Paeonol Ameliorates Diabetic Renal Fibrosis Through Promoting the Activation of the Nrf2/ARE Pathway via Up-Regulating Sirt1.
Paeonol Ameliorates Diabetic Renal Fibrosis Through Promoting the Activation of the Nrf2/ARE Pathway via Up-Regulating Sirt1.
复制标题
丹皮酚通过上调 Sirt1 促进 Nrf2/ARE 通路的激活，从而改善糖尿病肾纤维化
DOI：
10.3389/fphar.2018.00512
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Zhang L;Chen Z;Gong W;Zou Y;Xu F;Chen L;Huang H
糖尿病肾病（DN）正迅速成为全球终末期肾病的主要原因，也是糖尿病患者发病率和死亡率的主要原因。DN的主要病理改变是肾纤维化。丹皮酚（PA）是从厚朴根皮中提取的单一酚类化合物，具有多种潜在的药理活性。然而，PA对DN的影响尚未完全阐明。本研究以高糖（HG）处理的肾小球系膜细胞（GMCs）和链脲佐菌素（STZ）诱导的糖尿病小鼠为研究对象，探讨PA对DN的作用机制。体外结果表明：（1）PA抑制HG诱导的FN和ICAM-1的过度表达;（2）PA通过激活Nrf 2/ARE通路发挥肾保护作用;（3）Sirt 1介导PA对Nrf 2/ARE通路的激活。与模型组比较，PA治疗组大鼠肾脏中Sirt 1、Nrf 2及其下游相关蛋白的表达水平明显升高。综上所述，我们的研究表明PA延缓糖尿病肾纤维化的进展，其潜在机制可能与调节Nrf 2通路有关。PA对Nrf 2的作用至少部分依赖于Sirt 1的激活。
Diabetic nephropathy (DN) is rapidly becoming the leading cause of end-stage renal disease worldwide and a major cause of morbidity and mortality in patients of diabetes. The main pathological change of DN is renal fibrosis. Paeonol (PA), a single phenolic compound extracted from the root bark of Cortex Moutan, has been demonstrated to have many potential pharmacological activities. However, the effects of PA on DN have not been fully elucidated. In this study, high glucose (HG)-treated glomerular mesangial cells (GMCs) and streptozotocin (STZ)-induced diabetic mice were analyzed in exploring the potential mechanisms of PA on DN. Results in vitro showed that: (1) PA inhibited HG-induced fibronectin (FN) and ICAM-1 overexpressions; (2) PA exerted renoprotective effect through activating the Nrf2/ARE pathway; (3) Sirt1 mediated the effects of PA on the activation of Nrf2/ARE pathway. What is more, in accordance with the in vitro results, significant elevated levels of Sirt1, Nrf2 and downstream proteins related to Nrf2 were observed in the kidneys of PA treatment group compared with model group. Taken together, our study shows that PA delays the progression of diabetic renal fibrosis, and the underlying mechanism is probably associated with regulating the Nrf2 pathway. The effect of PA on Nrf2 is at least partially dependent on Sirt1 activation.
登录
查看更多内容
影响因子：
5.6
作者：
Catino S;Paciello F;Miceli F;Rolesi R;Troiani D;Calabrese V;Santangelo R;Mancuso C
通讯作者：
Mancuso C
影响因子：
2.1
作者：
Chong ZZ;Maiese K
通讯作者：
Maiese K
蛋白激酶CK2α催化亚基通过NF-κB信号通路改善糖尿病肾炎症纤维化
影响因子：
5.8
作者：
Huang, Junying;Chen, Zhiquan;Huang, Heqing
通讯作者：
Huang, Heqing
DOI：
10.1248/yakushi1947.89.9_1205
发表时间：
1969-01-01
影响因子：
0.3
作者：
HARADA, M;YAMASHITA, A
通讯作者：
YAMASHITA, A
影响因子：
5.4
作者：
Ding, Ying-Wei;Zhao, Guang-Ju;Lu, Zhong-Qiu
通讯作者：
Lu, Zhong-Qiu