Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2 Fuxue Lane, Wenzhou 325000, Zhejiang Province, China.
Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
Eur J Pharmacol. 2014 Oct 5;740:480-7. doi: 10.1016/j.ejphar.2014.06.040. Epub 2014 Jun 27.
Ginsenoside Rb1 is reported to possess anti-fatigue activity, but the mechanisms remain unknown. The aim of this study was to investigate the molecular mechanisms responsible for the anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection (MSIR) in aged rat. Aged rats with MSIR were administrated with ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Rats without MSIR but going through the same surgery procedure were administrated with saline as blank controls. Anti-fatigue effect was assessed by an open field test; superoxide dismutase, reactive oxygen species and malondialdehyde in skeletal muscle were determined. The mRNA levels of Akt2 and Nrf2 in skeletal muscle were measured by real-time quantitative PCR. The activation of Akt and Nrf2 was examined by western blot and immunohistofluorescence. Our results revealed that ginsenoside Rb1 significantly increased the journey and the rearing frequency, decreased the time of rest in aged rats with MSIR. In addition, ginsenoside Rb1 significantly reduced reactive oxygen species and malondialdehyde release and increased the superoxide dismutase activity of skeletal muscle in aged rats with MSIR. Ginsenoside Rb1 also increased the expression of Akt2 and Nrf2 mRNA, up-regulated Akt phosphorylation and Nrf2 nuclear translocation. These findings indicate that ginsenoside Rb1 has an anti-fatigue effect on postoperative fatigue syndrome in aged rat, and the mechanism possibly involves activation of the PI3K/Akt pathway with subsequent Nrf2 nuclear translocation and induction of antioxidant enzymes.
人参皂苷 Rb1 被报道具有抗疲劳活性，但作用机制尚不清楚。本研究旨在探讨人参皂苷 Rb1 对老年大鼠小肠大部分切除术后疲劳综合征（MSIR）的抗疲劳作用的分子机制。将 MSIR 后的老年大鼠每天给予人参皂苷 Rb1（15mg/kg）一次，从手术前 3 天至处死当天，或给予相应的生理盐水作为对照。未进行 MSIR 但经历相同手术过程的大鼠给予生理盐水作为空白对照。通过旷场试验评估抗疲劳效果；测定骨骼肌中超氧化物歧化酶、活性氧和丙二醛。实时定量 PCR 测定骨骼肌中 Akt2 和 Nrf2 的 mRNA 水平。通过 Western blot 和免疫荧光法检测 Akt 和 Nrf2 的激活。结果表明，人参皂苷 Rb1 显著增加了 MSIR 老年大鼠的行进和站立次数，减少了休息时间。此外，人参皂苷 Rb1 还显著降低了 MSIR 老年大鼠骨骼肌中活性氧和丙二醛的释放，增加了超氧化物歧化酶的活性。人参皂苷 Rb1 还增加了 Akt2 和 Nrf2 mRNA 的表达，上调了 Akt 磷酸化和 Nrf2 核转位。这些发现表明，人参皂苷 Rb1 对老年大鼠术后疲劳综合征具有抗疲劳作用，其机制可能涉及 PI3K/Akt 通路的激活，随后 Nrf2 核转位和诱导抗氧化酶。
