松弛素对脂多糖所致大鼠急性肺损伤肺纤维化的作用

Effect of relaxin on lipopolysaccharide-induced acute lung injury and pulmonary fibrosis in rats

目的观察松弛素对脂多糖所致大鼠肺损伤肺纤维化影响,探讨其可能的作用机制。方法 50只大鼠随机分为盐水对照组(NS组,n=10)、模型组(LPS组,n=10)、松弛素低剂量组(RLX-L组,n=10)、松弛素中剂量组(RLX-M组,n=10)、松弛素高剂量组(RLX-H组,n=10)。采用腹腔注射脂多糖法(5 mg/kg)复制急性肺损伤肺纤维化模型。造模后1 h松弛素各干预组分别开始皮下注射重组人松弛素-2 1、2、4μg/(kg·d)。14 d后测定大鼠的肺指数、羟脯胺酸含量,HE染色、masson染色观察肺纤维化程度,免疫组化法测定肺组织转化生长因子-β1(transforming growth factor beta1,TGF-β1)、Samd2蛋白的表达。结果与NS组相比,LPS组及各松弛素干预组肺指数、羟脯胺酸含量升高(P<0.05),肺纤维化评分升高,TGF-β1、Samd2表达上调(P<0.05);与LPS组对比,松弛素各干预组均能改善上述各指标(P<0.05)。结论松弛素可缓解脂多糖所致大鼠急性肺损伤肺纤维化,其机制可能是通过调节TGF-β1、Samd2的表达实现的。

Objective To observe the effects of relaxin on acute lung injury and pulmonary fibrosis induced by lipopolysaccharide in rats,and to investigate the possible mechanism.Methods Fifty rats were randomly divided into five groups,control group,LPS model group and relaxin-treatment groups(high,medium and low doses of relaxin).Acute lung injury and pulmonary fibrosis models were produced by intraperitoneal injection of Lipopolysaccharide(5 mg/kg).After one hour,the rats in relaxin-treatment groups were respectively given with 1μg/(kg·d),2μg/(kg·d)and 4μg/(kg·d)of recombinant human relaxin-2 by subcutaneous injection.After 14 days,the lung index was examined;the hydroxyproline content was measured;the degree of pulmonary fibrosis was observed after HE and Masson staining;and the expression of TGF-β1 and Samd2 were determined by immuno-histochemistry.Results Compared with the control group,the lung index and the hydroxyproline content in LPS model group and relaxin-treatment groups were significantly elevated(P<0.05),pulmonary fibrosis score was significantly increased and the expression of TGF-β1 and Samd2 were significantly upregulated(P<0.05).Compared with LPS model group,all the above indicators were significantly improved in relaxin-treatment groups(P<0.05).Conclusion Relaxin can alleviate Lipopolysaccharide-induced acute lung injury and pulmonary fibrosis in rats,and its mechanism may be achieved by regulating the expression of TGF-β1 and Samd2.