模拟急性高原缺氧对小鼠一氧化氮相关通路的影响  

Effect of Simulated Acute High Altitude Hypoxia on Nitric Oxide-related Pathways in Mice

作　　者：张淼[1] 魏冠平 黄煜 何庆[1,2] ZHANG Miao;WEI Guanping;HUANG Yu;HE Qing(Medical School of Southwest Jiaotong University,Chengdu 610031,Sichuan,China;The Affiliated Hospital of Southwest Jiaotong University,The Third People's Hospital of Chengdu,Chengdu 610031,Sichuan,China)

机构地区：[1]西南交通大学医学院,四川成都610031 [2]西南交通大学附属医院成都市第三人民医院,四川成都610031

出　　处：《心血管病学进展》2020年第9期984-988,共5页Advances in Cardiovascular Diseases

基　　金：国家自然科学基金(81501640)。

摘　　要：目的研究急性高原缺氧对小鼠一氧化氮(NO)相关通路的影响,并探讨补充L-精氨酸对NO含量的影响。方法将40只小鼠随机分为4组:常氧对照组(N组)、缺氧模型组(M组)、低剂量L-精氨酸组(LL组)和高剂量L-精氨酸组(HL组),每组10只,连续10 d于同一时间点按体重灌胃给药。其中,前3 d于正常环境中给药,N组和M组给予生理盐水。随后,将小鼠置于模拟海拔4000 m的低压低氧动物实验舱中饲养1周。采用酶联免疫吸附剂测定法检测肺组织不对称二甲基精氨酸(ADMA)、内皮型一氧化氮合酶(eNOS)和Ⅰ型精氨酸酶(ARGⅠ)浓度,硝酸还原酶法检测肺组织NO含量。结果与N组小鼠体重增加相比,M组、LL组和HL组小鼠体重减轻(P<0.01,P<0.01,P<0.05),与M组相比,LL组和HL组体重变化无统计学意义。与N组相比,M组、LL组和HL组ADMA浓度显著增加,差异均有统计学意义(P<0.01)。与M组相比,LL组和HL组ADMA浓度明显下降(P<0.01,P<0.01),其中,HL组ADMA浓度<LL组(P<0.01)。M组NO含量>N组、LL组和HL组,但差异均无统计学意义。与N组相比,M组eNOS和ARGⅠ的浓度明显增加(P<0.05,P<0.01)。M组eNOS浓度>LL组(P<0.01)。与M组相比,LL组和HL组的ARGⅠ浓度降低,LL组ARGⅠ浓度<HL组(P<0.01)。M组和HL组ARGⅠ/e NOS>LL组(P<0.01,P<0.01)。结论急性高原缺氧会导致NO相关通路失衡,其可能机制为ADMA对eNOS的竞争性抑制作用和eNOS与ARGⅠ之间的相互竞争,补充L-精氨酸不能增加NO含量。Objective To study the effect of acute high altitude hypoxia on nitric oxide(NO)-related pathway in mice,and explore the effect of L-arginine supplementation on NO level.Methods A total of 40 mice were randomly divided into four groups:normoxic control group(group N),hypoxic model group(group M),low-dose L-arginine group(group LL)and high-dose L-arginine group(group HL),with 10 mice in each group.At the same point for 10 consecutive days,intragastric administration was performed according to body weight.During the first three days,the L-arginine was administered in a normal environment,and the group N and group M were given normal saline simultaneously.Then,the mice were raised in a hypobaric hypoxic animal experimental chamber at a simulated altitude of 4000 m for one week.Concentration of lung tissue asymmetric dimethylarginine(ADMA),endothelial nitric oxide synthase(eNOS)and arginaseⅠ(ARGⅠ)were detected using enzyme-linked immunosorbent assay,and content of NO in lung tissue was detected by nitrate reductase method.Results Mice in group N gained weight,while mice in group M,group LL and group HL lost weight(P<0.01,P<0.01,P<0.05).Compared with group M,the weight change of group LL and HL showed no statistical significance.The ADMA concentration in group M,group LL and group HL was higher than that in group N with statistical significance(P<0.01).Compared with group M,ADMA concentration in group LL and group HL decreased significantly(P<0.01,P<0.01),and it was lower in group HL than that in group LL(P<0.01).The content of NO in group M was higher than that in group N,group LL and group HL,but the difference was not statistically significant.Compared with group N,the concentrations of eNOS and ARG I in group M were significantly increased(P<0.05,P<0.01).The concentration of eNOS in group LL decreased compared with that in group M(P<0.01).Compared with group M,ARGⅠconcentration in group LL and group HL reduced,and it was lower in group LL than in group HL(P<0.01).The ratio of ARGⅠ/eNOS in group M and group

关 键 词：缺氧 一氧化氮 不对称二甲基精氨酸 L-精氨酸 

分 类 号：R339.5[医药卫生—人体生理学]