人参皂苷Rg3通过RhoA/ROCK/NLRP3通路改善糖尿病肾病小鼠肾小球内皮损伤机制的实验研究  

Experimental Study on the Mechanism of Ginsenoside Rg3 Improving Glomerular Endothelial Injury in Diabetic Nephropathy Mice Through RhoA/ROCK/NLRP3 Pathway

作　　者：刘美燕 李娜 赵淑洁 郑倩倩 霍云涛 LIU Meiyan;LI Na;ZHAO Shujie;ZHENG Qianqian;HUO Yuntao(Department of Nephrology,Xianxian Hospital of Traditional Chinese Medicine Hospital,Hebei Cangzhou 062250,China;Department of Nephrology,Dingzhou People’s Hospital,Hebei Dingzhou 073000,China;Department of Traditional Chinese Medicine,Hebei Handan City Cixian People’s Hospital,Hebei Handan 056500,China)

机构地区：[1]献县中医医院肾病科,河北沧州062250 [2]定州市人民医院肾内科,河北定州073000 [3]邯郸市磁县人民医院中药科,河北邯郸056500

出　　处：《现代检验医学杂志》2025年第2期123-128,共6页Journal of Modern Laboratory Medicine

基　　金：河北省中医药类科学研究课题计划项目(2024200)。

摘　　要：目的探究人参皂苷Rg3是否可通过Ras同源基因家族成员A(RhoA)/RHO关联卷曲螺旋蛋白激酶(ROCK)/含NLR家族Pyrin域蛋白3(NLRP3)通路改善糖尿病肾病(DN)小鼠肾小球内皮损伤。方法将40只小鼠随机分为4组:对照组、DN组、人参皂苷(人参皂苷Rg3)组及RhoA/ROCK通路抑制(FD)组,每组10只。血糖仪检测小鼠空腹血糖(FPG);ELISA检测尿蛋白、尿素氮(BUN)和血肌酐(SCr)水平;PAS染色检测肾小球形态结构并评估肾小球损伤指数(GDI);免疫荧光染色检测肾小球血小板-内皮细胞黏附分子(PECAM-1或CD31)、血管性血友病因子(vWF)、RhoA,ROCK及细胞焦亡相关蛋白NLRP3蛋白表达;Western blotting检测肾小球中细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)与细胞焦亡相关的炎性因子白细胞介素-1β(IL-1β)及IL-18蛋白表达。结果与对照组相比,DN组小鼠FPG,尿蛋白、SCr及BUN水平增加,差异具有统计学意义(t=17.59~43.81,均P<0.05);肾小球结构明显损伤且GDI增加(t=20.73,P<0.05),肾小球中CD31,RhoA,ROCK,NLRP3表达增加,vWF表达减少;肾组织中ICAM-1,VCAM-1,IL-1β及IL-18表达增加,差异具有统计学意义(t=27.95~40.10,均P<0.05)。与DN组相比,人参皂苷组小鼠FPG,尿蛋白、BUN及SCr水平减少,差异具有统计学意义(t=14.87~20.33,均P<0.05);肾小球结构损伤改善且GDI减少(t=19.80,P<0.05);肾小球CD31,RhoA,ROCK及NLRP3表达减少,vWF表达增加,FD组小鼠肾组织ICAM-1,VCAM-1,IL-1β及IL-18表达减少,差异具有统计学意义(t=12.62~39.68,均P<0.05)。结论人参皂苷Rg3可通过下调RhoA/ROCK/NLRP3通路,改善DN小鼠肾小球内皮损伤及细胞焦亡水平。Objective To investigate whether ginsenoside Rg3 can ameliorate glomerular endothelial injury in diabetic nephropathy(DN)mice through Ras homologous gene family member A(Rho A)/Rho-associated coiled-coil forming protein kinase,(ROCK1)/NLR family pyrin domain protein 3(NLRP3)pathway.Methods Forty mice were randomly divided into 4 groups:control group,DN group,ginsenoside(ginsenoside Rg3)group and RhoA/ROCK pathway inhibition(FD)group,with 10 mice in each group.Fasting blood glucose(FBG)was measured by glucose meter.The levels of urinary protein,urea nitrogen(BUN)and serum creatinine(SCr)were detected by ELISA.PAS staining was used to detect glomerular morphology and structure and to evaluate glomerular injury index(GDI).The expression of platelet-endothelial cell adhesion molecule(PECAM-1 or CD31),von Willefibrilia factor(vWF),RhoA,ROCK and NLRP3 protein related to pyrodeath were detected by immunofluorescence staining.Western blotting detected the expression of intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),the inflammatory factor interleukin-1β(IL-1β)and IL-18 protein in the glomerulus.Results Compared with the control group,the levels of FPG,urinary protein,BUN and SCr in DN group were increased,and the differences were statistically significant(t=17.59~43.81,all P<0.05).The glomerular structure was significantly damaged and GDI was increased(t=20.73,P<0.05).The expressions of CD31,RhoA,ROCK and NLRP3 in glomeruli were increased,while the expression of vWF was decreased.The expressions of ICAM-1,VCAM-1,IL-1βand IL-18 in renal tissues were increased,and the differences were statistically significant(t=27.95~40.10,all P<0.05).Compared with the DN group,the levels of FPG,urinary protein,BUN and SCr in ginsenoside group were decreased,and the differences were statistically significant(t=14.87~20.33,all P<0.05).The damage of glomerular structure was improved and GDI was decreased(t=19.80,P<0.05),the expression of CD31,RhoA,ROCK and NLRP3 in glomerular was decreased,and the exp

关 键 词：糖尿病肾病 肾小球 内皮损伤 人参皂苷RG3 Ras同源基因家族成员A/RHO关联卷曲螺旋蛋白激酶/含NLR家族Pyrin域蛋白3 细胞焦亡 

分 类 号：R-332[医药卫生]