熊果酸抑制矽肺大鼠转化生长因子β1、白介素1的表达及其作用机制

Inhibitive Effect and Mechanism of Ursolic Acid on TGF-β1 and IL-1 Expression in Silicosis Rat

[目的]研究熊果酸抑制矽肺大鼠转化生长因子β1(TGF-β1)和白介素1(IL-1)的表达及其可能作用机制。[方法]80只Wistar雄性大鼠,随机分为对照组、模型组、熊果酸组、溶剂对照组,每组20只。除对照组外,其余组采用非暴露法气管内一次性注入二氧化硅(Si O2)悬液(250 mg/kg)建立动物矽肺模型。熊果酸组自注射Si O2后每天灌胃熊果酸40 mg/kg,溶剂对照组每天灌胃质量分数为0.6%的羧甲基纤维素钠溶液(10 m L/kg),对照组灌胃生理盐水(10 m L/kg),连续56 d。ELISA法检测各组大鼠血清中IL-1和TGF-β1的质量浓度(后称"含量"),免疫组织化学法和Western blot法检测肺组织磷酸化蛋白激酶B(p-AKT1)表达情况。[结果]与对照组比较,模型组和溶剂对照组大鼠IL-1和TGF-β1含量、p-AKT1表达明显增加,差异均有统计学意义(P<0.05)。与模型组和溶剂对照组比较,熊果酸组大鼠IL-1和TGF-β1含量、p-AKT1表达下降,差异有统计学意义(P<0.05)。四组间分别进行各时间点的IL-1、TGF-β1含量与p-AKT1线性回归分析,各时间点相关系数均r>0(P<0.01)。[结论]熊果酸减少TGF-β1和IL-1表达,减缓矽肺的发展进程,其作用可能与抑制p-AKT1激活有关。

[Objective] To study possible mechanism of inhibitive effect of ursolic acid on transforming growth factor beta-1（TGF-β1） and interleukin-1（IL-1） expressions in silicosis rats. [Methods] Totally 80 Wistar rats were randomly divided into control, model, ursolic acid, and solvent control groups, with 20 rats each. Except the control group, the other groups were induced by intratracheal instillation of silica（Si O2）（250 mg/kg）. Then 40 mg/kg ursolic acid, 0.6%（mass fraction） sodium carboxymethyl cellulose（10 m L/kg） solution, and normal saline（10 m L/kg） were given to ursolic acid, solvent control, and control groups respectively for 56 consecutive phosphorylated days. ELISA was used to detect serum IL-1 and TGF-β1 in rats. Immunohistochemical and Western blot assays were applied to detect phosphorated protein kinase B（p-AKT1） in lung tissues. [Results] Compared with the control group, the contents of IL-1 and TGF-β1 and the expression of p-AKT1 were significantly higher in the model group and the solvent control group（P〈0.05）. However, down-regulations were observed in the ursolic acid group compared with the model group and the solvent control group（P〈0.05）. According to the linear regression analysis, the correlation coefficients of the contents of IL-1 and TGF-β1 with p-AKT1 at four time points were greater than 0（P〈0.01）. [Conclusions] Ursolic acid could reduce the expression of IL-1 and TGF-β1 and alleviate the development of silicosis probably by inhibiting p-AKT1 activation.