枸杞多糖对博来霉素致肺纤维化小鼠的干预作用及其机制

Inhibitory effect of lycium barbarum polysaccharide on bleomycin-induced pulmonary fibrosis in mice and its mechanisms

目的肺纤维化(pulmonary fibrosis,PF)是一组由多种病因引起的肺间质性病变,其发病机制尚未完全阐明。文中探讨枸杞多糖(LBP)对博来霉素致肺纤维化小鼠的干预作用及机制。方法将C57/BL6小鼠随机数字表法分为假手术组,模型组,地塞米松组,LBP高、中、低剂量组。假手术组用等渗盐水,其余各组用5 mg/kg博莱霉素注入小鼠气管,制作肺纤维化模型。2 d后开始给药,地塞米松组、LBP高剂量组、LBP中剂量组和LBP低剂量组分别给予地塞米松5 mg/kg、LBP 0.8g/kg、LBP 0.4 g/kg、LBP 0.2 g/kg,假手术组和模型组给予等容积等渗盐水,1次/d,连续4周。观察各组肺组织病理学变化,计算肺系数,检测肺组织羟脯氨酸(hydroxyproline,HYP)含量,RT-PCR检测肺组织纤维化相关基因COL1A1和α-SMA的表达。结果给药4周后,LBP高、中、低剂量组小鼠体重较模型组增加明显(P<0.01)。高、中剂量组肺系数[(0.847%±0.220%)、(0.859%±0.180%)]较模型组(0.887%±0.130%)明显降低(P<0.05)。高剂量组肺泡炎等级评分(3.09±0.22)较模型组(3.40±0.23)降低(P<0.05),PF等级评分(3.07±0.31)较模型组(3.57±0.27)降低(P<0.01)。高剂量组肺组织HYP含量[(0.786±0.070)μg/mg湿重]较模型组[(0.831±0.050)μg/mg湿重]明显降低(P<0.05)。与模型组比较,地塞米松组、LBP中剂量组、LBP高剂量组COL1A1表达减少(P<0.05);与模型组比较,地塞米松组、LBP中剂量组、LBP高剂量组α-SMA表达减少(P<0.05)。结论 LBP可能通过抑制COL1A1和α-SMA等基因的表达,降低肺组织HYP的含量来抑制小鼠PF的发展。

Objective Pulmonary fibrosis （PF） is a group of pulmonary interstitial pathological changes caused by various factors, and its pathogenesis is not yet fully elucidated. This article discussed the effect of lycium barbarum polysaccharide （LBP） on ble- omycin-induced PF in mice and its action mechanisms. Methods The C57/BL6 mice were randomly divided into 6 groups ： sham-operation, PF model, dexamethasone （DM）, high-dose LBP, medium- dose LBP, and low-dose LBP. The mice in the sham-operation group were injected into the trachea with isotonic saline and those in the other groups with 5 bleomycin at mg/kg for establishing the PF model. Two days after modeling, the mice in the DM and high-, medium-,and low-dose LBP groups were treated with DM at 5 mg/kg and LBP at 0.8, 0.4, and 0.2 g/kg, while those in the sham-operation and PF model groups with the same volume of isotonic saline, respectively, qd, for 4 consecutive weeks. Then, the pathological changes of the lung tissue were observed and the hydroxyproline （HYP） content in the lung tissue was detected for all the animals. RT-PCR was used to determine the relative expressions of the PF-related COL1 A1 and α-SMA genes. Results Compared with the PF models, the the high-, medium-, and low-dose LBP groups showed significant increased body weight after 4 weeks of medication （ [ 14.29 ± 0.38 ] vs [ 16.12 ± 0.37 ], [ 15.58 ± 0.25 ] and [ 15.07 ± 0.21 ] g, P 〈 0.01 ）, the high- and medium-dose groups exhibited remarkably decreased lung indexes （ [0. 887 ±0.13] vs [0. 847 ±0.22] and [0. 859 ±0. 181%, P 〈0.05）, and the high-dose group presented markedly reduced alveolitis score （ 3.40 ± 0.23 vs 3.09 ± 0.22, P 〈 0.05 ）, PF score （ 3.57 ± 0.27 vs 3.07± 0.31, P 〈 0.01 ） and HYP content （ [ 0.831 ± 0.05 ] vs [ 0.786 ± 0.07 ] μg/mg wet weight, P 〈 0.05 ）. In comparison with the model group, the DM, high-dose LBP and medium-dose LBP groups showed significantly decreased gene expressions of COL1A1 （ 1.53 ±0.13vs 1.26±0.10and0.98±0.17, P〈0.05） and α-SMA （5.67 ±0.47 vs4.19±0.28 and 2.29±0.31, P〈0.05）. Conclusion LBP can suppress the progression of bleomycin-induced pulmonary fibrosis by inhibiting the gene expressions of COL1A1 and α-SMA and decreasing the HYP content in the lung tissue.