异甘草酸镁对博来霉素诱导肺纤维化大鼠治疗作用及其机制  

Therapeutic Effect and Mechanism of Magnesium Isoglycyrrhizinate in Treatment of Bleomycin-induced Pulmonary Fibrosis in Rats

作　　者：高瑕 代文静[1] 曾军[1] 冯同 李万成[1] GAO Xia;DAI Weng-jing;ZENG Jun;FENG Tong;LI Wan-cheng(Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Chengdu Medical College,Chengdu 610000,China)

机构地区：[1]成都医学院第一附属医院呼吸与危重医学科,成都610000

出　　处：《临床误诊误治》2021年第7期101-107,共7页Clinical Misdiagnosis & Mistherapy

基　　金：国家临床重点专科建设培育科室专项科研项目(CYFY2018GLPHX01)。

摘　　要：目的探讨异甘草酸镁(MgIG)对博来霉素(BLM)诱导肺纤维化大鼠治疗作用及其机制。方法选择24只成年雄性SD大鼠,随机将其分为Control组、BLM组、BLM+MgIG组和BLM+甲泼尼龙琥珀酸钠(MTH)组4组各6只大鼠。BLM组、BLM+MgIG组和BLM+MTH组予BLM构建肺纤维化大鼠模型,Control组予0.9%氯化钠注射液。造模成功24 h后,Control组和BLM组予0.9%氯化钠注射液,BLM+MgIG组予MgIG注射液,BLM+MTH组予注射用MTH。连续给药28 d后处死大鼠,测定血清超氧化物歧化酶(SOD)和丙二醛(MDA)含量;肺组织切片病理检查,采用Masson染色及肺纤维化程度评分评价大鼠肺组织纤维化程度,免疫组织化学检查肺组织转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)表达水平,蛋白质印迹法检测肺组织TGF-β1、TNF-α及IFN-γ蛋白水平。结果肺纤维化程度评分Control组低于其他3组,BLM组高于BLM+MgIG组和BLM+MTH组,BLM+MgIG组低于BLM+MTH组,差异有统计学意义(P<0.05)。Control组血清SOD高于其他3组,血清MDA低于其他3组,肺组织TGF-β1和TNF-α表达低于其他3组,肺组织IFN-γ表达高于其他3组;BLM组血清SOD低于BLM+MgIG组和BLM+MTH组,血清MDA高于BLM+MgIG组和BLM+MTH组,肺组织TGF-β1和TNF-α表达高于BLM+MgIG组和BLM+MTH组,肺组织IFN-γ表达低于BLM+MgIG组和BLM+MTH组;BLM+MgIG组血清SOD高于BLM+MTH组,血清MDA低于BLM+MTH组,肺组织TGF-β1和TNF-α表达低于BLM+MTH组,肺组织IFN-γ表达高于BLM+MTH组,差异有统计学意义(P<0.05)。大鼠肺组织TGF-β1和TNF-α蛋白Control组表达量较低,BLM组表达量升高,BLM+MgIG组和BLM+MTH组表达量低于BLM组;大鼠肺组织IFN-γ蛋白Control组表达量较高,BLM组表达量降低,BLM+MgIG组表达量较BLM组明显增加。结论MgIG能改善BLM诱导肺纤维化大鼠肺纤维化,机制可能与减轻氧化应激,抑制炎性因子表达,促进抗纤维化因子分泌有关。Objective To discuss the therapeutic effect and mechanism of Magnesium Isoglycyrrhizinate(MgIG)in treatment of Bleomycin(BLM)-induced pulmonary fibrosis in rats.Methods Twenty-four adult male SD rats were randomly divided into control group,BLM group,BLM+MgIG group and BLM+Methylprednisolone Sodium Succinate(MTH)group(n=6 in each group).BLM,BLM+MgIG and BLM+MTH groups were injected with BLM to establish rat models of pulmonary fibrosis,while control group was injected with 0.9%Sodium Chloride Injection.After successful modeling for 24 h,control and BLM groups were injected with 0.9%Sodium Chloride Injection,and BLM+MgIG group was injected with MgIG Injection,while BLM+MTH group was injected with MTH.All rats were sacrificed after continuous infusion for 28 d.Contents of serum superoxide dismutase(SOD)and malondialdehyde(MDA)were determined.Pathological examination for lung tissue sections was performed.The degree of lung tissue fibrosis in rats was evaluated by Masson staining and pulmonary fibrosis score.Expression levels of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)in lung tissues were determined by immunohistochemistry.Levels of TGF-β1,TNF-αand IFN-γin lung tissues were detected by Western blotting.Results Pulmonary fibrosis score in control group was the lowest,followed by BLM+MgIG group,BLM+MTH group and BLM group,and the differences were statistically significant(P<0.05).In control group,serum SOD content was significantly higher,while serum MDA content was lower than those in other three groups;expressions of TGF-β1 and TNF-αin lung tissues were significantly lower than those in other three groups,while IFN-γexpression in lung tissues was significantly higher than that in other three groups.in BLM group,serum SOD content was significantly lower than those in BLM+MgIG and BLM+MTH groups,while serum MDA content was significantly higher than those in BLM+MgIG and BLM+MTH groups;expressions of TGF-β1 and TNF-αin lung tissues were significantly high

关 键 词：肺纤维化 大鼠 博来霉素 异甘草酸镁 超氧化物歧化酶 丙二醛 转化生长因子-Β1 Γ-干扰素 

分 类 号：R563[医药卫生—呼吸系统] R-33[医药卫生—内科学]