【摘要】 目的:观察七叶皂苷钠通过阻断转化生长因子-β(TGF-β)介导的信号通路对急性肺损伤大鼠肺纤维化和炎症因子的影响。方法:采用60只SPF级健康Wistar大鼠,随机分为空白组、模型组、阳性对照组、实验组(七叶皂苷钠组),每组各15只。造模成功后实验组经尾静脉注射七叶皂苷钠注射液(4 mg/kg),空白组、模型组注射生理盐水(4 mL/kg),阳性对照组按照3.6 mg/kg的剂量给予强的松,每天给药1次,连续14 d,于给药后第14天处死各组大鼠,并按设计要求留取标本。结果:模型组大鼠的肺系数、炎症程度、纤维化程度均高于其他3组(P<0.05);阳性对照组与实验组大鼠的肺系数、炎症程度、纤维化程度均高于空白组,但差异无统计学意义(P>0.05);阳性对照组与实验组大鼠的的肺系数、炎症程度、纤维化程度对比,差异均无统计学意义(P>0.05)。阳性对照组与实验组大鼠的炎症程度相较于模型组明显减轻,与空白组则无明显差异;模型组大鼠双肺丧失了绝大部分肺泡结构,其纤维化程度相较于阳性对照组和实验组大鼠明显增加(P<0.05);阳性对照组与实验组大鼠肺泡间隔的胶原沉积情况较轻,其纤维化程度与空白组相比无明显差异阳性对照组、实验组大鼠肺泡灌洗液中炎症因子TNF-α、IL-1β、IL-6、IL-10均低于模型组(P<0.05);实验组大鼠泡灌洗液中IL-6明显低于阳性对照组(P<0.05)。模型组大鼠肺组织TGF-β、Smad2、Smad3、α-sma表达均高于空白组(P<0.05),而实验组大鼠肺组织TGF-β、Smad2、Smad3、α-sma表达均低于模型组。结论:七叶皂苷钠能明显改善大鼠肺纤维化的生理指标,降低肺纤维化模型大鼠肺泡灌洗液中炎性因子水平,能明显抑制TGF-β/Smad信号通路,为临床治疗急性肺损伤提供了新的选择和研究途径。更多还原

【Abstract】 Objective: To observe the effects of Sodium Aescinate on pulmonary fibrosis and inflammatory factors in acute lung injury rats by blocking TGF-β-mediated signaling pathway. Methods: A total of 60 SPF healthy Wistar rats were randomly divided into blank group, model group, positive control group and experimental group, with 15 rats in each group. After successful modeling, the experimental group was intravenously injected with sodium aescinate injection（4 mg/kg）, and the blank group and model group were injected with normal saline（4 mL/kg）. The positive control group was given prednisone at a dose of 3.6 mg/kg, once a day for 14 days. Rats in each group were sacrificed on the 14^thday after administration, and specimens were collected according to the design requirements. Results: The lung coefficient, inflammation degree and fibrosis degree of the rats in the model group were higher than those of the other three groups（P<0.05）. The lung coefficient, inflammation degree and fibrosis degree of the rats in the positive control group and the experimental group were higher than those in the blank group, but the difference was not statistically significant（P>0.05）. There was no significant difference in lung coefficient, inflammation degree and fibrosis degree between the positive control group and the experimental group（P>0.05）. Compared with the model group, the degree of inflammation in the positive control group and the experimental group was significantly reduced, and there was no significant difference with the blank group. The bilateral lungs of the model group lost most of the alveolar structure, and the degree of fibrosis was significantly higher than that of the positive control group and the experimental group（P<0.05）. The collagen deposition in the alveolar septa of the rats in the positive control group and the experimental group was lighter, and the degree of fibrosis was not significantly different from that in the blank group. The levels of the inflammatory factors TNF-α, IL-1β, IL-6 and IL-10 in the bronchoalveolar lavage fluid of the rats in the positive control group and experimental group were lower than those in the model group（P<0.05）. The level of IL-6 in the bubble lavage fluid of rats in the experimental group was significantly lower than that in the positive control group（P<0.05）.The expressions of TGF-β, Smad2, Smad3 and α-sma in the lung tissue of the rats in the model group were higher than those in the blank group（P<0.05）, while the expressions of TGF-β, Smad2, Smad3 and α-sma in the lung tissue of the rats in the experimental group were all lower in the model group（P <0.05）. Conclusion:Sodium Aescinate can significantly improve the physiological indicators of pulmonary fibrosis in rats, reduce the level of inflammatory factors in the bronchoalveolar lavage fluid of pulmonary fibrosis model rats, and can significantly inhibit the TGF-β/Smad signaling pathway, which is provide a new option and research approach for clinical treatment of acute lung injury.更多还原