肾浊方通过抑制肾小球内皮细胞异常血管新生治疗早期糖尿病肾脏疾病的作用机制研究  

Study on the mechanism of Shenzhuo Formula in treating early diabetes nephropathy by inhibiting the abnormal angiogenesis of glomerular endothelial cells

作　　者：张家义 陈雅欣 张玉凤 王希[2] 李伟[3] 刘雪梅[3] 万倩慧 孙振华 王文波[3] 李玉杰 ZHANG Jiayi;CHEN Yaxin;ZHANG Yufeng;WANG Xi;LI Wei;LIU Xuemei;WAN Qianhui;SUN Zhenhua;WANG Wenbo;LI Yujie(The First Clinical Medical College,Shandong University of Chinese Medicine,Jinan 250014,China;Shandong Yellow River Hospital,Jinan 250014,China;The Second Affiliated Hospital of Shandong University of Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学第一临床医学院,济南250014 [2]山东黄河医院,济南250014 [3]山东中医药大学第二附属医院,济南250014

出　　处：《长春中医药大学学报》2025年第3期272-277,共6页Journal of Changchun University of Chinese Medicine

基　　金：山东省自然科学基金(ZR2023MH300);中国博士后科学基金(2021M692750);泰山学者项目(tsqn202211356)。

摘　　要：目的 探讨肾浊方对肾小球内皮细胞迁移和血管生成的影响,以及其在治疗早期糖尿病肾脏疾病(DKD)中的潜在作用机制。方法 研究采用自发性2型糖尿病db/db小鼠(在8周龄时出现肾损伤)来研究肾浊方对DKD的影响。采用小鼠肾小球内皮细胞(MGECs)建立体外高糖模型来研究肾浊方对MGECs迁移和血管生成能力的影响。结果 肾浊方可以改善db/db小鼠的肾损伤。Western blot和免疫组织化学显示,db/db小鼠中血管内皮生长因子(VEGFA)、血管内皮生长因子受体-2(VEGFR2)、水通道蛋白-1(AQP1)和血小板-内皮细胞黏附分子(CD31)的蛋白表达水平升高,而肾浊方处理则降低了这些蛋白的表达。在MGECs高糖模型中,肾浊方可能通过改变VEGFA、VEGFR2、AQP1和CD31的表达来逆转高糖环境中MGECs的迁移能力和血管生成能力的增强。此外,药物效果随着肾浊方浓度的增加而逐渐增强。结论 肾浊方可通过抑制肾小球内皮细胞的迁移和血管生成来改善DKD早期的肾损伤,从而进一步明确了肾浊方的作用机制。此外,本研究发现DKD中AQP1的表达增加,为进一步研究DKD的潜在发病机制提供了新的视角。Objective To investigate the effect of Shenzhuo Formula on glomerular endothelial cell migration and angiogenesis,and its potential mechanisms in the treatment of early diabetic kidney disease(DKD).Methods The effect of Shenzhuo Formula on DKD was studied in spontaneous type 2 diabetes db/db mice(with kidney injury at the age of 8 weeks).The study used mouse glomerular endothelial cells(MGECs)to establish an in vitro high glucose model to investigate the effect of Shenzhuo Formula on the migration and angiogenesis ability of MGECs.Results Shenzhuo Formula ameliorated kidney damage in db/db mice.Western blot and immunohistochemistry results showed that the expression levels of vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor receptor-2(VEGFR2),aquaporin-1(AQP1),and platelet endothelial cell adhesion molecule(CD31)proteins were incresed in db/db mice,while treatment with Shenzhuo Formula reduced the expression of these proteins.In the high glucose model of MGECs,Shenzhuo Formula reversed the enhanced migration and angiogenesis ability of MGECs in a high glucose environment by altering the expression of VEGFA,VEGFR2,AQP1,and CD31.In addition,the therapeutic effect of Shenzhuo Formula was enhanced with the increase of concentrations of Shenzhuo formula.Conclusion The study indicates that Shenzhuo Formula can improve early renal injury in DKD by inhibiting glomerular endothelial cell migration and angiogenesis,thus further clarifying the mechanisms of action of Shenzhuo formula.Additionally,this study finds increased expression of AQP1 in DKD,providing new perspective for further investigating the potential pathogenesis of DKD.

关 键 词：肾浊方 糖尿病肾脏疾病 异常血管新生 血管内皮生长因子A 水通道蛋白1 

分 类 号：R259[医药卫生—中西医结合] R277.5[医药卫生—中医内科学]