Background Diarrhea is a common clinical feature of ulcerative colitis resulting from unbalanced intestinal fluid and salt absorption and secretion.The Cl-/HCO3-exchanger SLC26A3 is strongly expressed in the mid-distal colon and plays an essential role in colonic Cl-absorption and HCO3-secretion.Sic26a3 expression is up-regulated by lysophosphatidic acid （LPA） in vitro.Our study was designed to investigate the effects of LPA on SLC26A3 expression and the diarrheal phenotype in a mouse colitis model.Methods Colitis was induced in C57BL/6 mice by adding 4％ of dextran sodium sulfate （DSS） to the drinking water.The mice were assigned to LPA treatment DSS group,phosphate-buffered saline （PBS） treatment DSS group,DSS only group and untreated mice with a completely randomized design.Diarrhea severity was evaluated by measuring mice weight,disease activity index （DAI）,stool water content and macroscopic evaluation of colonic damage.The effect of LPA treatment on Sic26a3 mRNA level and protein expression in the different groups of mice was investigated by quantitative PCR and Western blotting.Results All mice treated with DSS lost weight,but the onset and severity of weight loss was attenuated in the LPA treatment DSS group.The increases in stool water content and the macroscopic inflammation score in LPA treatment DSS group were significantly lower compared to DSS control group or PBS treatment DSS group （（18.89±8.67）％ vs.（28.97±6.95）％ or （29.48±6.71）％,P=0.049,P=0.041,respectively and 2.67±0.81 vs.4.5±0.83 or 4.5±0.54,P=0.020,P=0.006,respectively）,as well as the increase in DAI （P=0.004,P=0.008,respectively）.LPA enema resulted in higher Slc26a3 mRNA and protein expression levels compared to PBS-treated and untreated DSS colitis mice.Conclusion LPA increases Slc26a3 expression in the inflamed intestine and reduces diarrhea severity in DSS-induced colitis,suggesting LPA might be a therapeutic strategy in the treatment of colitis associated diarrhea.
Xu LihongXiao FangHe JiayiLan XiaoqinDing QiangLi JunhuaUrsula SeidlerZheng YongTian Dean
目的通过构建炎症和非炎症肝干细胞增殖模型,观察肝干细胞在炎症增殖环境和非炎症增殖环境中的细胞学特性差异。方法以2-乙酰氨基芴+肝大部切除术构建非炎症环境肝干细胞增殖模型,以2-乙酰氨基芴+四氯化碳构建炎症环境肝干细胞增殖模型。苏木精-伊红(HE)染色观察肝脏组织结构变化;免疫组化法观察肝干细胞EpCAM、CD133、OV6的表达,运用Image-Pro Plus 6.0软件分析平均吸光度值;透射电镜观察肝干细胞超微结构变化。结果成功建立炎症、非炎症环境肝干细胞增殖模型。HE染色:非炎症环境肝干细胞增殖模型大鼠肝脏未见炎性细胞;炎症环境肝干细胞增殖模型大鼠肝脏见大量炎性细胞。免疫组化:EpCAM、CD133、OV6表达阳性的肝干细胞均可在炎症和非炎症环境肝干细胞增殖模型中被发现,炎症环境肝干细胞增殖模型EpCAM、CD133、OV6表达量较非炎症环境肝干细胞增殖模型高(P<0.05)。透射电镜:两种肝干细胞增殖模型中均可见3型肝干细胞亚型;炎症环境增殖模型异型肝干细胞数较非炎症环境增殖模型多(P<0.05)。结论较非炎症肝干细胞增殖环境,炎症环境中EPCAM^+、CD133^+、OV6^+的肝干细胞增多,肝干细胞超微结构的异常可能在炎症早期就已出现。
