苗药地锦草对肝纤维化模型大鼠的改善作用及机制研究  

Ameliorative effects and mechanisms of Miao medicine Euphorbia humifusa on hepatic fibrosis model rats

作　　者：文维农 安祯祥 何远利 吴闵 何松 WEN Weinong;AN Zhenxiang;HE Yuanli;WU Min;HE Song(The First Clinical Medical College,Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China;Dept.of Gastroenterology,the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China;Dept.of Geriatrics,the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China)

机构地区：[1]贵州中医药大学第一临床医学院,贵阳550001 [2]贵州中医药大学第一附属医院消化内科,贵阳550001 [3]贵州中医药大学第一附属医院老年病科,贵阳550001

出　　处：《中国药房》2025年第4期407-413,共7页China Pharmacy

基　　金：国家自然科学基金项目(No.82160893,No.81760865);国家中医药管理局第五批全国中医临床优秀人才研修项目(No.国中医药人教函[2022]1号);贵州省卫生健康委科学技术基金项目(No.gzwkj2024-120);贵州省中医药管理局中医药、民族医药科学技术研究项目(No.QZYY-2024-014);贵州中医药大学中医脾胃病科技创新人才团队建设项目(No.贵中医TD合字[2022]005号)。

摘　　要：目的探讨苗药地锦草对肝纤维化(HF)模型大鼠的改善作用及机制。方法将38只大鼠按随机数字表法分为对照组(生理盐水,n=7),模型组(生理盐水,n=7),地锦草低、中、高剂量组(0.675、1.35、2.70 g/kg,n=6)和水飞蓟宾组(阳性对照,18.9 mg/kg,n=6)。除对照组外,其余各组大鼠均腹腔注射四氯化碳构建HF模型。造模成功后,各组大鼠灌胃相应药物/生理盐水,每天1次,连续30 d。末次给药后,计算大鼠肝指数,观察其血清中肿瘤坏死因子α(TNF-α)、白细胞介素17(IL-17)、IL-1β、IL-6、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、羟脯氨酸(HYP)水平,观察其肝组织形态与HF变化,检测其肝组织中转化生长因子β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)水平,检测肝组织中α-SMA及TNF-α/NF-κB信号通路相关蛋白以及TNF-α、NF-κB p65 mRNA表达。结果与模型组比较,各给药组大鼠肝指数,血清中TNF-α、IL-17、IL-1β、IL-6、ALT、AST、HYP水平,肝组织中NF-κB p65 mRNA相对表达量,肝组织中TNF-α、α-SMA蛋白表达水平及NF-κB p65蛋白磷酸化水平,以及地锦草中、高剂量组大鼠的肝组织中α-SMA、TGF-β1表达水平和地锦草高剂量组大鼠肝组织中阳性染色百分比、TNF-αmRNA相对表达量均显著降低(P<0.05或P<0.01);各给药组大鼠肝组织中IκBα蛋白表达水平均显著升高(P<0.05或P<0.01);各给药组大鼠肝组织病理变化及HF程度均有不同程度改善。结论地锦草可能通过抑制TNF-α/NF-κB信号通路激活来缓解大鼠HF。OBJECTIVE To investigate the ameliorative effects and mechanisms of Miao medicine Euphorbia humifusa on hepatic fibrosis(HF)model rats.METHODS Thirty-eight rats were randomly assigned according to a random number table into control group(normal saline,n=7),model group(normal saline,n=7),E.humifusa low-,medium-and high-dose groups(0.675,1.35,2.70 g/kg,n=6),and silybin group(positive control,18.9 mg/kg,n=6).All groups except the control group were subjected to HF induction via intraperitoneal injection of carbon tetrachloride.After modeling,rats were administered their respective drugs/normal saline by gavage,once a day,for 30 days.At the last medication,the liver index was calculated,and serum levels of tumor necrosis factor-α(TNF-α),interleukin-17(IL-17),IL-1β,IL-6,alanine transaminase(ALT),aspartate transaminase(AST),and hydroxyproline(HYP)were measured.Liver morphology and HF changes were observed.Levels of transforming growth factor-β1(TGF-β1)andα-smooth muscle actin(α-SMA),as well as the expressions ofα-SMA,proteins related to TNF-α/NF-κB signaling pathway,mRNA expressions of TNF-αand NF-κB p65 in liver tissue were determined.RESULTS Compared with model group,liver index,serum levels of TNF-α,IL-17,IL-1β,IL-6,ALT,AST and HYP,relative expression of NF-κB p65 mRNA,and the levels of TNF-αandα-SMA proteins and phosphorylated NF-κB p65 in liver tissues of rats from administration groups,the expressions ofα-SMA and TGF-β1 in liver tissue of rats from E.humifusa medium-dose and high-dose groups,as well as positive staining percentage and mRNA expression of TNF-αin liver tissue of rats from E.humifusa high-dose group were all decreased significantly(P<0.05 or P<0.01);IκBαprotein expression from administration groups was significantly increased(P<0.05 or P<0.01).Pathological changes and the degree of HF in the liver tissues of rats from administration groups were ameliorated to various extents.CONCLUSIONS E.humifusa may alleviate HF in rats by inhibiting the activation of the TNF-α/NF-κB signa

关 键 词：地锦草 肝纤维化 TNF-α/NF-κB信号通路 苗药 

分 类 号：R965[医药卫生—药理学]