运动对氟中毒小鼠空肠形态结构和TLR2/NF-κB信号通路的影响

Effects of exercise on morphology and TLR2/NF-κB signal pathway in jejunum of fluorosis mice

目的探讨运动对氟中毒小鼠空肠TLR2/NF-κB信号通路的影响。方法36只3周龄ICR雄性小鼠随机分为4组:对照组、氟组、运动组和运动加氟组,对照组和运动组小鼠饮用蒸馏水,氟组和运动加氟组小鼠饮用含100 mg/L NaF(氟化钠)的蒸馏水;此外,运动组和运动加氟组的小鼠根据炮台锻炼方案进行跑台运动。6个月后对小鼠空肠的组织形态学、肠道发育指数、TLR2、NF-κB p65及炎性因子的mRNA相对表达量和蛋白水平的变化进行检测。结果与对照组相比,氟组小鼠的空肠隐窝排列稀疏,肠绒毛断裂,绒毛高度(VH)和绒腺比(VH/CD)均明显下降;TLR2、NF-κB p65、IL-1β和TNF-α的mRNA相对表达量明显增加,差异有统计学意义(P<0.05或P<0.01);同时TLR2和NF-κB p65的蛋白水平也明显升高(P<0.05),ELISA检测小鼠空肠炎性因子IL-1β,TNF-α和IL-6含量均明显上升,差异有统计学意义(P<0.01或P<0.001)。与氟组相比,运动加氟组VH和VH/CD均明显增加(P<0.01),TLR2和NF-κB p65的基因和蛋白水平均有下降趋势,但差异不具有统计学意义(P>0.05),空肠组织内IL-1β和TNF-α含量明显减少,差异有统计学意义(P<0.05或P<0.01)。结论适度运动可以改善氟诱导的肠道组织形态损伤,并且通过TLR2/NF-κB信号通路调节炎性因子的释放缓解氟中毒引起的肠道促炎反应。

Objective To investigate effects of exercise on TLR2/NF-κB and related genes in jejunum of fluorosis mice.Methods Thirty-six three-weeκ-old male ICR mice were randomly divided into four groups:control group,fluoride group,exercise group and exercise plus fluoride group.Sodium fluoride(NaF,100 mg/L)was administered to mice in the fluoride and exercise plus fluoride groups,and control and exercise mice received distilled water.In addition,the mice in the exercise group and exercise plus fluoride group had treadmill exercise according to the treadmill exercise protocol.After six months,the morphology and TLR2/NF-κB and related gene expression of jejunum in mice were detected.Results Compared with the control group,the jejunal crypt was sparse,intestinal villi were broκen,and the villi height and villi height/crypt depth(VH/CD)were significantly decreased in the fluoride group.And the relative mRNA and protein expression levels of TLR2,NF-κB p65 were significantly increased(P<0.05 or P<0.01),moreover,the contents of IL-1β,TNF-αand IL-6 in jejunum were significantly increased by ELISA(P<0.01 or P<0.001).Compared with the fluoride group,the VH and VH/CD were significantly increased in the exercise plus fluoride group(P<0.01),and gene and protein levels of TLR2 and NF-κB p65 tented to decrease,but there was no statistical significance(P>0.05).The contents of IL-1βand TNF-αin jejunum were significantly decreased(P<0.05 or P<0.01).Conclusion Moderate exercise can ameliorate the intestinal tissue morphological damage induced by fluoride,and alleviate the jejunum pro-inflammatory reaction by the TLR2/NF-κB signaling pathway to regulate the release of inflammatory factors.