低分子肝素对大鼠百草枯中毒致肺纤维化的作用研究

Study of LMWH against paraquat poisoning-induced pulmonary fibrosis in rats

目的探讨低分子肝素对大鼠百草枯中毒致肺纤维化的作用及可能的机制。方法采用百草枯(40 mg/kg)灌胃方法建立中毒模型,将54只SD大鼠随机分为健康对照组、百草枯中毒组(中毒组)、低分子肝素治疗组(治疗组),治疗组每只大鼠于百草枯灌胃后30 min皮下注射1 000 U/kg的低分子肝素钠,分别于第7、14和28天检测血清转化生化因子β1(TGF-β1)、Ⅲ型前胶原肽(PⅢP)、羟脯氨酸(HYP),并观察各时间点肺组织病理改变。结果与对照组比较,中毒组及治疗组在第7、14和28天TGF-β1、PⅢP、HYP均明显升高(P<0.05);与中毒组比较,治疗组在第7、14、28天TGF-β1、PⅢP、HYP水平较中毒组明显下降(P<0.05)。肺组织病理学发现,给予百草枯染毒后,大鼠肺纤维化程度随时间的延长逐渐加重,间质中成纤维细胞逐渐增多,胶原沉积逐渐增加,肺泡结构破坏逐渐加重;给予低分子肝素治疗后,大鼠肺泡结构破坏减少,间质中成纤维细胞及胶原沉积减少。结论低分子肝素可以通过减少TGF-β1、PⅢP、HYP的生成,减轻百草枯致肺纤维化的程度。

Objective To investigate the effects and the mechanisum of the low molecular weight heparin on pulmonary fibrosis in rats induced by paraquat poisoned. Methods Established the model of garaged paraquat （40 mg/kg）, the 54 SD rats were randomly divided into normal control group ,paraquat poisoning group （poisoning group） and low molecular weight heparin group （treatment group）, the treatment group were treated subcutaneously 1000U/kg of low molecular weight heparin 30 minutes after gavaged, the levels of TGF-β1 ,P βP,HYP were measured at 7 d,14 d,28 d and observed the pathological changes in the lung tissue. Results Compared with control group, the levels of TGF-~ 1 ,P III P, HYP obviously increased in poisoning group and treatment group at 7 d, 14 d,28 d （P 〈 0. 05 ）, compared with treatment group, the levels of TGF-β1 ,PⅢP,HYP obviously decreased in treatment group at 7 d,14 d,28 d （P 〈0. 05 ）. Pulmonary fibrosis after gavaged paraquat interstitial fibroblasts,collagen deposition and alveolar structural damage were gradually increased, alveolar structural damage,interstitial fibroblasts and collagen deposition reduced after administration of low molecular weight heparin. Conclusion Low molecular weight heparin can reduce TGF-131, pIllp, HYP generation, and the degree of paraquat-induced pulmonary fibrosis.