甘草酸二铵对博莱霉素致肺纤维化大鼠血清iNOS及NO水平的影响及其抗肺纤维化的作用机制

Effects of diammonium glycyrrhizinate on serum iNOS and NO levels in rats with BLM-induced pulmonary fibrosis and its action mechanism of anti-pulmonary fibrosis

目的:探讨甘草酸二铵对博莱霉素(BLM)致肺纤维化的作用,阐明其抗肺纤维化的作用机制。方法:36只Wistar大鼠随机分为正常对照组、博莱霉素所致大鼠肺纤维化组(模型组)及甘草酸二铵组,每组12只。气管内一次性注入博来霉素5mg.kg-1复制肺纤维化模型。实验第2天开始,甘草酸二铵组大鼠给以甘草酸二铵75mg.kg-1.d-1干预,采用腹腔给药,对照组及模型组分别给予生理盐水(10mL.kg-1),连续给药27d。实验第28天处死所有大鼠,腹主动脉取血,测定血清中诱导型一氧化氮合酶(iNOS)及一氧化氮(NO)的水平。同时取大鼠左肺下叶,行HE染色和Masson三联染色观察肺组织病理学变化。结果:光镜下正常对照组大鼠肺组织大致正常,甘草酸二铵组大鼠肺纤维化轻微,而模型组大鼠肺纤维化改变明显。与正常对照组比较,模型组大鼠血清iNOS、NO水平明显增高(P<0.01),而甘草酸二铵组无明显变化(P>0.05);甘草酸二铵组大鼠血清iNOS、NO均低于模型组(P<0.05或P<0.01)。结论:甘草酸二铵可以下调大鼠血清中iNOS及NO的表达,从而减轻肺纤维化。

Objective To explore the effects of diammonium glycyrrhizinate on bleomycin （BLM）-induced pulmonary fibrosis （PF） and to further clarify the underlying fibrotic mechanisms. Methods 36 Wistar rats were randomly divided into normal control group, BLM-induced pulmonary fibrosis group （model group） and glycyrrhizinate group. The pulmonary fibrosis models of rats were established by injecting BLM via trachea （5 mg kg-1 once）. From the 2nd day after injection, the rats in glycyrrhizinate group were intraperitoneally injected with glycyrrhizinate （75 mg kg-1 d-1 ）, while the rats in other two groups with normal saline injection instead. On the 28th day, all rats were sacrificed, the blood samples were obstained to measure inducible nitric oxide synthase （iNOS） and nitric oxide （NO） levels. Their left lung lobe tissues were removed and used for pathological section examination. Results The pulmonary tissue of the rats in normal control group was normal, and the pulmonary fibrosis of the rats in glycyrrhizinate group was significantly lighter, and the pulmonary fibrosis of the rats in model group was severe. Compared with normal control group, the serum iNOS and NO levels of rats in model group were significantly increased （P 〈 0.01）, but the serum iNOS and NO levels of rats in glycyrrhizinate group had no changes （P〉 0.05）; the serum iNOS and NO levels of the rats in glycyrrhizinate group were lower than those in model group （P〈0. 05 or P〈0. 01）. Conclusion Diammonium glycyrrhizinate can significantly reduce the serum levels of iNOS and NO in BLM-induced pulmonary fibrosis rats and alleviate pulmonary fibrosis.