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目的:探讨低分子肝素减轻急性百草枯中毒大鼠肺纤维化的可能作用机制。方法:55只雄性SD大鼠随机分成正常对照组5只,模型组25只,低分子肝素组25只。模型组与低分子肝素组禁食1 h后经口一次性给予百草枯75 mg/kg灌胃制成百草枯大鼠肺纤维化模型;低分子肝素组造模后皮下注射低分子肝素1 000 u/d,对照组与模型组给予0.2 mL/d生理盐水皮下注射。正常对照组于第1天,模型组、低分子肝素组于造模后1,3,7,14,28 d分别取5只大鼠肺组织行病理HE染色,取血清检测转化生长因子-β1、基质金属蛋白酶-9水平。结果:模型组血清转化生长因子-β1水平第3天明显升高;基质金属蛋白酶-9水平于第7天逐渐上升,第28天明显升高,与正常对照组比较差异均有统计学意义(P<0.05或P<0.01)。低分子肝素组第3天起转化生长因子-β1、基质金属蛋白酶-9水平较模型组降低(P<0.05或P<0.01)。病理结果示低分子肝素组肺泡壁出血减轻,肺纤维化程度较模型组减少。结论:低分子肝素可能通过影响转化生长因子-β1水平,减少基质金属蛋白酶-9的合成,减轻大鼠纤维化程度。
Objective: To investigate the possible mechanism of low molecular weight heparin on pulmonary fibrosis in acute paraquat poisoning rats. Methods: Fifty-five male SD rats were randomly divided into normal control group (n = 5), model group (n = 25) and low molecular weight heparin group (n = 25). The rats in model group and low molecular weight heparin group were fasted for one hour and were given paraquat 75 mg / kg orally once a day to make paraquat-induced rat model of pulmonary fibrosis. Low molecular weight heparin group was subcutaneously injected with low molecular weight heparin 1 000 u / d, control group and model group given 0.2 mL / d normal saline subcutaneously. The normal control group on the first day, the model group, low molecular weight heparin group at 1, 3, 7, 14, 28 d after modeling, respectively, five rats lung tissue pathological HE staining, serum detection of transforming growth factor-β1 , Matrix metalloproteinase-9 levels. Results: The level of TGF-β1 in model group was significantly increased on the 3rd day. The level of MMP-9 increased gradually on the 7th day and increased significantly on the 28th day, which was significantly different from the normal control group P <0.05 or P <0.01). The level of transforming growth factor-β1 and matrix metalloproteinase-9 in low molecular weight heparin group was lower than that in model group on the third day (P <0.05 or P <0.01). Pathological results showed that the low molecular weight heparin group reduced alveolar wall hemorrhage, pulmonary fibrosis than the model group decreased. Conclusion: Low molecular weight heparin may reduce the level of TGF-β1, decrease the synthesis of matrix metalloproteinase-9 and reduce the degree of fibrosis in rats.