隔物灸调控缺氧诱导因子-1α表达抑制慢性萎缩性胃炎大鼠糖酵解的机制研究  

Mechanism of Indirect Moxibustion in Inhibition of Glycolysis in Rats with Chronic Atrophic Gastritis by Regulating HIF-1αExpression

作　　者：李琪[1] 吴梦蝶 刘世敏[2] 萧有智 王文佳 马喆[2] 黄艳[2] 李灵杰 李璟[1] 刘慧荣[1,2] LI Qi;WU Mengdie;LIU Shimin;XIAO Youzhi;WANG Wenjia;MA Zhe;HUANG Yan;LI Lingjie;LI Jing;LIU Huirong(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Shanghai Research Institute of Acupuncture and Meridian,Shanghai 200030,China;Shanghai Xinqidian Rehabilitation Hospital,Shanghai 201107,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海市针灸经络研究所,上海200030 [3]上海新起点康复医院,上海201107

出　　处：《世界中医药》2022年第3期323-328,共6页World Chinese Medicine

基　　金：国家自然科学基金面上项目(81674071);国家中医药领军人才支持计划“岐黄学者”;上海市卫生健康委员会科研课题计划资助(20214Y0115);上海市重点专科(针灸)建设(shslczdzk04701)。

摘　　要：目的:观察慢性萎缩性胃炎(CAG)大鼠胃黏膜组织缺氧诱导因子-1α(HIF-1α)及糖酵解关键酶表达变化,探究隔物灸对CAG的作用及可能机制。方法:将雄性Wistar大鼠随机分为正常组和造模组,自由饮用170 mg/L浓度MNNG联合法进行CAG大鼠造模。鉴定模型成功后,造模组大鼠随机分为模型组、隔药饼灸组、隔姜灸组和西药组,每组6只。隔药饼灸组、隔姜灸组均取中脘、气海穴进行隔物灸干预,西药组给予叶酸悬浊液灌胃。采用HE染色法观察胃窦组织病理学变化,实时荧光定量PCR(RT-qPCR)法检测胃黏膜组织信号转导及转录激活因子3(STAT3)、丙酮酸激酶M2(PKM2)和HIF-1α的mRNA表达水平,免疫组织化学法检测胃黏膜组织STAT3、HIF-1α蛋白表达,比色法和ELISA法测定胃黏膜组织LDH、PKM2活性。结果:与正常组比较,模型组大鼠胃黏膜组织固有腺体结构紊乱,腺体减少,出现萎缩、肠化、假幽门腺化生和(或)异型增生。模型组大鼠胃黏膜组织HIF-1α、STAT3、PKM2 mRNA表达上调(P<0.05),STAT3、HIF-1α蛋白表达增加(P<0.05),LDH、PKM2酶活性增加(P<0.05)。与模型组比较,隔药饼灸组、隔姜灸组、西药组固有腺体排列较规整,固有腺体萎缩、肠上皮化生、异型增生程度减轻;隔药饼灸和隔姜灸均能下调大鼠胃黏膜组织中HIF-1α、STAT3 mRNA与蛋白表达(P<0.05),降低LDH、PKM2酶活性(P<0.05)。结论:隔物灸中脘、气海穴可改善CAG大鼠胃窦组织形态学病变,修复胃黏膜损伤。抑制HIF-1α介导的异常糖酵解代谢水平可能是隔物灸法治疗CAG的效应机制之一。Objective:To observe the expression changes of HIF-1α and glycolysis enzymes in gastric mucosa of rats with chronic atrophic gastritis(CAG)and explore the mechanism of indirect moxibustion on CAG.Methods:Male Wistar rats were randomly divided into a normal group and an experimental group.The CAG model was induced in the experimental group by administration of MNNG(170 mg/L).The model rats were then randomly divided into a model group,a herb-partitioned moxibustion(HM)group,a ginger-partitioned moxibustion(GM)group,and a western medicine(WM)group,with six rats in each group.“Zhongwan”(CV 12)and“Qihai”(CV 6)were selected for indirect moxibustion in the HM group and the GM group.The folic acid suspension was administered to the rats in the WM group by gavage.The histopathological changes of gastric antrum were observed by HE staining.The mRNA expression of STAT3,PKM2 and HIF-1αin the gastric mucosa was detected by RT-qPCR,and the protein expression of STAT3 and HIF-1αwas detected by immunohistochemistry.The activities of LDH and PKM2 were determined by colorimetry and ELISA.Results:Compared with the normal group,the model group showed the structural disorder of inherent glands,reduced glands,atrophy,intestinal metaplasia,pseudopyloric metaplasia,and/or dysplasia in the gastric mucosa.Furthermore,the mRNA expression of HIF-1α,STAT3,and PKM2 in the gastric mucosa was up-regulated(P<0.05),the protein expression of STAT3 and HIF-1α was elevated(P<0.05),and the enzyme activities of LDH and PKM2 were potentiated in the model group(P<0.05).Compared with the model group,the HM group,the GM group,and the WM group showed the regular arrangement of inherent glands,and relieved inherent gland atrophy,intestinal metaplasia,and dysplasia.Compared with the model group,the HM group and the GM group displayed down-regulated mRNA and protein expression levels of HIF-1α and STAT3 in the gastric mucosa(P<0.05),and weakened enzyme activities of LDH and PKM2(P<0.05).Conclusion:Indirect moxibustion at“Zhongwan”(CV 12)and

关 键 词：艾灸疗法 隔药饼灸 隔姜灸 慢性萎缩性胃炎 缺氧诱导因子-1Α 糖酵解 

分 类 号：R245.82[医药卫生—针灸推拿学]