丹参素对糖尿病肾病大鼠Notch1/免疫球蛋白κJ区重组信号结合蛋白/Msh同源异型基因2信号通路及钙磷代谢的影响  

Effects of Danshensu on Notch1/recombination signal binding protein for immunoglobulin kappa J region(RBP-Jκ)/Msh homeobox 2(Msx2)signaling pathway and calcium and phosphorus metabolism in diabetic nephropathy rats

作　　者：陈霞 米爱红 秦丽 CHEN Xia;MI Aihong;QIN Li(Nephrology Department,Henan Provincial Third People's Hospital,Zhengzhou,Henan 450000,China)

机构地区：[1]河南省直第三人民医院肾内科,河南郑州450000

出　　处：《安徽医药》2023年第1期50-54,I0005,共6页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探讨丹参素通过调控Notch1/免疫球蛋白κJ区重组信号结合蛋白(RBP-Jκ)/Msh同源异型基因2(Msx2)信号通路对糖尿病肾病大鼠钙磷代谢的影响。方法2019年10月至2020年4月,北京维通利华实验动物科技有限公司购入SD大鼠,采用高糖高脂饲养4周、腹腔注射链脲佐菌素(STZ,40 mg/kg)建立糖尿病肾病大鼠模型。建模后按随机数字表法分为模型组、丹参素(低、中、高)剂量组(2.5 mL·kg^(-1)·d^(-1)、5.0 mL·kg^(-1)·d^(-1)、10.0 mL·kg^(-1)·d^(-1))、糖适平组(阳性对照,9.45 mL·kg^(-1)·d^(-1)),每组10只;对照组10只大鼠基础饲料饲养。给予相应的药物连续灌胃4周,1次/天。实验结束,观察大鼠一般情况;血糖仪检测空腹血糖(FBG)水平;24 h尿微量白蛋白(24 h尿mALB)试剂盒检测24 h尿mALB水平;全自动生化分析仪检测血清中钙、磷水平;苏木精-伊红(HE)染色检测大鼠肾脏组织形态;Von Kossa染色检测大鼠肾主动脉钙盐沉积情况;蛋白免疫印迹检测大鼠肾脏组织中Notch1、RBP-Jκ、Msx2、Jagged1、Notch1基因的胞内域(N1-ICD)蛋白水平。结果给药前,与对照组相比,造模组大鼠的FBG、24 h尿mALB水平升高(P<0.05)。给药后,模型组大鼠精神萎靡、活动减少,反应迟钝、眼神无力,多饮多食、排尿量增加、垫料易潮湿;出现肾小球肥大、基膜增厚现象,组织纤维化、炎症浸润明显;肾主动脉血管内膜、中膜弹性纤维间出现大量黑色颗粒,血管钙化严重。丹参素(低、中、高)给药组随着剂量的增加,大鼠活动逐渐恢复正常,反应迟钝减少,但仍有多饮多食、排尿量增加、垫料易潮湿现象;肾小球肥大、基膜增厚缓解,组织纤维化消失、炎症缓解;肾主动脉血管内膜、中膜弹性纤维间黑色颗粒减少,血管钙化稍缓解。与对照组相比,模型组FBG、24 h尿mALB水平,血清中钙[(2.89±0.14)mmol/L比(2.24±0.09)mmol/L]、磷[(3.48±0.28)mmol/L比(2.49±0.21)mmol/L]、钙×磷[(12Objective To investigate the effects of Danshensu on calcium and phosphorus metabolism by regulating the signal pathway of Notch1/recombination signal-binding protein for immunoglobulin kappa J region(RBP-Jκ)/Msh homeobox 2(Msx2)in diabetic nephropathy rats.Methods From October 2019 to April 2020,SD rats were purchased from Beijing Weitong Lihua Laboratory Animal Technology Co.,Ltd.The diabetic nephropathy rat model was established by feeding them with high glucose and fat for 4 weeks and injecting streptozotocin(STZ,40 mg/kg)intraperitoneally.After modeling,the rats were randomly assigned into model group,Danshensu(low,medium,and high)dose groups(2.5 mL·kg^(-1)·d^(-1),5.0 mL·kg^(-1)·d^(-1),10.0 mL·kg^(-1)·d^(-1)),and glycolipin group(positive control,9.45 mL·kg^(-1)·d^(-1)),with 10 rats in each group.In the control group,10 rats were fed basal diet.Corresponding drugs were given by gavage for 4 weeks,once a day.At the end of the experiment,the general situation of the rats was observed,and the fasting blood glucose(FBG)level was detected by the blood glucose meter;24 h urinary microalbumin(24 h urinary mALB)kit was used to detect 24 h urinary mALB;the levels of serum calcium and phosphorus were measured by automatic biochemical analyzer;hematoxylin eosin(HE)staining was used to detect the renal morphology;Von Kossa staining was used to detect calcium deposition in renal aorta of rats;and the protein levels of Notch1,RBP-Jκ,Msx2,Jagged1 and Notch1 intracellular domain in the kidney of rats were detected by Western blot.Re⁃sults Before administration,compared with those in the control group,the levels of FBG and 24 h urinary mALB in the model group were higher(P<0.05).After administration,the rats in the model group had depressed spirit,decreased activity,slow response,weak eyes,excessive drinking and eating,increased urinary output,and easily wet bedding;there were glomerular hypertrophy,basement membrane thickening,obvious fibrosis and inflammatory infiltration;in addition,there were a lot of black g

关 键 词：丹参 糖尿病肾病 Notch1/RBP-Jκ/Msx2信号通路 钙磷代谢 大鼠 Sprague-Dawley 

分 类 号：R285.5[医药卫生—中药学]