Sun Qian, Meng Qing-tao, Jiang Ying, Liu Hui-min, Lei Shao-qing, Su Wa-ting, Duan Wei-na, Wu Yang, Xia Zheng-yuan, Xia Zhong-yuan
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
PLoS One. 2013 Dec 4;8(12):e80859. doi: 10.1371/journal.pone.0080859. eCollection 2013.
Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway.
人参皂苷Rb1（RB1）是人参中临床疗效最为显著的成分，具有多种生物活性。本研究旨在探讨RB1对小鼠肠缺血再灌注（IIR）诱导的肾损伤的保护作用及其潜在机制。在通过阻断肠系膜上动脉45分钟，然后再灌注120分钟诱导IIR之前给予RB1。全反式维甲酸（ATRA）用作NF-E2相关因子2（Nrf2）信号通路的抑制剂。成年雄性C57BL/6J小鼠随机分为六组：（1）假手术组，（2）IIR组，（3）RB1组，（4）假手术+ATRA组，（5）IIR+ATRA组，和（6）RB1+ATRA组。观察肠道组织学和病理损伤评分。还通过测量血清二胺氧化酶（DAO）评估肠黏膜损伤。IIR诱导的肾损伤表现为组织学严重程度评分、血尿素氮（BUN）、血清肌酐（Scr）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平升高，同时伴有肾TUNEL阳性细胞和Bcl-2/Bax表达比值升高。与IIR组相比，RB1显著减轻了肾损伤和细胞凋亡，而ATRA处理可逆转这种作用。免疫组织化学和蛋白质印迹分析表明，RB1显著上调血红素加氧酶-1（HO-1）和Nrf2的蛋白表达，而ATRA处理可使其减弱。综上所述，这些结果表明RB1预处理对IIR诱导的肾损伤的保护作用与Nrf2/抗氧化反应元件（ARE）通路的激活有关。
