藏药四味黄芪散通过AMPK蛋白诱导的自噬信号通路干预低氧性肺动脉高压的研究  

The intervention effect of Tibetan medicine Siwei Huangqi powder on hypoxic pulmonary hypertension through autophagy signaling pathway induced by AMPK protein

作　　者：李生花[1] 杨全余[1,2,3] 嘎琴 靳国恩[1,2,3] LI Sheng-hua;YANG Quan-yu;GA Qin;JIN Guo-en(Medical College of Qinghai University;Qinghai Province Key Lab of Applied Foundation for High Altitude Medicine(Qinghai-Utah Joint Research Lab for High Altitude Medicine);Key Lab for High Altitude Medicine,Ministry of Education,Xining 810001,China)

机构地区：[1]青海大学医学院 [2]青海省高原医学应用基础重点实验室(青海-犹他高原医学联合重点实验室) [3]教育部高原医学重点实验室,青海西宁810001

出　　处：《中国药理学通报》2023年第1期178-184,共7页Chinese Pharmacological Bulletin

基　　金：青海省科技厅应用基础研究项目(No2018-ZJ-761);国家自然科学基金资助项目(No81550040)。

摘　　要：目的探讨藏药四味黄芪散(SW)降低低氧性肺动脉高压的作用机制。方法将110只SD大鼠随机分为常氧组、低氧对照组和低氧药物组,两低氧组根据暴露低氧时间又各分为d 1、3、7、15、30组,共10个小组。常氧组置于海拔2260 m的大气环境,不予干预;低氧10个组置于模拟海拔5000 m的低压氧舱,低氧药物组给予SW混悬液(0.42 g/100 g)灌胃,低氧对照组给予生理盐水灌胃,每天1次。每组大鼠于相应时间点测定Ppa、RV/(LV+S);Western blot法测定肺组织p-AMPK、ULK-1、LC3Ⅰ/LC3Ⅱ蛋白水平。结果与常氧组相比,低氧对照组大鼠Ppa、RV/(LV+S)比值随暴露低氧时间的延长逐渐增高,并与肺动脉平滑肌层厚度和肺组织亚细胞器变化保持一致。肺组织p-AMPK蛋白表达水平也轻度上调(P<0.05),ULK-1、LC3Ⅱ明显上调(P<0.01),尤以急性低氧期变化明显;与低氧对照组相比,低氧药物组Ppa升高幅度和肺动脉平滑肌层增厚程度明显减缓(P<0.05~0.01),而肺组织中p-AMPK、ULK-1、LC3Ⅱ蛋白表达水平随暴露低氧时间的延长而进一步增高(P<0.05~0.001),尤以慢性低氧为甚。结论SW可通过上调AMPK自噬信号通路发挥抑制低氧性肺动脉高压的作用。Aim To explore the mechanism of Tibetan medicine Siwei Huangqi powder(SW)in reducing hypoxic pulmonary hypertension.Methods A total of 110 Wistar rats were randomly divided into normoxia control group,hypoxic control group and hypoxic drug group.The two hypoxic groups were divided into 1,3,7,15 and 30 day group according to the exposure time of hypoxic,10 groups in total.The normoxia control group was placed in the atmospheric environment at an altitude of 2260 meters without intervention;10 hypoxic groups were placed in a hypobaric hypoxic chamber with a simulated altitude of 5000 meters.The hypoxic drug group was given SW suspension(0.42 g/100 g)by gavage,and the hypoxic control group was given normal saline by gavage,once a day.The Ppa and RV/(LV+S)were measured at the corresponding time points in each group;the levels of p-AMPK,ULK-1 and LC3Ⅰ/LC3Ⅱprotein in lung tissues were measured by WB method.Results Compared with normoxia control group,the ratio of PA and RV/(LV+s)in hypoxic control group increased gradually with the extension of hypoxic exposure time,which was consistent with the thickness of pulmonary artery smooth muscle layer and the changes of pulmonary tissue subcellular organelles.The expression level of p-AMPK protein in lung tissues was also slightly up-regulated(P<0.05),and ULK-1 and LC3Ⅱwere significantly up-regulated(P<0.01),especially in acute hypoxic.Compared with the hypoxic control group,the increase of Ppa and the thickening of pulmonary artery smooth muscle layer in the hypoxic drug group were significantly reduced(P<0.05~0.01),while the expression levels of p-AMPK,ULK-1 and LC3Ⅱproteins in lung tissues increased with the extension of hypoxic exposure time(P<0.05~0.001),especially in chronic hypoxic.Conclusion SW can inhibit hypoxic pulmonary hypertension by up-regulating AMPK autophagy signaling pathway.

关 键 词：藏药四味黄芪散 干预 AMPK 自噬信号通路 低氧 肺动脉高压 

分 类 号：R-332[医药卫生] R282.71R322.35R392R544R845.22