基于sirt1-FOXO1通路研究松果菊苷对糖尿病肾损伤大鼠的保护作用
Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway
- 上海中医药杂志 2021年55卷第2期 页码：76-81
- 作者机构：
1.黑龙江中医药大学附属第二医院内分泌科（黑龙江 哈尔滨 150001）
2.黑龙江中医药大学附属第二医院检验科（黑龙江 哈尔滨 150001）
- 作者简介：
牛世煜，女，主治医师，主要从事糖尿病及其并发症的基础与临床研究工作
樊蓉，副主任医师；E-mail：rongfan2016@163.com
- 基金信息：黑龙江省自然科学基金项目(H2018059)
DOI：10.16305/j.1007-1334.2021.2004224
中图分类号：
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牛世煜, 叶婷, 于佳远, 等. 基于sirt1-FOXO1通路研究松果菊苷对糖尿病肾损伤大鼠的保护作用[J]. 上海中医药杂志, 2021,55(2):76-81.
Shiyu NIU, Ting YE, Jiayuan YU, et al. Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(2):76-81.
牛世煜, 叶婷, 于佳远, 等. 基于sirt1-FOXO1通路研究松果菊苷对糖尿病肾损伤大鼠的保护作用[J]. 上海中医药杂志, 2021,55(2):76-81. DOI： 10.16305/j.1007-1334.2021.2004224.
Shiyu NIU, Ting YE, Jiayuan YU, et al. Study on protective effect of echinacoside on diabetic rats with renal injury based on sirt1-FOXO1 pathway[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(2):76-81. DOI： 10.16305/j.1007-1334.2021.2004224.
摘要
目的,2,基于沉默信息调节因子1（sirt1）/叉头转录因子1（FOXO1）通路研究松果菊苷对糖尿病肾损伤大鼠的保护作用。,方法,2,建立糖尿病肾损伤大鼠模型，随机分为模型组、松果菊苷组、EX527组（sirt1抑制剂）、松果菊苷-EX527组，每组12只，另取12只SD大鼠设为对照组；分组干预后，采用全自动生化分析仪测定大鼠肾功能指标血清肌酐（Scr）、血尿酸（SUA）、尿微量白蛋白（UMA）水平；采用HE染色检测大鼠肾组织病理形态；采用超氧化物歧化酶（SOD）检测试剂盒及丙二醛（MDA）检测试剂盒分别检测肾组织中SOD、MDA水平；采用酶联免疫吸附试验（ELISA）检测大鼠血清中肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）水平；采用蛋白免疫印迹法检测各组大鼠肾组织sirt1/FOXO1通路相关蛋白表达。,结果,2,与对照组相比，模型组大鼠肾脏可见肾小球体积增大，系膜基质增多，肾小管肿胀、坏死伴空泡样变性，炎性浸润等病理损伤，肾组织SOD含量、sirt1表达降低（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1升高（,P,<,0.01）。与模型组相比，松果菊苷组大鼠肾组织病理损伤减轻，肾组织SOD含量、sirt1表达升高（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1降低（,P,<,0.01）；EX527组大鼠肾组织病理损伤加重，肾组织SOD含量、sirt1表达降低（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1升高（,P,<,0.01）。与松果菊苷组相比，松果菊苷-EX527组大鼠肾组织病理损伤加重，肾组织SOD含量、sirt1表达降低（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1升高（,P,<,0.01）。与EX527组比较，松果菊苷-EX527组大鼠肾组织病理损伤减轻，肾组织SOD含量、sirt1表达升高（,P,<,0.01），Scr、SUA、UMA、血清TNF-α及IL-6水平、肾组织MDA含量、acely-FOXO1/FOXO1降低（,P,<,0.01）。,结论,2,松果菊苷可能通过激活sirt1/FOXO1通路，抑制氧化应激及炎症反应发生，减轻糖尿病肾损伤。
Abstract
Objective,2,To study the protective effect of echinacoside on diabetic rats with renal injury by sirt1/FOXO1 pathway.,Methods,2,Diabetic renal injury rats were randomly divided into three groups: model group, echinacoside, EX527, and echinacoside-EX527 with 12 rats in each group. Other 12 SD rats were selected as the control group. Furthermore, serum creatinine (Scr) , serum uric acid (SUA) and urinary microalbumin (UMA) were measured by automatic biochemical analyzer. HE staining was used to detect the pathological morphology of renal tissue. Superoxide dismutase (SOD) test kit and malondialdehyde (MDA) test kit were used to detect the levels of SOD and MDA in renal tissue. The levels of tumornecrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum of rats were detected by enzyme-linked immunosorbent assay (ELISA) . The expression of sirt1/FOXO1 pathway related protein was detected by Western blot.,Results,2,Compared with the control group, the renal glomerulus volume and mesangial matrix of rats in the model group were increased, and the renal tubules were swollen and necrotic with vacuolized degeneration and inflammatory infiltration. In addition, the content of SOD and the expression of sirt1 in renal tissue decreased (,P,<,0.01) , while Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were all increased (,P,<,0.01) . Compared with the model group, the pathological damage of renal tissue in the echinacoside group was reduced, and the content of SOD and the expression of sirt1 in renal tissue increased (,P,<,0.01) . Besides, Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were decreased (,P,<,0.01) . In the EX527 group, the pathological damage of renal tissue was aggravated, and the content of SOD and the expression of sirt1 in renal tissue decreased (,P,<,0.01) . Moreover, Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were increased (,P,<,0.01) . Compared with the echinacoside group, the renal pathological damage of the echinacoside-EX527 group was aggravated. The content of SOD and the expression of sirt1 in renal tissue decreased (,P,<,0.01) . Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 were increased (,P,<,0.01) . Compared with EX527 group, the pathological damage of kidney tissue of rats in echinacoside-EX527 group was alleviated, and the content of SOD and the expression of sirt1 in renal tissue were increased (,P,<,0.01) . Additionally, Scr, SUA, UMA, levels of serum TNF-α and IL-6, content of MDA in renal tissue and acely FOXO1/FOXO1 decreased (,P,<,0.01) .,Conclusion,2,Echinacoside may inhibit oxidative stress and inflammation by activating the sirt1/FOXO1 pathway to reduce diabetic renal injury.
关键词
松果菊苷糖尿病肾损伤sirt1/FOXO1通路大鼠
Keywords
echinacosidediabetes mellitusrenal injurysirt1/FOXO1 pathwayrat
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