g组织、419.5ng/100g组织±52.6 ng/100 g组织、541.2±68.5(ng/100 g组织)(P<0.05,P<0.01).B、C组大鼠结肠组织中TNF-α含量低于D组,分别为189.2 ng/100g组织±27.0 ng/100 g组织、173.2 n g/100g组织±50.2 n g/100 g组织、270.3 ng/100g组织±49.1 ng/100 g组织(P<0.01,P<0.01).B组大鼠血清中IL-6含量低于C、D组,分别为97.1 ng/L±8.2 ng/L、129.1 ng/L±5.5 ng/L、125.4 ng/L±19.6 ng/L(P<0.01,P<0.05).B、C、D大鼠结肠组织中NF-kB含量分别为497.9 ng/100g组织±50.7 ng/100 g组织、569.1 ng/100g组织±121.2 ng/100 g组织、582.5 ng/100g组织±123.1 ng/100 g组织,无统计学差异.结论:提高以ω-3/ω-6 PUFA的比例对于DSS诱导的大鼠急性结肠炎症具有保护作用,尤其是当ω-3/ω-6 PUFA比例提高到1∶1保护作用最明显.随着ω-3 PUFA的比例升高,ω-3/ω-6PUFA1∶1组较ω-3/ω-6 PUFA1:30组大鼠的炎症评分、病理评分以及相关的炎症因子如PGE2、TNF-α、IL-6都有所下降.向饮食中添加适量ω-6 PUFA或可成为治疗炎症性肠病新方向.

AIM： To investigate the effect of different ratios of ω-3/ω-6 of polyunsaturated fatty acids （PUFAs） on acute colitis induced with dextran sulfate sodium （DSS） in rats and explore the pos- sible mechanisms. METHODS： Thirty-two male SD rats were randomly divided into four groups （n = 8 for each）： A （control）, B （ω-3/ω-6, 1：1）, C （ω-3/ω-6, 1：3） and D （ω-3/ω-6, 1：30）. After six weeks of feed- ing with different diets, acute colitis in rats in groups B, C and D were induced by giving 3% DSS in drinking water for seven days. Then all the rats were sacrificed. Overall inflammatoryseverity score and histological damage score were calculated. The levels of prostaglandin E2 （PGE2）, tumor necrosis factor-α （TNF-α, nuclear transcription factor kappa B （NF-κB） in the colon, and the level of interleukin-6 （IL-6） in serum were measured by ELISA. RESULTS： The overall inflammatory severity score in group B was significantly lower than those in groups C and D （2.8± 1.2 vs 4.3 ± 1.1, 5.6 ± 1.3, P 〈 0.05, P 〈 0.01）. The histological damage score in group B was also significantly lower than those in groups C and D （3.2 ± 2.0 vs 35.0 ± 28.8, 27.0 ± 25.8, P 〈 0.01 for both）. The levels of PGE2 and TNF-α in the colon were significantly lower in groups B and C than in group D [443.4± 67.3 （ng/100 g tissue）, 419.5± 52.6 （ng/100 g tissue） vs 541.2 ±68.5 （ng/100 g tissue）, P 〈 0.05, P 〈 0.01; 189.2 ± 27.0 （ng/100 g tissue）, 173.2 ＋ 50.2 （ng/100 g tissue） vs 270.3 ± 49.1 （ng/100 g tissue）, P 〈 0.01 for both）. The level of IL-6 in serum was significantly lower in group B than in groups C and D （97.1 ng/L± 8.2 ng/L vs 129.1 ng/L± 5.5 ng/L, 125.4 ng/L± 19.6 ng/L, P 〈 0.01, P 〈 0.05）. There were no statistical differences in the level of nuclear NF-κB between groups B, C and D [497.9± 50.7 （ng/100 g tissue）, 569.1 ± 121.2 （ng/100 g tissue）, 582.5 ± 123.1 （ng/100 g tissue）]. CONCLUSION： Higher ratios of ω-3/ω-6 PUFAs have a more significant protective effect against acute colitis, especially when the ratio is 1：1. The overall inflammatory severity score, histological damage score, the levels of PGE2 and TNF-α in colon and the level of IL-6 in serum are significantly lower in the 1：1 （ ω-3/ω-6） group than in the 1：30 group. Adding moderate amount of ω-3 PUFA may be a new way to treat IBD.