异甘草酸镁对大鼠百草枯中毒肺纤维化治疗作用的研究

目的 探讨异甘草酸镁(MgIG)对大鼠百草枯(paraquat,PQ)中毒所致肺纤维化的防治作用及可能的机制.方法 健康的SD雄性大鼠30只,随机分成5组:正常对照组、染毒对照组、MgIG低剂量(15 mg/kg)组、MgIG中剂量(30 mg/kg)组和MgIG高剂量(45 mg/kg)组;用20% PQ溶液按15 mg/kg行腹腔注射制作大鼠PQ中毒肺损伤模型,各治疗组于染毒后24 h按相应剂量MgIG行腹腔注射,正常对照组及染毒对照组注射生理盐水(按MgIG中剂量组的相应容量计算),直至死亡或被处死.于染毒后第14天全部处死,取肺组织行HE染色及Masson染色行病理学观察,并测定肺组织内羟脯氨酸(HYP)含量,同时取血清测定细胞间黏附因子-1(ICAM-1)及基质金属蛋白酶-9(MMP-9)含量.结果 所有大鼠均无自然死亡;光镜观察到染毒对照组静脉瘀血、淋巴增生、纤维母细胞增多,肺泡上皮增生明显,间质增厚.与染毒对照组相比,MgIG中剂量组的肺组织瘀血、水肿明显减轻,肺纤维化病理表现明显较轻,且肺内HYP明显下降(P均<0.01);血清中ICAM-1及MMP-9含量也明显降低(P<0.05或P<0.01).结论 MgIG中剂量对百草枯中毒大鼠肺组织纤维化损伤有一定的防治作用.

Therapeutic effects of magnesium isoglycyrrhizinate on pulmonary fibrosis induced by paraquat in rats

Objective To explore the therapeutic effect and the possible mechanism of Magnesium Isoglycyrrhizinate (MgIG) on pulmonary fibrosis induced by paraquat in rats. Methods Thirty healthy male SD rats were randomly divided into five groups: normal control group, toxicosis control group, MgIG low-dose group (15 mg/kg), MgIG medium-dose group(30 mg/kg) and MgIG high-dose group(45 mg/kg). 20% paraquat was injected peritoneally at the dose of 15 mg/kg to induce pulmonary injury in rats. MgIG was injected peritoneally in every therapeutic groups after 24 hours of intoxication,and the normal control group received saline until death or being sacrificed. Rats were sacrificed after 14 days of intoxication. HE stain and Masson stain were performed and hydroxyproline(HYP) were measured for lung specimens, and serum levels of intercellular adhesion molecule-1(ICAM-1) and matrix metalloproteinase-9(MMP-9) were measured. Results No animal died during the experiment. Venous congestion or hemorrhage,lymph hyperplasia, fibroblast hyperplasia, alveolar epithelium hyperplasia and stroma thickening in part of the lung were observed in toxicosis control group under light microscope. Compared with toxicosis control group, lung congestion and edema of MgIG medium-dose group were obviously alleviated in all therapeutcal groups. The level of HYP in lung tissues decreased significantly (P<0.01), and the levels of ICAM-1 and MMP-9 in plasma decreased as well (P<0.05 and P<0.01). Conclusion Pulmonary fibrosis induced by paraquat in rats could be alleviated by administration of medium-dose MgIG .