STAT6蛋白在实验性结肠炎大鼠中的表达及其对细胞因子IFN-γ和IL-4的影响

Expression of STAT6 in the intestinal mucosa of rats with TNBS induced experimental colitis and its influence on cytokines IFN-γ and IL-4

目的研究信号转导和转录激活因子6(STAT6)在实验性结肠炎大鼠中的表达及其对IFN-γ和IL-4的影响,评价益生菌对其表达的干预。方法将30只雄性SD大鼠随机分为对照组(C组)、模型组(D1组)、美沙拉嗪组(D2组)、VSL#3组(D3组)、联合治疗组(美莎拉嗪+益生菌,D4组)。应用TNBS法建立大鼠溃疡性结肠炎(ulcerative colitis,UC)模型。观察大鼠的一般情况,比较结肠组织炎症程度。HE法染色观察大鼠结肠黏膜组织形态学变化。Western免疫印迹(Western blotting)法检测大鼠结肠组织中STAT6、p STAT6、IL-4和IFN-γ蛋白水平的表达。结果 (1)STAT6和p STAT6蛋白在模型组大鼠结肠组织中表达明显增加,与对照组比较,差异有统计学意义(P<0.01)。(2)STAT6和p STAT6在VSL#3组、美莎拉嗪组、联合治疗组的表达降低;其中p STAT6表达与模型组比较,差异有统计学意义(P<0.05)。(3)STAT6和p STAT6表达量在各组中变化与促炎因子IFN-γ呈显著正相关,而与IL-4呈显著负相关。结论 STAT6参与了UC大鼠的病理生理过程;益生菌可能通过下调非磷酸化和磷酸化STAT6的表达,改变Th1/Th2的比值,进而缓解和治疗TNBS诱导的大鼠结肠炎,其作用机制可能与益生菌VSL#3通过抑制大鼠结肠组织STAT6的表达有关。

Objective To investigate the expression of STAT6 in the intestinal mucosa of rats with experimental coli- tis and its influence on cytokines IFN-γ, IL-4 and to evaluate its response to the treatment with probiotics VSL#3. Methods Thirty adult Sprague-Dawley rats were averagely randomized into five groups： control group （C group）, mod- el group （D1 group）, Mesalazine treatment group （D2 group）, probiotics VSL#3 treatment group （D3 group） and com- bined treatment group [ probiotics VSL#3 plus Mesalazine （ D4 group） ]. Experimental colitis model was established by TNBS. Except for control group, rats in the other groups were subjected to induction of colitis. The expressions of STAT6, pSTAT6, IL-4, IFN-γ in the intestinal mucosa of rats were detected by Western blotting method. Results （ 1 ） Compared with control group, the expressions of STAT6 and pSTAT6 were increased significantly in model group （P 〈 0.01 ）. （2） Compared with model group, the expressions of STAT6 and pSTAT6 in VSL#3 group, mesalazine group, and combined group were significantly lower （ P 〈 0.05 ）. （ 3 ） Positive correlation existed between STAT6 and IFN-γ in all groups （ P 〈 0.05 ） and negative correlation existed between STAT6 and IL-4 in all groups （P 〈 0.05）. Conchmion The higher expression of STAT6 may induce the Thl/Th2 imbalance, which may result in ulcerative colitis （UC）. Probiotic VSL#3 could effectively reduce TNBS-induced colitis in rats and suppress abnormal expression of STAT6, which may be one of the mechanisms for treatment of UC.