Yan Yi-Tian, Li Shu-De, Li Chen, Xiong Yun-Xia, Lu Xue-Hai, Zhou Xin-Fu, Yang Liu-Qing, Pu Li-Jin, Luo Hai-Yun
Department of Pharmacology, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan, PR China.
Department of Biochemistry, College of Basic Medicine, Kunming Medical University, Kunming, Yunnan, PR China.
Behav Brain Res. 2018 Jun 1;345:83-92. doi: 10.1016/j.bbr.2018.02.037. Epub 2018 Mar 6.
Panax notoginsenoside saponins Rb1 (PNS-Rb1) is an important active ingredient of panax notoginseng for effective treatment of cerebrovascular diseases. However, the mechanism underlying its actions in the state of cerebral ischemia is still unclear. We asked whether the potential neuroprotection of PNS-Rb1 on the brain is due to, at least partially, its modulation of AkT/mTOR/PTEN signalling pathway along with down-regulation of caspase-3 in rats subjected to phototrombic stroke. To test this hypothesis, rats with induced photothrombotic stroke were treated with PNS-Rb1 (applied in three different doses, 25 mg/kg, 50 mg/kg,100 mg/kg, respectively) or saline, while sham operated rats injected with saline were used as the control. Our results indicate that PNS-Rb1 significantly alleviated the morphological lesion concomitant with improvement of cognitive and sensorimotor deficits induced by ischemic stroke. Moreover, immunohistochemistry and Western blot analyses showed that PNS Rb1 in a dose dependent manner increased the expressions of P-Akt, P-mTOR and reduced P-PTEN and caspase-3. The present study suggests that the improvement of cognitive and sensorimotor deficits by PNS-Rb1 is made, at least partially, by the modulation of the Akt/mTOR/PTEN signalling pathway.
三七总皂苷Rb1(PNS-Rb1)是三七的一种重要活性成分,对脑血管疾病有显著疗效。然而,其在脑缺血状态下的作用机制尚不清楚。我们探讨了PNS-Rb1对大脑的潜在神经保护作用是否至少部分归因于其对光血栓性脑卒中小鼠Akt/mTOR/PTEN信号通路的调节以及caspase-3表达的下调。为验证这一假设,将光血栓性脑卒中小鼠分为三组,分别给予不同剂量(25mg/kg、50mg/kg、100mg/kg)的PNS-Rb1或生理盐水,假手术组小鼠注射生理盐水作为对照。结果表明,PNS-Rb1能显著减轻缺血性脑卒中引起的形态学损伤,并改善认知和感觉运动功能障碍。此外,免疫组化和蛋白质印迹分析显示,PNS-Rb1能剂量依赖性地增加P-Akt、P-mTOR的表达,并降低P-PTEN和caspase-3的表达。本研究提示,PNS-Rb1对认知和感觉运动功能障碍的改善作用至少部分是通过调节Akt/mTOR/PTEN信号通路实现的。