灯盏花乙素调节RhoA/ROCK信号通路对糖尿病肾病大鼠肾组织损伤的影响  

Influence of Scutellarin on Renal Tissue Damage in Rats with Diabetic Nephropathy by Regulating RhoA/ROCK Signaling Pathway

作　　者：王静[1] 李敏[1] 何立明[1] 高瑞超[1] 檀增桓[1] WANG Jing;LI Min;HE Liming(Handan Central Hospital,Hebei Handan 056001,China)

机构地区：[1]河北省邯郸市中心医院,河北邯郸056001

出　　处：《河北医学》2023年第5期721-726,共6页Hebei Medicine

基　　金：河北省邯郸市科学技术研究与发展计划项目,(编号:19422083009-30)。

摘　　要：目的:探讨灯盏花乙素(Scu)调节RhoA/ROCK信号通路对糖尿病肾病(DN)大鼠肾组织损伤的影响。方法:将SD大鼠随机选择10只作为对照组(Con),其余60大鼠构建DN模型,造模成功的大鼠按随机数字表法分为5组:DN组、Scu低剂量组(Scu-L组,25mg/kg)、Scu中剂量组(Scu-M组,50mg/kg)、Scu高剂量组(Scu-H组,100mg/kg)、Scu-H+LPA组(100mg/kg Scu+50μmoL/L的RhoA/ROCK信号通路激活剂LPA)。ELISA试剂盒法检测24h尿微量白蛋白(MAU)及血清生化指标;HE染色、Masson染色观察肾组织损伤情况;RT-qPCR及Western blot检测TGF-β1、VEGF、PTEN水平;Western blot检测RhoA/ROCK通路蛋白水平。结果:Con组大鼠肾小球形态结构正常;DN组肾小球形态结构异常,肾小管出现水肿以及坏死现象,鲍曼囊出现粘连现象且出现大面积的蓝染胶原纤维沉积;Scu处理后,肾小管水肿以及坏死现象减少,肾小球形态结构变得较为规则,鲍曼囊腔缩小,且蓝染胶原纤维沉积减小。与Con组相比,DN组FBG、BUN、Scr、MAU、IL-6、TNF-α、TGF-β1、VEGF mRNA及蛋白水平、RhoA、p-ROCK/ROCK蛋白水平均显著升高(P<0.05),PTEN mRNA及蛋白水平显著下降(P<0.05);Scu处理后,FBG、BUN、Scr、MAU、IL-6、TNF-α、TGF-β1、VEGF mRNA及蛋白水平、RhoA、p-ROCK/ROCK蛋白水平均显著下降(P<0.05),PTEN mRNA及蛋白水平显著升高(P<0.05),且Scu添加剂量越高,作用效果越明显;LPA消除了Scu-H组对DN大鼠的改善作用。结论:Scu可能通过下调RhoA/ROCK信号通路减轻DN大鼠肾组织损伤。Objective:To investigate the influence of scutellarin(Scu)on renal tissue damage in diabetic nephropathy(DN)rats by regulating RhoA/ROCK signaling pathway.Methods:Ten SD rats were randomly selected as the control group,and the rest of the 60 rats were constructed as DN models,the rats with successful modeling were grouped into 5 subgroups according to random number table method:DN group,Scu-L group(25mg/kg,8 weeks),Scu-M group(50mg/kg,8 weeks),Scu-H group(100mg/kg,8 weeks),Scu-H+LPA group(100mg/kg Scu,8 weeks+50μmol/L RhoA/ROCK signaling pathway activator LPA,2 weeks).ELISA kit was used to detect 24h urine microalbumin(MAU)and serum biochemical indexes;HE staining and Masson staining were applied to observe kidney tissue damage;RT-qPCR and Western blot were applied to detect TGF-β1,VEGF,PTEN levels;Western blot was applied to detect RhoA/ROCK pathway protein levels.Results:The morphology and structure of the glomeruli in the Control group were normal;in the DN group,the glomerular morphology and structure were abnormal,the renal tubules appeared edema and necrosis,and the Bowman's capsule showed adhesion and large blue-stained collagen fiber deposits;after Scu treatment,renal tubular edema and necrosis were reduced,the morphology and structure of glomeruli became more regular,Bowman's cysts were reduced,and the deposition of blue-stained collagen fibers was decreased.Compared with the Con group,FBG,BUN,Scr,MAU,IL-6,TNF-α,TGF-β1,VEGF mRNA and protein levels,RhoA,p-ROCK/ROCK protein levels in the DN group were obviously increased(P<0.05),PTEN mRNA and protein levels were obviously decreased(P<0.05);after Scu treatment,FBG,BUN,Scr,MAU,IL-6,TNF-α,TGF-β1,VEGF mRNA and protein levels,RhoA,p-ROCK/ROCK protein levels were obviously decreased(P<0.05),PTEN mRNA and protein levels were obviously increased(P<0.05),and the higher the Scu additive dose,the more obvious the effect;LPA abolished the ameliorating effect of Scu-H group on DN rats.Conclusion:Scu may alleviate renal tissue damage in DN rats by down-regulating

关 键 词：灯盏花乙素 RhoA/ROCK信号通路 糖尿病肾病 

分 类 号：R285.5[医药卫生—中药学]