十枣汤对肺纤维化大鼠肺组织层粘连蛋白和血小板衍生生长因子表达的影响

Effect of Shizao Decoction on Expression of LN and PDGF in Lung Tissues of Rats with Pulmonary Fibrosis

目的:通过检测博来霉素诱导肺纤维化大鼠肺组织层粘连蛋白(LN)和血小板衍生生长因子(PDGF)的水平,初步探讨十枣汤抗肺纤维化可能的作用机制。方法:以雄性无特定病原体(SPF)级SD大鼠为研究对象,将96只SD大鼠随机分为6组:空白组、模型组、吡啡尼酮组、十枣汤低剂量组、十枣汤中剂量组、十枣汤高剂量组,每组16只。采用气管内注入博莱霉素的方法建立肺纤维化模型。造模后第2天,空白组及模型组大鼠每日灌胃生理盐水2 mL,吡非尼酮组每日灌胃吡非尼酮溶液2 mL,十枣汤低、中、高剂量组分别灌胃低、中、高浓度的十枣汤2 mL,每周3次,其余时间每日灌胃生理盐水2 mL。于第14天各组随机处死8只大鼠(模型组、十枣汤低剂量组7只),第28天处死其余大鼠,取肺组织。HE染色观察肺组织病理学变化,ELISA法检测肺组织中LN和PDGF的浓度。结果:与空白组比较,模型组出现典型肺纤维化改变,肺组织中LN和PDGF表达水平明显升高(均P<0.01);与模型组比较,各药物观察组肺纤维化程度明显减轻,肺组织LN和PDGF的表达水平明显降低(均P<0.01);十枣汤高剂量组肺组织LN和PDGF的表达水平较其他组显著降低(均P<0.01)。吡啡尼酮组与十枣汤中剂量组大鼠肺组织LN及PDGF表达水平差异无统计学意义(均P>0.05)。结论:十枣汤能够改善博来霉素所致大鼠肺纤维化,其作用机制可能与抑制肺组织中LN和PDGF的表达有关。

Objective:To investigate the underlying mechanism of Shizao Decoction against bleomycin-induced idiopathic pulmonary fibrosis in rats based on the levels of laminin(LN)and platelet-derived growth factor(PDGF).Methods:A total of 96 SPF SD rats were randomized into the blank group,model group,pirfenidone group,and low-dose,medium-dose group,and high-dose Shizao Decoction groups,with 16 in each group.Pulmonary fibrosis was induced in rats by intratracheal injection of bleomycin.From the second day after modeling,rats in the blank group and the model group were given(i.g.)2 mL normal saline each day and those in the pirfenidone group received(i.g.)2 mL of pirfenidone solution each day.Moreover,and 2 mL of low-,medium-,and high-concentration of Shizao Decoction was given(i.g.)to the three Shizao Decoction groups,respectively,three times a week,and 2 mL of normal saline was given for the rest of the time.Eight rats(7 in model group and low-dose Shizao Decoction group)were killed in each group on the 14th day and the rest were killed on the 28th day.Lung tissues were collected and the pathological changes were observed based on hematoxylin-eosin(HE)staining.The concentration of LN and PDGF in lung tissues was detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the blank group,the model group showed typical pulmonary fibrosis and increase in the concentration of LN and PDGF in lung tissues(P<0.01).Compared with the model group,the administration groups demonstrated significant alleviation of pulmonary fibrosis and obvious reduction in the concentration of LN and PDGF in lung tissues(P<0.01).The concentration of LN and PDGF in lung tissues in high-dose Shizao Decoction group was lower than that in other groups(P<0.01).The levels of LN and PDGF in lung tissues were insignificantly different between the pirphenidone group and the medium-dose Shizao Decoction group(P>0.05).Conclusion:Shizao Decoction relieves the bleomycin-induced pulmonary fibrosis in rats by inhibiting the expression of LN and PDGF in lung tissues.