AMPK自噬信号通路在藏药四味黄芪散干预低氧性肺动脉高压中的变化特点  

Changes of AMPK autophagy signaling pathway in the intervention of Tibetan medicine Tibetan medicine Siweihuangqi powder on hypoxic pulmonary hypertension

作　　者：李清月 姜欣宇 李生花 靳国恩[3] Li Qingyue;Jiang Xinyu;Li Shenghua;Jin Guoen(Medical Department of Qinghai University Department of Basic Medicine,Xining 810001,China;Medical Department of Qinghai University College of Clinical Medicine,Xining 810001,China;Medical Department of Qinghai University Research Center for High Altitude Medicine,Xining 810001,China)

机构地区：[1]青海大学医学部基础医学部,青海西宁810001 [2]青海大学医学部临床医学院,青海西宁810001 [3]青海大学医学部高原医学研究中心,青海西宁810001

出　　处：《中国高原医学与生物学杂志》2023年第2期73-80,共8页Journal of Chinese High Altitude Medicine & Biology

基　　金：青海省科技厅应用基础研究项目(2018-ZJ-761)。

摘　　要：目的研究AMPK自噬信号通路在藏药四味黄芪散干预低氧性肺动脉高压(HPH)中的变化特点,探究自噬活动是否参与低氧性肺动脉高压的形成。方法将130只大鼠(雄性Wistar)随机分为常氧对照组、低氧对照组、低氧四味黄芪散组和低氧红景天组。将作为常氧对照组的10只大鼠暴露于2260 m海拔环境(室内)饲养并测定相关指标;另三组大鼠置于低压氧舱(模拟5000 m海拔),每组再根据暴露低压低氧时间又分为1、7、15、30 d组,每组10只,测定各时间点相关指标。测定指标包括平均肺动脉压(mPAP)、右心肥厚指数[RV/(LV+S)]和eNOS、ET-1、AMPK、ULK1、Bcl-2、Beclin1、LC3蛋白表达水平。结果低氧四味黄芪散组和低氧红景天组mPAP和RV/(LV+S)均降低(P<0.05)。低氧四味黄芪散组eNOS、AMPK于后期升高,前期ET-1、ULK1和Beclin1低于低氧红景天组(P<0.05),后期高于低氧红景天组(P<0.05),前期Bcl-2高于低氧红景天组(P<0.05),后期低于低氧红景天组(P<0.05),LC3高于低氧红景天组(P<0.05)。结论1.藏药四味黄芪散和红景天均能减缓低氧性肺动脉压的升高和右心室增厚,其作用与上调eNOS和下调ET-1水平有关,前者略优于后者。2.低氧能上调AMPK的表达,藏药四味黄芪散和红景天均能影响ULK1的自噬活动,藏药四味黄芪散可激活低氧后期的自噬活动,而红景天可影响低氧早期的自噬活动。Objective To investigate the changes of AMPK autophagy signaling pathway in the intervention of Tibetan medicine Siweihuangqi powder on hypoxic pulmonary hypertension(HPH),and to explore whether autophagy is involved in the formation of HPH.Methods 130 male Wistar rats were randomly divided into control group,hypoxic control group,hypoxic Siweihuangqi powder group and hypoxic Rhodiola group.Ten rats as control group were exposed to 2260 m altitude(indoor),and the related indexes were measured.The rats in the other three groups were placed in hypobaric oxygen chamber(simulated alitude of 5000 m).Each group was divided into 1,7,15 and 30-day groups according to the time of exposure to hypobaric hypoxic,with 10 rats in each group.The mean pulmonary arterial pressure(mPAP),right ventricular hypertrophy index[RV/(LV+S)]and protein expression levels of eNOS,ET-1,AMPK,ULK1,Bcl-2,Beclinl,LC3 were measured.Results mPAP and RV/(LV+S)were decreased in both drug groups(P<0.05).In the hypoxic Siweihuangqi powder group,eNOS and AMPK increased in the late stage;ET-1,ULK1 and Beclinl were lower in the early stage than those in the hypoxic Rhodiola group(P<0.05),higher in the late stage than those in the hypoxic Rhodiola group(P<0.05);Bcl-2 was higher in the early stage than that in the hypoxic Rhodiola group(P<0.05),lower in the late stage than that in the hypoxic Rhodiola group(P<0.05),and LC3 was higher than that in hypoxic Rhodiola group(P<0.05).Conclusion 1.Both Tibetan medicine Siweihuangqi powder and Rhodiola could slow down the increase of hypoxic pulmonary artery pressure and right ventricular hypertrophy,which was related to the up-regulation of eNOS and down-regulation of ET-1.Tibetan medicine Siweihuangqi powder was slightly better than Rhodiola.2.Hypoxic could up-regulate the expression of AMPK.Tibetan medicine Siweihuangqi powder and Rhodiola could affect the activity of ULKI autophagy.Tibetan medicine Siweihuangqi powder could activate autophagy activity in the later period of hypoxic,while Rhodiola could affect au

关 键 词：藏药 四味黄芪散 红景天 低氧性肺动脉高压 自噬信号 

分 类 号：R5[医药卫生—内科学]