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
The aim of this study was to determine the effect of dexamethasone（DEX） on renal ischemia/reperfusion injury（IRI）. C57BL/6 mice were randomly divided into Sham group, IRI group and DEX group. The mice in IRI and DEX groups subjected to renal ischemia for 60 min, were treated with saline or DEX（4 mg/kg, i.p.） 60 min prior to I/R. After 24 h of reperfusion, the renal function, renal pathological changes, activation of extracellular signal-regulated kinase（ERK） and glucocorticoid receptor（GR）, and the levels of iNOS and eNOS were detected. The results showed DEX significantly decreased the damage to renal function and pathological changes after renal IRI. Pre-treatment with DEX reduced ERK activation and down-regulated the level of iNOS, whereas up-regulated the level of eNOS after renal IRI. DEX could further promote the activation of GR. These findings indicated GR activation confers preconditioning-like protection against acute IRI partially by up-regulating the ratio of eNOS/iNOS.
【目的】探讨吲哚-3-原醇(indol-3-carbinol,I3C)对人低分化鼻咽癌细胞株CNE-2的作用及其机制。【方法】将对数生长期的CNE-2细胞分成空白对照组和I3C组。空白对照组细胞常规培养,I3C组细胞培养体系中加入I3C(50μmol/L)。各组细胞培养48 h后,采用四甲基偶氮唑盐(MTT)法检测细胞增殖;Annexin V-碘化丙啶/异硫氰酸荧光素(PI/FITC)检测细胞凋亡,Real-time PCR检测细胞中胞外信号调节激酶(ERK)和Bax、Bcl-2基因表达;Western blot法检测细胞中ERK、p-ERK、Bax、Bcl-2蛋白表达,Caspase3活性试剂盒检测Caspase3活性。【结果】I3C组与空白对照组比较,CNE-2细胞增殖率显著下降(P<0.05),凋亡率显著升高(P<0.05),Real-time PCR检测显示I3C组与空白对照组比较,ERK m RNA表达无显著性差异,但Bax m RNA表达水平显著增高(P<0.001),Bcl-2 m RNA表达水平显著下降(P<0.05)。Western blot法检测显示,I3C组与空白对照组比较,ERK总蛋白无明显变化(P>0.05),但p-ERK和Bcl-2蛋白表达显著减少(P<0.05),Bax蛋白表达和Caspase3活性显著增加(P<0.05)。【结论】吲哚-3-原醇能通过抑制ERK信号传导通路激活而抑制CNE-2细胞增值和促进CNE-2细胞凋亡。
