文章摘要
陈霞,米爱红,秦丽.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[J].安徽医药,2023,27(1):50-54.
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
  
DOI:10.3969/j.issn.1009-6469.2023.01.011
中文关键词: 丹参  糖尿病肾病  Notch1/RBP-Jκ/Msx2信号通路  钙磷代谢  大鼠, Sprague-Dawley
英文关键词: Salvia miltiorrhiza  Diabetic nephropathy  Notch1/recombination signal-binding protein for immunoglobulin kappa J region/Msh homeobox 2 signal pathway  Calcium and phosphorus metabolism  Rats, Sprague-Dawley
基金项目:
作者单位
陈霞 河南省直第三人民医院肾内科河南郑州 450000 
米爱红 河南省直第三人民医院肾内科河南郑州 450000 
秦丽 河南省直第三人民医院肾内科河南郑州 450000 
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中文摘要:
      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[( 126.29±13.16)mg2/dL2比( 71.06±13.48)mg2/dL2],肾脏组织中 Notch1[( 1.06±0.15)比( 0.31±0.06)]、 RBP-Jκ[( 1.15±0.03)比( 0.37±0.04)]、 Msx2[( 0.69±0.05)比( 0.23±0.04)]、 Jagged1、N1-ICD蛋白水平升高( P<0.05);与模型组相比,丹参素低剂量组 24 h尿 mALB水平,血清中钙、磷、钙×磷,肾脏组织中 Notch1,RBP-Jκ、 N1-ICD蛋白水平降低,丹参素(中、高)剂量组、糖适平组 FBG、24 h尿 mALB水平,血清中钙、磷、钙×磷,肾脏组织中 Notch1、 RBP-Jκ、Msx2、Jagged1、N1-ICD蛋白水平降低( P<0.05)。结论丹参素可通过调控 Notch1/RBP-Jκ/Msx2信号通路发挥对糖尿病肾病大鼠钙磷沉积现象的改善。
英文摘要:
      Objective 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 AnimalTechnology 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 for4 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 urinarymALB; the levels of serum calcium and phosphorus were measured by automatic biochemical analyzer; hematoxylin eosin (HE) stainingwas 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 groupwere higher (P<0.05). After administration, the rats in the model group had depressed spirit, decreased activity, slow response, weakeyes, excessive drinking and eating, increased urinary output, and easily wet bedding; there were glomerular hypertrophy, basementmembrane thickening, obvious fibrosis and inflammatory infiltration; in addition, there were a lot of black granules between the elasticfibers of the intima and the media of the renal aorta, and the calcification of the vessels was serious. With the increase of Danshensu(low, medium and high) administration, the activity of rats gradually returned to normal, and the slow reaction was decreased, however,there were still excessive drinking and eating, increased urination, and easily wet bedding; the glomerular hypertrophy, basement membrane thickening, tissue fibrosis and inflammation were relieved; the black granules between the elastic fibers of the intima and the media of the renal aorta decreased, and the calcification of the blood vessels slightly relieved. Compared with those in the control group,the levels of FBG and 24 h urinary mALB, serum calcium [(2.89±0.14) mmol/L vs. (2.24±0.09) mmol/L], phosphorus [(3.48±0.28) mmol/ L vs. (2.49±0.21) mmol/L], calcium × phosphorus [(126.29±13.16) mg2/dL2 vs. (71.06±13.48) mg2/dL2], the protein levels of Notch1 [(1.06±0.15) vs. (0.31±0.06)], RBP-Jκ [(1.15±0.03) vs. (0.37±0.04)], Msx2 [(0.69±0.05) vs. (0.23±0.04)], Jagged1, and N1-ICD in kidney tissue of the model group were higher (P < 0.05). Compared with those in the model group, the level of 24-hour urinary mALB, serum calcium, phosphorus, calcium×phosphorus, the protein levels of Notch1, RBP-Jκ, and N1-ICD in kidney tissue in the low-dose Danshensu group were lower, the levels of FBG and 24-hour urinary mALB, serum calcium, phosphorus, calcium × phosphorus, the protein levels of Notch1, RBP-Jκ, Msx2, Jagged1, and N1-ICD in kidney tissue in the Danshensu (medium and high) dose group and Tangshiping group were lower (P < 0.05).Conclusion Danshensu can inhibit the Notch1/RBP-Jκ/Msx2 signaling pathway to alleviate the calcium and phosphorus deposition in diabetic nephropathy rats.
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