天麻素对帕金森氏症模型大鼠mTOR/HIF-1α通路、糖酵解代谢的影响

Effects of gastrodin on mTOR/HIF-1αpathway and glycolytic metabolism in Parkinson's disease model rats

目的探讨天麻素对帕金森氏症模型大鼠mTOR/HIF-1α通路、糖酵解代谢的影响。方法40只雄性SD大鼠随机分为正常对照组、模型组、天麻素低剂量组、高剂量组,每组10只。模型组、天麻素低剂量组、高剂量组均进行中脑黑质致密部(substantia nigra pars compacta,SNc)注射脂多糖(LPS)以建立PD模型,天麻素低剂量组、高剂量组给予10、50 mg/kg天麻素水溶液腹腔注射,持续9 d。旷场实验、网格测试检测行为学变化,western blot检测p-mTOR、HIF-1α、IL-1β表达,免疫荧光检测酪氨酸羟化酶(TH)、IBA1、HIF-1α表达,HK活性、乳酸含量检测糖酵解代谢情况。结果与正常对照组相比,模型组动物在旷场中央区域停留时间比例下降(P<0.01),网格上逃避潜伏期延长(P<0.01),SNc脑区TH表达明显下降(P<0.01),己糖激酶(HK)活性、乳酸含量上升(P<0.01),IBA1、IL-1β、p-mTOR、HIF-1α表达明显上升(P<0.01);与模型组相比,天麻素低剂量组、高剂量组动物在旷场中央区域停留时间比例上升(P<0.05或P<0.01),网格逃避潜伏期均缩短(P<0.01),SNc脑区TH表达上升(P<0.01),HK活性、乳酸含量下降(P<0.05或P<0.01),IBA1、IL-1β、p-mTOR、HIF-1α表达下降(P<0.05或P<0.01)。结论天麻素干预可能调节小胶质细胞,通过调节mTOR/HIF-1α通路、糖酵解代谢,抑制TH+神经元丢失,从而改善PD大鼠神经行为学损伤。

Objective To investigate the effects of gastrodin on mTOR/HIF-1αpathway and glycolytic metabolism in Parkin⁃son's disease model rats.Methods 40 male SD rats were randomly divided into normal control group,model group,gastrodin low-dose group and high-dose group,with 10 rats in each group.The model group,gastrodin low-dose group,and high-dose group were all injected with LPS into the substantia nigra pars compacta(SNc)to establish a PD model.10,50 mg/kg/d gastrodin aqueous solution was injected intraperitoneally for 9 days.Open field test and grid test to detect behavioral changes,western blot to detect p-mTOR,HIF-1α,IL-1βexpression,immunofluorescence to detect Tyrosine Hydroxylase(TH),IBA1,HIF-1αexpression,hexokinase(HK)activity and lactic acid content to detect glycolytic metabolism.Results Compared with the normal control group,the proportion of animals staying in the central area of the open field decreased in the model group(P<0.01),the escape latency on the grid was prolonged(P<0.01),and the expression of TH in the SNc brain area was sig⁃nificantly decreased(P<0.01),HK activity,lactic acid content increased(P<0.01),IBA1,IL-1β,p-mTOR,HIF-1αexpression significantly increased(P<0.01);compared with the model group,the proportion of animals staying in the central ar⁃ea of open field increased in gastrodin low-dose group,high-dose group(P<0.05 or P<0.01),grid escape latency was shortened(P<0.01),TH expression in SNc brain area increased(P<0.01),HK activity,lactic acid content decreased(P<0.05 or P<0.01),and the expressions of IBA1,IL-1β,p-mTOR,and HIF-1αdecreased(P<0.05 or P<0.01).Con⁃clusion Gastrodin intervention may target microglia,and reduce the loss of TH+neurons by inhibiting the mTOR/HIF-1αpathway and glycolytic metabolism,thereby improving neurobehavioral damage in PD rats.