Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion-induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway
Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion-induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway
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DOI：
10.3892/mmr.2019.10018
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
Liu, Dezhao
中科院分区：
文献类型：
--
作者：
Chen, Sufang;Li, Xiang;Liu, Dezhao
人参皂苷Rb 1（Ginsenoside Rb 1，GRb 1）是从人参中分离的主要活性皂苷之一，近年来有研究表明其具有保护多种器官免受缺血/再灌注（IR）损伤的作用，但其在肠IR（IIR）后的保护作用机制尚不清楚。本研究旨在评估GRb 1对IIR损伤的影响并确定这些影响的机制。将Sprague道利大鼠进行上级肠系膜动脉闭塞75分钟，随后再灌注3小时。在诱导IIR前1 h腹腔内给予GRb 1（15 mg/kg），伴或不伴静脉内给予渥曼青霉素[WM;一种磷酸肌醇3-激酶（PI 3 K）抑制剂，0.6 mg/kg]。通过组织病理学评价和测定血清D-乳酸、二胺氧化酶和内毒素的活性水平以及丙二醛（MDA）、超氧化物歧化酶（SOD）和8-异前列腺素F-2（8-iso-PGF（2））的水平来确定肠损伤和氧化应激损伤的程度。Western blotting法检测p85、磷酸化p85、蛋白激酶B（Akt）、p-Akt和核因子红细胞2相关因子2（Nrf 2）的蛋白表达水平，ELISA法检测肿瘤坏死因子（TNF-）、白细胞介素（IL）-1和IL-6的浓度。结果表明，IIR导致严重的肠损伤（如通过肠Chiu评分的显著增加所确定的），这伴随着肠粘膜屏障完整性的破坏。肠组织中TNF-α、IL-1、IL-6、MDA和8-iso-PGF（2）的表达增加，SOD的表达降低。GRb 1减少肠道组织损伤，抑制炎症反应和氧化应激。此外，GRb 1的保护作用被WM消除。提示GRb 1可能通过激活PI 3 K/蛋白激酶B/Nrf 2通路减轻IIR损伤。
Ginsenoside Rb1 (GRb1), one of the major active saponins isolated from ginseng, has recently been reported to protect various organs against ischemia/reperfusion (IR) injury; however, the mechanisms underlying these protective effects following intestinal IR (IIR) remain unclear. The present study aimed to evaluate the effects of GRb1 on IIR injury and determine the mechanisms involved in these effects. Sprague Dawley rats were subjected to 75 min of superior mesenteric artery occlusion, followed by 3 h of reperfusion. GRb1 (15 mg/kg) was administered intraperitoneally 1 h prior to the induction of IIR, with or without intravenous administration of Wortmannin [WM; a phosphoinositide 3-kinase (PI3K) inhibitor, 0.6 mg/kg]. The degree of intestinal injury and oxidative stress-induced damage was determined by histopathologic evaluation and measurement of the serum activity levels of D-lactate, diamine oxidase and endotoxin, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and 8-iso-prostaglandin F-2 (8-iso-PGF(2)). The protein expression levels of p85, phosphorylated (p)-p85, protein kinase B (Akt), p-Akt and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined via western blotting, and the concentrations of tumor necrosis factor- (TNF-), interleukin (IL)-1 and IL-6 were measured via ELISA. It was revealed that IIR led to severe intestinal injury (as determined by significant increases in intestinal Chiu scores), which was accompanied with disruptions in the integrity of the intestinal mucosal barrier. IIR also increased the expression levels of TNF-, IL-1, IL-6, MDA and 8-iso-PGF(2) in the intestine, and decreased those of SOD. GRb1 reduced intestinal histological injury, and suppressed inflammatory responses and oxidative stress. Additionally, the protective effects of GRb1 were eliminated by WM. These findings indicated that GRb1 may ameliorate IIR injury by activating the PI3K/protein kinase B/Nrf2 pathway.