紫丹酸B对糖尿病肾病模型小鼠糖代谢和肾功能的改善作用及机制

刘五梅; 刘永飞; 彭林; 张海红; 郭琦丽; 卢晶

doi:10.6039/j.issn.1001-0408.2023.23.07

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紫丹酸B对糖尿病肾病模型小鼠糖代谢和肾功能的改善作用及机制

药学研究 | 更新时间：2023-12-08

- 紫丹酸B对糖尿病肾病模型小鼠糖代谢和肾功能的改善作用及机制
- Effect and mechanism of tournefolic acid B on the improvement of glucose metabolism and renal function in diabetes nephropathy model mice
- 中国药房 2023年34卷第23期页码：2855-2860
- 作者机构：
  
  1.南昌医学院药学院，南昌　330052
  2.江西卫生职业学院药学系，南昌　330052
- 作者简介：
  
  讲师，硕士。研究方向：药理学。E-mail：2300616634 @qq.com
- 基金信息：
  
  江西省教育厅科学技术研究项目(GJJ2208214)
- DOI：10.6039/j.issn.1001-0408.2023.23.07
  中图分类号： R965
- 纸质出版日期：2023-12-15，
  
  收稿日期：2023-06-06，
  
  修回日期：2023-10-20，
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刘五梅,刘永飞,彭林等.紫丹酸B对糖尿病肾病模型小鼠糖代谢和肾功能的改善作用及机制 ^Δ[J].中国药房,2023,34(23):2855-2860.

LIU Wumei,LIU Yongfei,PENG Lin,et al.Effect and mechanism of tournefolic acid B on the improvement of glucose metabolism and renal function in diabetes nephropathy model mice[J].ZHONGGUO YAOFANG,2023,34(23):2855-2860.
刘五梅,刘永飞,彭林等.紫丹酸B对糖尿病肾病模型小鼠糖代谢和肾功能的改善作用及机制 ^Δ[J].中国药房,2023,34(23):2855-2860. DOI： 10.6039/j.issn.1001-0408.2023.23.07.

LIU Wumei,LIU Yongfei,PENG Lin,et al.Effect and mechanism of tournefolic acid B on the improvement of glucose metabolism and renal function in diabetes nephropathy model mice[J].ZHONGGUO YAOFANG,2023,34(23):2855-2860. DOI： 10.6039/j.issn.1001-0408.2023.23.07.

摘要

目的

研究紫丹酸B（TAB）对糖尿病肾病模型小鼠糖代谢和肾功能的改善作用及机制。

方法

采用高脂饮食联合链脲佐菌素建立糖尿病肾病模型小鼠，然后随机分为模型组、阳性对照组（维生素E，20 mg/kg）和TAB低、中、高剂量组（1、2、4 mg/kg），每组12只；另设给予普通饮食的正常对照组。各组小鼠灌胃相应药物或生理盐水，每天1次，连续4周。采用葡萄糖耐量实验、胰岛素耐量实验以及空腹血糖和血清胰岛素含量评估小鼠糖代谢功能；检测小鼠肾脏系数和肾功能相关生化指标[血清中尿酸、血尿素氮、肌酐水平和尿微量白蛋白与肌酐比值]；检测小鼠肾组织中氧化应激相关生化指标[超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）、8-羟基脱氧鸟苷（8-OHdG）]

的含量；观察小鼠肾组织的病理形态；检测小鼠肾组织中细胞外基质（ECM）沉积相关因子[转化生长因子β

（TGF-β

）、纤维连接蛋白（Fn）、Ⅳ型胶原蛋白（Col Ⅳ）]及蛋白激酶B（Akt）/核因子E

相关因子2（Nrf2）/血红素加氧酶1（HO-1）信号通路相关蛋白的表达水平。

结果

与正常对照组比较，模型组小鼠空腹血糖、葡萄糖耐量曲线下面积（AUC）、胰岛素耐量AUC、血清胰岛素含量，血清中尿酸、尿素氮、肌酐水平和尿微量白蛋白与肌酐比值，肾组织中MDA、8-OHdG含量和TGF-β

、Fn、Col Ⅳ蛋白表达水平均显著升高（

＜0.05）；肾组织中SOD、GSH-Px含量以及p-Akt、Nrf2、HO-1蛋白表达水平均显著降低（

＜0.05）；基底膜增厚、系膜基质堆积、肾小球硬化、肾小管间质纤维化明显。与模型组比较，TAB各剂量组小鼠上述指标水平均显著逆转（

＜0.05），病理改变减轻，且呈剂量依赖性。

结论

TAB可改善糖尿病肾病模型小鼠糖代谢和肾功能，减轻肾小管间质纤维化；其作用机制可能与激活Akt/Nrf2/HO-1信号通路，抑制ECM沉积，拮抗高糖诱导的氧化应激有关。

Abstract

OBJECTIVE

To explore the role and underlying mechanism of tournefolic acid B （TAB） on the improvement of glucose metabolism and renal function in diabetic nephropathy （DN） model mice.

METHODS

DN model mice were established by high-fat diet combined with streptozotocin， and then randomly divided into model group， positive control group （vitamin E， 20 mg/kg）， TAB low-dose， medium-dose and high-dose groups （1， 2， 4 mg/kg）， with 12 mice in each group； normal control group was given regular diet. Each group was given relevant medicine or normal saline intragastrically， once a day， for 4 consecutive weeks. The glucose metabolic function was estimated by fasting blood glucose， glucose tolerance test， insulin tolerance test and serum insulin concentration. The renal coefficients and biochemical indicators related to renal function [serum uric acid， blood urea nitrogen， creatinine levels， and ratio of urine microalbumin to creatinine] were detected in mice； the contents of biochemical indicators related to oxidative stress [superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， 8-hydroxydeoxyguanosine （8-OHdG）]

were determined in renal tissue of mice； the pathological morphology of renal tissue was observed； the expressions of extracellular matrix （ECM） deposition related factors [transforming growth factor β

（TGF- β

）， fibronectin （Fn）， type Ⅳ collagen （Col Ⅳ）] and protein kinase B （Akt）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway related proteins were determined in renal tissue of mice.

RESULTS

Compared with normal control group， fasting blood glucose， area under glucose tolerance curve， area under insulin tolerance curve， serum insulin content， the levels of uric acid， urea nitrogen and creatinine and ratio of urinary microalbumin to creatinine in serum， the contents of MDA and 8-OHdG and the protein expressions of TGF-β

， Fn and Col Ⅳ were increased significantly in model group （

＜0.05）， while the contents of SOD， GSH-Px and the protein expressions of p-Akt， Nrf2， HO-1 in renal tissue were decreased significantly （

＜0.05）； the significant thickening of the basement membrane， accumulation of mesangial matrix， glomerulosclerosis and interstitial fibrosis of the renal tubules were all found. Compared with model group， above indexes of mice were all reversed significantly in TAB groups （

＜0.05）， and pathological changes were alleviated in a dose-dependent manner.

CONCLUSIONS

TAB can improve blood glucose metabolism and kidney function and alleviate renal tubulointerstitial fibrosis in DN model mice， the mechanism of which may be associated with activating the Akt/Nrf2/HO-1 signaling pathway and suppressing ECM deposition.

关键词

紫丹酸B糖尿病肾病氧化应激纤维化Akt/Nrf2/HO-1信号通路

Keywords

diabetic nephropathyoxidative stressfibrosisAkt/Nrf2/HO-1 signaling pathway

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