藓生马先蒿苯乙醇苷对高原记忆损伤的改善作用及机制研究

Amelioration Effect and Mechanisms of Phenylethanoid Glycosides from Pedicularis muscicola Maxim on High Altitude Memory Impairment

目的探讨藓生马先蒿苯乙醇苷(phenylethanoid glycosides,Ph Gs)对高原记忆损伤的改善作用及机制。方法八臂迷宫训练成功的清洁级Wistar大鼠50只,随机分为常氧对照组、缺氧组、苯乙醇苷50、200、400 mg·kg^(-1)剂量组(分别给予相应的剂量),常氧对照组和缺氧组给予等体积的蒸馏水,连续给药1周。给药第4天,缺氧组和苯乙醇苷50、200、400 mg·kg^(-1)剂量组置于大型低压氧舱模拟高原低压低氧环境(7 500 m,3 d)。八臂迷宫测定空间记忆能力,HE染色观察大鼠脑组织形态学改变,生化测定血浆和脑组织中丙二醛(MDA)、活性氧(ROS)含量和还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)活力。结果与常氧对照组比较,缺氧组工作记忆错误(WME)、参考记忆错误(RWE)及总记忆错误(TE)分别增加800%,71%和127.1%(P<0.01),脑组织神经元损伤明显增加,血浆和脑组织中还原型谷胱甘肽、超氧化物歧化酶酶活力分别降低60.9%和18.11%(P<0.05,P<0.01),脑组织中丙二醛含量增加74.8%(P<0.01)。与缺氧组比较,苯乙醇苷200、400 mg·kg^(-1)剂量组工作记忆错误、参考记忆错误及总记忆错误分别降低68.44%,63.11%;33.14%,25.34%以及43.91%,36.72%(P<0.05,P<0.01);脑组织神经元损伤明显减轻;血浆及脑组织中还原型谷胱甘肽酶活力分别升高219.76%,180.75%和32.81%,24.10%(P<0.05,P<0.01);超氧化物歧化酶酶活力分别升高19.57%,13.88%和15.41%,15.45%(P<0.05);血浆中丙二醛含量分别降低42.73%,41.87%(P<0.01);脑组织中丙二醛、活性氧含量分别降低61.71%,42.79%和40.76%,23.53%(P<0.01);苯乙醇苷50 mg·kg^(-1)剂量组相应指标有所改善,但差异无显著性。结论藓生马先蒿苯乙醇苷对高原记忆损伤有改善作用,可能与其抗氧化应激和抑制细胞损伤有关。

OBJECTIVE To investigate the ameliorated effect and mechanisms of phenylethanoid glycosides from Pedicularis musci- cola Maxim on high altitude memory impairment. METHODS After successfully trained in the 8-arms radial maze, fifty Wistar rats were randomly divided into normoxic control group, hypoxia group, phenylethanoid glycosides 50, 200 and 400 mg · kg- l groups （ given corresponding dose）. Normoxic control and hypoxia groups were administered with distilled water for a week. When drug delivery in the fourth day, hypoxia and phenylethanoid glycosides groups rats were exposed to a simulated of 7 500 m in a specially designed animal de- compression chamber. Eight arms radial maze was used to measure spatial memory, HE stained was used to observe the cell morphology in brain tissue and biochemical technique was used to detect the content of MDA and ROS and enzymatic activity of GSH and SOD in brain tissue and serum. RESULTS Compared with the normoxic control group, for hypoxia group rats, WME, RWE and TE were re- spectively increased by 800%, 71%, and 127. 1% （P 〈0. 01 ） and neuron damage was significantly increased, the enzymatic activity of GSH and SOD were respectively decreased by 60. 9% and 18. 11% （P 〈 0. 05, P 〈 0. 01 ） in brain tissue and plasma while the content of MDA was increased in brain tissueby 74. 8% （P 〈 0. 01 ）. Compared with the hypoxia group, for phenylethanoid glycosides 200, 400 mg · kg-1 groups rats, WME, RWE, TE were respectively decreased by 68.44%, 63.11% ; 33.14%, 25. 34% and 43.91%, 36. 72% （P 〈0. 05, P 〈0. 01 ） and neuron damage was significantly decreased, the enzymatic activity of GSH were respectively increased by 219.76%, 180. 75% and 32. 81%, 24. 10% （P 〈0. 05, P 〈0. 01 ） and the enzymatic activity of SOD were respectively increased by 9. 57%, 13.88% and 15.41%, 15.45% （P 〈0. 05） in brain tissue and plasma,while the content of MDA in plasma were respectively decreased by 42. 73% , 42. 73% （ P 〈0.01 ） and MDA and ROS in brain tissue were respectively decreased by 61.71% , 42. 79% and 40. 76%, 23.53% （P 〈 0. 01 ） ; for phenylethanoid glycosides 50 mg · kg-1 group rats, the corresponding indicators had been ameliora- ted, but there was no significant difference. CONCLUSION Phenylethanoid glycosides of Pedicnlaris muscicola Maxim can ameliorate high altitude memory impairment, which its involved mechanism may be antioxidant stress and inhibition on cell damage.