摘要
目的研究益气活血解毒方抑制梗阻性肾病大鼠肺脏淋巴管生成及淋巴管内皮细胞表型转化的作用。方法选用雄性Wistar大鼠80只,随机分为假手术组(Sham)、单侧输尿管结扎组(UUO)、依普利酮治疗组(EPL)和中药治疗组(TCM),每组20只。采用结扎左侧输尿管复制梗阻性肾病大鼠模型。术后给予含药饲料(依普利酮100 mg·kg^(-1)·d^(-1)、益气活血解毒方免煎颗粒1.92 g·kg^(-1)·d^(-1))。180天后摘取大鼠肺脏。HE及天狼星红染色观察肺组织病理,Western blot、免疫组化及免疫荧光染色法检测淋巴管内皮透明质酸受体-1(LYVE-1)、血管内皮生长因子受体3(VEGFR3)、血管内皮生成因子-C(VEGF-C)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)、I型胶原蛋白(Collagen I)、白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、核因子κB(NF-κB)、血清糖皮质激素诱导蛋白激酶-1(SGK-1)以及盐皮质激素受体(MR)等指标表达情况。结果UUO大鼠肺脏呈现明显的纤维化改变,胶原沉积明显增多,伴有淋巴管增多及大量炎性细胞浸润,α-SMA、Vimentin、LYVE-1、VEGFR3、VEGF-C、IL-1β、MCP-1、TNF-α、NF-κB、p-SGK-1、MR及CollagenⅠ表达增强(P<0.05)。益气活血解毒方治疗后纤维化程度、淋巴管生成及炎症损伤等均明显减轻。结论益气活血解毒方可通过调控MR/NF-κB/VEGF-C通路,抑制肺淋巴管生成及淋巴管内皮细胞表型转化,减轻梗阻性肾病诱导的肺脏纤维化。
Objective To study the effect of Yiqi Huoxue Jiedu decoction on inhibiting pulmonary lymphangiogenesis and phenotypic transformation of lymphatic endothelial cells in rats with obstructive nephropathy.Methods Eighty male Wistar rats were selected and randomly divided into sham-operated group(Sham),unilateral ureteral ligation group(UUO),eplerenone treatment group(EPL)and traditional Chinese medicine treatment group(TCM),20 rats in each group.The rat model of obstructive nephropathy was established by ligating the left ureter.After surgery,they were given medicated feed(eplerenone 100 mg·kg^(-1)·d^(-1),Nojian Granules of Yiqi Huoxue Jiedu decoction 1.92 g·kg^(-1)·d^(-1)).Rat lungs were harvested after 180 days.HE and Sirius red staining,and the expression of lymphatic vessel endothelial hyaluronic acid receptor-1(LYVE-1),vascular endothelial growth factor receptor 3(VEGFR3),vascular endothelial growth factor-C(VEGF-C),alpha-smooth muscle actin(α-SMA),Vimentin,Collagen I,interleukin-1β(IL-1β),monocyte chemotactic protein 1(MCP-1),tumor necrosis factor-α(TNF-α),nuclear factorκB(NF-κB),serum and glucocorticoid-induced protein kinase-1(SGK-1)and mineralocorticoid receptor(MR)were detected by Western blot,immunohistochemistry and immunofluorescence staining.Results The lungs of UUO rats showed obvious fibrotic changes,with significantly increased collagen deposition,accompanied by increased lymphatic vessels and a large number of inflammatory cell infiltration.The expressions ofα-SMA,Vimentin,LYVE-1,VEGFR3,VEGF-C,IL-1β,MCP-1,TNF-α,NF-κB,p-SGK-1,MR and Collagen I were enhanced(P<0.05).The degree of fibrosis,lymphangiogenesis and inflammatory injury were significantly reduced after Yiqi Huoxue Jiedu decoction treatment.Conclusion Yiqi Huoxue Jiedu decoction can reduce pulmonary fibrosis induced by obstructive nephropathy by regulating MR/NF-κB/VEGF-C pathway,inhibiting pulmonary lymphangiogenesis and phenotypic transformation of lymphatic endothelial cells.
作者
刘子骞
杨帆
高晓萌
刘令今
陈格格
郝娟
许庆友
Liu Ziqian;Yang Fan;Gao Xiaomeng;Liu Lingjin;Chen Gege;Hao Juan;Xu Qingyou(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Institute of Integrative Medicine,Hebei University of Chinese Medicine,Shijiazhuang,050091,China;Hebei Key Laboratory of Integrative Medicine on Liver-kidney Patterns Research,Shijiazhuang 050091,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第4期1350-1357,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会面上项目(82174317):醛固酮刺激MR活化诱导UUO大鼠对侧肾脏淋巴管生成及益气解毒化瘀中药的保护作用,负责人:许庆友
河北省教育厅河北省高等学校科学技术研究项目青年基金项目(QN2020116):NLRP3炎症小体在UUO诱导肺脏损伤中的作用机制及中药保护作用,负责人:杨帆
河北中医学院优秀青年教师基础研究计划项目(YQ2020007):基于“整体观念”探讨UUO诱导巨噬细胞表型转化在肺脏损伤中的作用及中药干预,负责人:杨帆
关键词
梗阻性肾病
淋巴管生成
肺纤维化
益气活血解毒方
Obstructive nephropathy
Lymphangiogenesis
Pulmonary fibrosis
Yiqi Huoxue Jiedu decoction
