脂氧素 A4的抗结肠纤维化作用及其机制

目的：观察脂氧素A4（LX A4）的抗结肠纤维化作用，并探讨其机制。方法将32只BALB／C雄性小鼠随机分为4组，每组8只。对照组不造模，仅给予生理盐水灌肠；模型组、CS组、CS／LX A4组建立结肠炎结肠纤维化模型后，分别给予生理盐水、壳聚糖纳米粒、壳聚糖／LX A4纳米粒灌肠。10 d后取结肠组织检测疾病活动指数（DAI），HE染色法光镜下观察结肠组织组织学损伤指数（HI），免疫组化法检测结肠组织转化生长因子－β1（ TGF－β1）和Smad3蛋白表达量。结果实验第10天，与对照组比较，其余3组大鼠DAI显著升高（ P＜0．01）；CS／LX A4组大鼠DAI低于模型组，但差异无统计学意义（ P＞0．05）。无论是结肠炎症程度、病变深度，还是隐窝破坏，其余3组结肠组织HI均显著高于对照组（P＜0．05，P＜0．01），CS／LX A4组均显著低于模型组和CS组（P＜0．05，P＜0．01）。模型组结肠组织TGF－β1、Smad3表达量均较对照组显著升高（P＜0．01）；与模型组比较， CS／LX A4组和CS组结肠组织TGF－β1、Smad3表达量均明显降低（ P＜0．05），但均显著高于对照组（ P＜0．05）。结论 LX A4可以通过下调TGF－β1和Smad3的表达，减轻炎症反应，进而遏制结肠纤维化的进展。

Anti-fibrosis effect of lipoxin A4 in colon and its mechanism

Objective To observe the anti-fibrosis effect of lipoxin A4 (LX A4) in colon, and to investigate its mechanism.Methods 32 BALB/C male mice were randomly divided into 4 groups with 8 in each group.Mice in the control group were treated with saline perfusion only .Mice in the model group, CS group, CS/LX A4 group were perfused with saline, chitosan nanoparticle, chitosan/LX A4 nanoparticle, respectively, after establishing the colon fibrosis mod-els.Ten days later, all mice were sacrificed and the colon tissues of each group were collected to assess the disease activi -ty index ( DAI) and histological damage index ( HI) was evaluated by HE staining .The expressions of transforming growth factor-β1(TGF-β1) and Smad3 protein were assessed by immunohistochemical staining .Results On Day 10, DAI of the other 3 groups were significantly higher than that of the control group ( P<0.01 ) .DAI of the CS/LX A4 group was lower than that of the model group while no statistical difference was observed (P>0.05).Degree of colon inflammation, depth of lesions and crypt destruction in the other 3 groups were all significantly higher than those in the control group ( P<0.05, P<0.01), and these indices in the CS/LX A4 group were all lower than those in the model and CS group (P<0.05, P<0.01).Furthermore, the levels of TGF -β1 and Smad3 in the model group were significantly elevated com-pared with the control group (P<0.01), while those in the CS/LX A4 and CS group were decreased notably compared with the model group (P<0.05), but were notably higher compared with the control group (P<0.05).Conclusion LX A4 can suppress colon fibrosis progression by alleviating the inflammatory response through the downregulation of TGF -β1 and Smad3 expression.