肺复康合剂对大鼠肺纤维化的抑制作用及相关机制

The inhibition role and related mechanism of Feifukang mistura on rat pulmonic fibrosis

目的探讨肺复康合剂对大鼠肺纤维化的抑制作用及相关机制。方法 40只SD雄性大鼠随机分为对照组、模型组、造模+肺复康组、单纯肺复康组。模型组、造模+肺复康组气管灌注博莱霉素(5 mg/kg),而对照组和单纯肺复康组气管灌注同等剂量无菌生理盐水,随后对照组和模型组生理盐水灌胃28 d,造模+肺复康组、单纯肺复康组肺复康合剂灌胃(12 ml/kg)28 d。给药28 d后麻醉处死,计算各组肺系数、肺干重/体重变化,检测肺组织羟脯氨酸(HYP)、一氧化氮(NO)、肺动脉血浆NO2-/NO3-含量、丙二醛(MDA)水平,以及Western印迹法检测诱导型NO合酶(i NOS)、结缔组织生长因子(CTGF)、磷酸化细胞外信号调节激酶(ERK)表达水平。结果与对照组相比,模型组肺系数、肺干重/体重、HYP、NO、NO2-/NO3-、MDA、i NOS、CTGF、p-ERK表达均明显增高(P<0.05);与模型组相比,造模+肺复康组肺系数、肺干重/体重、HYP、NO、NO2-/NO3-、MDA、i NOS、CTGF、p-ERK表达水平均明显降低,肺纤维化指标均明显改善;单纯肺复康组与对照组相比,上述指标没有明显变化(P>0.05)。结论肺复康合剂通过抑制促纤维化因子i NOS、CTGF表达及ERK信号通路,减少博莱霉素所致的应激损伤、病理变化、胶原合成,发挥抑制肺纤维化的药理作用。

Objective To study the inhibition role and related mechanism of Feifukang mistura on rat pulmonic fibrosis. Methods40 male SD rats were randomized into control,model,model+ Feifukang,Single Feifukang groups. The rats in model and model+Feifukang groups were given intratracheal injection of bleomycin( 1 mg / kg),and the rats in control and single Feifukang groups were given intratracheal injection of normal saline alone as the equivalent dose. The rats were treated Feifukang mistura( 12 ml / kg intragastrically) for 28 d in model+ Feifukang and single Feifukang groups. The lung coefficient,lung dry weight / body weight,hydroxyproline( HYP),nitric oxide( NO) of lung tissues,and NO2-/ NO3-,malondialdehyde( MDA) of pulmonary artery plasma in all groups were measured. The expressions of nitric oxide synthase( i NOS),connective tissue growth factor( CTGF) and phosphorylation extracellular regulated protein kinase( pERK) were detected by Western blot in all groups. Results Compared with that of control group,the lung coefficient,lung dry weight /body weight,the levels of HYP,NO,NO2-/ NO3-,MDA were obviously increased,and the expression levels of i NOS,CTGF and p-ERK were significantly increased in model group( P < 0. 05); Compared with those of model group,the lung coefficient,lung dry weight / body weight,the levels of HYP,NO,NO2-/ NO3-,MDA were obviously decreased,and the expression levels of i NOS,CTGF and p-ERK were significantly decreased in model+Feifukang group,the indexes of pulmonary fibrosis were significantly improved( P<0. 05). The above parameters between the single Feifukang and the control groups were obviously changed( P > 0. 05). Conclusions Feifukang mistura inhibits the bleomycin-induced oxidative stress,histological alterations and collagen depositions and plays the pharmacological effects of anti-pulmonary fibrosis via the inhibition of the pro-fibrotic cytokine i NOS,CTGF expressions and the ERK pathway.