Potential therapeutic role of punicalagin against mechanical-trauma-induced stress urinary incontinence via upregulation of Nrf2 and TGF-β1 signaling : Effect of punicalagin on mechanical trauma induced SUI.
Potential therapeutic role of punicalagin against mechanical-trauma-induced stress urinary incontinence via upregulation of Nrf2 and TGF-β1 signaling : Effect of punicalagin on mechanical trauma induced SUI.
复制标题
安石榴苷通过上调 Nrf2 和 TGF-β1 信号传导对机械创伤引起的压力性尿失禁的潜在治疗作用
DOI：
10.1007/s00192-017-3283-x
复制
发表时间：
2017-06
影响因子：
1.8
通讯作者：
Hong L
中科院分区：
文献类型：
--
作者：
Tang J;Liu C;Min J;Hu M;Li Y;Hong L
导言和假设
我们研究了安石榴苷（PUN; 2，3-hexahydroxydiphenoyl-gallagyl-D-glucose）对小鼠机械创伤诱导的压力性尿失禁（SUI）的作用及其机制。
方法
将90只雌性C57 BL/6小鼠随机分为6组：5组进行阴道扩张（VD）1 h，分别于术后第1、3、7、14、28 d（VD组1 d、3 d、7 d、14 d、28 d）测定漏尿点压（LPP）。第六组为非内固定对照（NC）组。然后，将75只处女雌性C57 BL/6小鼠随机分为5组：VD组（仅接受VD）和NC组，每天经口给予生理盐水，持续7天;以及3个VD + PUN组，接受VD，每天分别经口给予PUN 2.5，5和10 mg/kg，持续7天。在第7天检测LPP，然后处死所有小鼠并收获其尿道和阴道前壁用于Masson染色、免疫组织化学研究、Western印迹分析和定量聚合酶链反应（qPCR）。
结果
VD后LPP显著低于NC组，VD后14和28天小鼠的LPP显著高于第1、3和7天。PUN可显著改善VD引起的LPP下降，并减轻VD引起的I型胶原、III型胶原、α-平滑肌肌动蛋白（SMA）、转化生长因子（TGF）-β1、p-Smad 3、核因子-红细胞2型p45相关因子2（Nrf 2）和谷胱甘肽过氧化物酶（GPx 1）蛋白水平的下降以及尿道和阴道前壁8-羟基脱氧鸟苷（OHdG）的增加。PUN还上调锰超氧化物歧化酶（MnSOD）的表达，而Smad 2、p-Smad 2和Smad 3的蛋白水平没有改变。
结论
PUN对机械创伤诱导的小鼠SUI具有一定的治疗作用，其作用可能是通过激活TGF-β1/Smad 3和Nrf 2/抗氧化反应元件（ARE）信号传导激活实现的。
Introduction and hypothesis
We investigated the effect of punicalagin (PUN; 2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), on mechanical-trauma-induced stress urinary incontinence (SUI) in mouse and the mechanisms underlying any effects.
Methods
Ninety virgin female C57BL/6 mice were randomized into six groups: five groups underwent vaginal distention (VD) for 1 h and leak-point pressure (LPP) was measured on the 1st, 3rd, 7th, 14th, and 28th day following (VD groups 1 d, 3 d, 7 d, 14 d, and 28 d). The sixth group was a noninstrumented control (NC) group. Then, 75 virgin female C57BL/6 mice were randomized into five groups: a VD group (that just underwent VD) and an NC group were orally administered saline every day for 7 days; and three VD + PUN groups that underwent VD and were orally administered PUN respectively at 2.5, 5, and 10 mg/kg every day for 7 days. LPP was tested on the day 7, then all mice were sacrificed and their urethras and anterior vaginal walls harvested for Masson staining, immunohistochemistry study, Western blot analysis, and quantitative polymerase chain reaction (qPCR).
Results
LPPs after VD were significantly lower than the NC group, and the LPPs of mice on days 14 and 28 day after VD were significantly higher than on the days 1, 3, and 7. PUN significantly improved VD-induced drops in LPP and alleviated VD-induced decrease of collagen I, collagen III, α-smooth muscle actin (SMA), transforming growth factor (TGF)-β1, and p-Smad3, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), and glutathione peroxidase (GPx1) protein levels, and increase of 8-hydroxydeoxyguanosine (OHdG) in urethra and anterior vaginal wall. PUN also up-regulated the expression of manganese superoxide dismutase (MnSOD), whereas protein levels of Smad 2, p-Smad2, and Smad3 were not changed.
Conclusions
PUN exerts certain therapeutic effect on mechanical-trauma-induced SUI in mice, which might be through the activation of TGF-β1/Smad3 and Nrf2/antioxidant response element (ARE) signaling activation.