辣椒素受体表达水平上调改善糖尿病大鼠体内炎性反应及血管粥样硬化程度

    Improvement effect of TRPV1 expression levels on inflammatory reaction and vascular atherosclerosis degree in vivo in diabetic rats

    • 摘要:
      目的 分析辣椒素受体(TRPV1)表达水平对糖尿病大鼠模型体内炎症反应水平以及对血管粥样硬化的影响。
      方法 将30只糖尿病模型SD大鼠随机分成2组:辣椒素组(予以辣椒素成分饲料喂养)、模型组(予以高脂高糖饲料喂养),每组15只。另选取普通SD大鼠15只作为正常组(予以普通饲料喂养)。比较3组大鼠TNF-α、IFN-γ、IL-2、IL-6、IL-10等炎性因子浓度的差异。应用Western blot检测并比较3组外周血单核细胞的TRPV1表达水平。比较3组大鼠主动脉粥样硬化程度及斑块面积的差异。应用Pearson相关分析评估各项炎性因子水平与外周血单核细胞TRPV1表达水平的相关程度。多元Logistic回归模型分析与糖尿病大鼠血管粥样硬化发生相关的危险因素。受试者工作特征曲线(ROC)评估外周血单核细胞TRPV1表达水平预测糖尿病大鼠血管粥样硬化的价值。
      结果 与正常组相比,模型组大鼠TNF-α、IFN-γ、IL-2、IL-6水平较高,IL-10水平较低(均P<0.05);与其它两组比较,辣椒素组大鼠TNF-α、IFN-γ、IL-2、IL-6水平均最低,IL-10水平最高(P<0.05,P<0.01)。与正常组相比,辣椒素组大鼠外周血单核细胞的TRPV1表达水平较高(P<0.05),而模型组无显著差异。与正常组相比,模型组大鼠主动脉粥样斑块面积较大(P<0.05),而辣椒素组大鼠主动脉粥样斑块面积最小(P<0.05)。3组大鼠各项炎性因子TNF-α、IFN-γ、IL-2、IL-6水平与外周血单核细胞TRPV1表达水平呈负相关,IL-10与TRPV1表达水平呈正相关(均P<0.05)。多元Logistic回归模型分析显示辣椒喂养及TRPV1表达水平时糖尿病大鼠血管粥样硬化发生的保护性因素(P<0.05)。ROC曲线显示,TRPV1表达水平截断值为0.56,预测的AUC为0.872,敏感度为86.3%,特异度为80.6%。
      结论 糖尿病大鼠通过辣椒喂养上调TRPV1表达水平能有效抑制体内炎症反应水平,改善血管粥样硬化发生。

       

      Abstract:
      AIM To analyze the improvement effect of TRPV1 expression levels on inflammatory reaction and vascular atherosclerosis degree in vivo in diabetic rats.
      METHODS A total of 30 SD diabetic rats were randomLy divided into 2 groups: pepper ingredients group (feeding with pepper ingredients) and model group (feeding with high-sugar and high-fat feed), with 15 rats in each group. Fifteen normal SD rats served as normal group (feeding with regular feed). The indexes of serum TNF-α, IFN-γ, IL-2, IL-6 and IL-10 levels were compared between the 3 groups. The expression levels of TRPV1 at peripheral blood monocytes were measured by Western blot and were compared between the 3 groups. The degree of aortic atherosclerosis and plaque area were also compared between the 3 groups. The correlation between the various inflammatory factors levels and the TRPV1 expression levels in peripheral blood monocytes was assessed by Pearson correlation analysis. The risk degrees of the above indexes for the vascular atherogenesis in diabetic rats were analyzed by multivariate logistic regression analysis and the clinical values of the TRPV1 expression levels for the vascular atherosclerosis in diabetic rats were analyzed by the receiver operating characteristic (ROC) curve.
      RESULTS Compared with those in normal group, the serum levels of TNF-α, IFN-γ, IL-2, IL-6 and IL-10 in model group were higher, and IL-10 was lower (P<0.05) and the serum levels of TNF-α, IFN-γ, IL-2, IL-6 in pepper ingredients group were lowe, and IL-10 was higher (P<0.05, P<0.01). Compared with those in normal group, the TRPV1 expression levels in peripheral blood monocytes in pepper ingredients group were higher (P<0.05), but no significant difference was observed in the TRPV1 expression levels in model group. Compared with those in normal group, the aortic atherosclerotic plaque areas in model group were higher (P<0.05) and the aortic atherosclerotic plaque areas in model group were smaller (P<0.05). The levels of inflammatory factors TNF-α, IFN-γ, IL-2, IL-6 in three groups of rats were negatively correlated with the expression level of TRPV1 in peripheral blood monocytes, while IL-10 was positively correlated with the expression level of TRPV1 in peripheral blood monocytes (all P<0.05). By the multivariate Logistic regression analysis, feeding pepper ingredients and TRPV1 expression levels were the protective factors for the vascular atherogenesis in diabetic rats (P<0.05). The cut-off point of TRPV1 expression levels (0.56) was identified by the ROC curve to predict the vascular atherogenesis in diabetic rats, with the sensitivity of 86.3% and specificity of 80.6% (AUC=0.872).
      CONCLUSION The up-regulated TRPV1 expression levels of diabetic rats fed with pepper ingredients inhibit the inflammatory reaction and improve the vascular atherosclerosis.

       

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