刘治娟;邹雨桐;马超超;刘小星;泽吉普赤;田丽萍;李洪雷;侯立安;王丹晨;庞金荣;羊红燕;邱玲;
LIU Zhijuan;ZOU Yutong;MA Chaochao;LIU Xiaoxing;ZEJI Puchi;TIAN Liping;LI Honglei;HOU Li' an;WANG Danchen;PANG Jinrong;YANG Hongyan;QIU Ling;Department of Clinical Laboratory,People' s Hospital of Tibet Autonomous Region;Department of Clinical Laboratory,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medcial College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;Department of Clinical Laboratory,Ngari Prefecture People' s Hospital;Department of

• 1:西藏自治区人民医院检验科
• 2:中国医学科学院北京协和医学院北京协和医院检验科疑难重症及罕见病国家重点实验室
• 3:西藏阿里地区人民医院检验科
• 4:西藏日喀则市桑孜珠区人民医院检验科

摘要(Abstract)：

目的探讨西藏不同海拔地区藏族人群红细胞代谢相关血清学指标特征,并建立各指标的参考区间。方法2016年9月—2018年8月,采用整群抽样法随机抽取西藏阿里地区(海拔Ⅰ,海拔4298～4352 m)、拉萨市和日喀则市(海拔Ⅱ,海拔3670～3835 m)、林芝市(海拔Ⅲ,海拔约2900 m)常住人群为研究对象。采集其血液测定全血细胞计数、血清铁(serum iron, SI)、未饱和铁结合力(unsaturated iron binding capacity, UIBC)、转铁蛋白(transferrin, TRF)、铁蛋白(ferritin, FER)、叶酸(folic acid, FA)、维生素B_(12)(vitamin B_(12),Vit B_(12)),计算转铁蛋白饱和度(transferrin saturation, TSAT)。采用多元线性回归和方差成分分析比较不同性别/年龄/海拔藏族人群各指标差异,采用转换参数法建立各指标的参考区间。结果共纳入藏族人群1128例,其中937例用于参考区间建立。男性SI、TSAT、FER水平显著高于女性,TRF、FA、UIBC显著低于女性(P均<0.001);TRF和UIBC随人群年龄增长而逐渐降低,FER随人群年龄增长而逐渐升高,Vit B_(12)以30～39岁年龄组最高;SI、TSAT、FER和Vit B_(12)随海拔升高而逐渐升高(P均<0.001);TRF、UIBC在海拔Ⅱ人群中最高,海拔Ⅲ人群中最低。各指标参考区间如下:SI在女性中为4.5～35.6μmol/L,男性为10.6～41.1μmol/L;UIBC在女性中为19.9～79.5μmol/L,男性为16.4～63.9μmol/L;TRF为1.90～3.64 g/L;TSAT在女性中为5.3%～58.2%,男性为16.4%～68.8%;FER在海拔Ⅰ、Ⅱ女性中为4.81～953.15μg/L,海拔Ⅲ女性为4.85～459.53μg/L,海拔Ⅰ、Ⅱ男性为50.55～1677.28μg/L,海拔Ⅲ男性为48.68～1239.30μg/L;FA为1.96～9.76μg/L;Vit B_(12)为176.3～1162.3 ng/L。结论西藏不同海拔地区人群红细胞代谢相关指标存在性别/年龄/海拔差异,与平原地区居民存在不同,应针对西藏地区建立其人群特异参考区间。
Objective To explore the characteristics of serological parameters related to erythrocyte metabolism in Tibetans living at different altitudes in Tibet, and to establish the reference intervals of each parameter. Methods The cluster-sampling method was used to randomly select residents from Ngari(altitude Ⅰ, 4298-4352 m), Lhasa and Xigaze(altitudeⅡ, 3670-3835 m), and Nyingchi(altitude Ⅲ, about 2900 m) in Tibet from September 2016 to August 2018. Blood samples were collected for the determination of the whole blood-cell count, serum iron(SI), unsaturated ironbinding capacity(UIBC), transferrin(TRF), ferritin(FER), folic acid(FA), and vitamin B_(12)(Vit B_(12)). Transferrin saturation(TSAT) was calculated. Multiple linear regression and variance component analysis were used to compare the differences in gender, age, and altitude for various laboratory parameters among Tibetan population. The reference intervals of the laboratory parameters were established by the transformed parameter method. Results A total of 1128 Tibetans were included in this study, of which 937 subjects were used to establish the reference intervals. The levels of SI, TSAT and FER in males were significantly higher than those in females(all P<0.001). TRF, FA and UIBC in males were significantly lower than those in females(all P<0.001). TRF and UIBC decreased with age; FER increased with age; the highest Vit B_(12) was in the 30-39 age group; SI, TSAT, FER and Vit B_(12) increased with altitude(all P<0.001); the highest TRF and UIBC were at the altitude Ⅱ and the lowest at the altitude Ⅲ. The reference intervals of each index is shown as follows: 4.5-35.6 μmol/L in females and 10.6-41.1 μmol/L in males for SI; 19.9-79.5 μmol/L in females and 16.4-63.9 μmol/L in males for UIBC; 1.90-3.64 g/L for TRF; 5.3%-58.2% in females and 16.4%-68.8% in males for TSAT; 4.81-953.15 μg/L in females at the altitude Ⅰ and Ⅱ, 4.85-459.53 μg/L in females at the altitude Ⅲ, 50.55-1677.28 μg/L in males at altitude Ⅰ and Ⅱ, and 48.68-1239.30 μg/L in males at altitude Ⅲ for FER; 1.96-9.76 μg/L for FA; 176.3-1162.3 ng/L for Vit B_(12). Conclusions There are gender/age/altitude differences in serological parameters related to erythrocyte metabolism among residents in areas at the high altitude. The distribution is also different from that in plain areas. Therefore, it is necessary to establish specific reference intervals for the population in Tibet.

关键词(KeyWords)： 高海拔;铁代谢;叶酸;维生素B_(12);参考区间
high altitude;iron metabolism;folic acid;vitamin B_(12);reference interval

Abstract:

Keywords:

基金项目(Foundation): 西藏自治区科技计划项目(2016XZ01G20);; 西藏自治区人才资源开发专项资金项目2016;; 西藏自治区自然科学基金资助项目(2015ZR-14-51)~~

作者(Authors): 刘治娟;邹雨桐;马超超;刘小星;泽吉普赤;田丽萍;李洪雷;侯立安;王丹晨;庞金荣;羊红燕;邱玲;
LIU Zhijuan;ZOU Yutong;MA Chaochao;LIU Xiaoxing;ZEJI Puchi;TIAN Liping;LI Honglei;HOU Li' an;WANG Danchen;PANG Jinrong;YANG Hongyan;QIU Ling;Department of Clinical Laboratory,People' s Hospital of Tibet Autonomous Region;Department of Clinical Laboratory,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medcial College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;Department of Clinical Laboratory,Ngari Prefecture People' s Hospital;Department of

参考文献(References)：

• [1] 国胜，陈家言，胡永红，等.西藏自治区居民血糖和血脂状况调查[J].中国慢性病预防与控制，2003,25:42- 45.
• [2] 杨敏，裴晓方.高海拔民族地区健康人群血流变指标基本情况探索[J].现代预防医学，2019,9:1939- 1643.Yang M,Pei XF.Blood rheology characteristics of people in high altitude ethnic areas[J].Xiandai Yufang Yixue,2019,9:1939- 1643.
• [3] 李雪，李文斌，封士兰，等.血红蛋白在高原低氧适应中的机制研究进展[J].浙江大学学报(医学版),2019,48:674- 681.Li X,Li WB,Feng SL,et al.Research progress on mechanism in adaptaion of hemoglobin to plateau hypoxia[J].Zhejiang Daxue Xuebao(Yixueban),2019,48:674- 681.
• [4] 白玛康卓，巴桑次仁，次仁央宗，等.不同海拔地区世居藏族人群高原红细胞增多症患病率的流行病学调查[J].第三军医大学学报，2016,38:220- 225.Baima KI,Basang CR,Ciren YZ,et al.Epidemiological investigation of high altitude polycythemia in native Tibetans dwelling in different altitude area[J].Di-san Junyi Daxue Xuebao,2016,38:220- 225.
• [5] 刘丽军，张玉涛，张致英，等.高原红细胞增多症的研究进展[J].国外医学(医学地理分册),2018,39:93- 97.
• [6] 德吉，祝青，杜逸枚，等.西藏大学学生血色素水平及影响因素分析[J].西藏大学学报(自然科学版),2010,25:21- 26.
• [7] 孙舒瑶，王溯源，孙曾梅，等.西藏高原地区铁过载患者铁调素的水平变化[J].中国实验血液学杂志，2020,28:1406- 1409.Sun SY,Wang SY,Sun ZM,et al.Change of hepcidin in patients with iron overload at the tibet plateau[J].Zhongguo Shiyan Xueyexue Zazhi,2020,28:1406- 1409.
• [8] 中华人民共和国卫生部.WS/T405—2012.血细胞分析参考区间 [S/OL].(2012- 12- 25).https://www.antpedia.com/standard/6610870.html.
• [9] World Health Organization.Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity[S/OL].(2011).https://apps.who.int/iris/handle/10665/85839.
• [10] Zou Y,Li H,Pang J,Liu X,et al.An evaluation of urine and serum iodine status in the population of Tibet,China:No longer an iodine-deficient region[J].Nutrition,2020,82:111033.
• [11] Yamamoto Y,Hosogaya S,Osawa S,et al.Nationwide multicenter study aimed at the establishment of common reference intervals for standardized clinical laboratory tests in Japan[J].Clin Chem Lab Med,2013,51:1663- 1672.
• [12] 谢慎威，陈波，刘秉林，等.不同海拔高原习服汉族与世居藏族的血常规比较研究[J].西南国防医药，2019,29:781- 783.Xie SW,Chen B,Liu BL,et al.Comparison of the routine blood indexes between acclimatized Han population and native Tibetan at different high altitudes[J].Xinan Guofang Yiyao,2019,29:781- 783.
• [13] 索朗片多，孙舒瑶，李明霞，等.高原健康成年男性铁代谢的影响因素分析[J].四川大学学报(医学版),2018,49,137- 139.
• [14] Ferrari AD,Miranda JJ,Gilman RH,et al.Prevalence,Clinical Profile,Iron Status,and Subject-Specific Traits for Excessive Erythrocytosis in Andean Adults Living Permanen-tly at 3,825 Meters Above Sea Level[J].Chest,2014,146:1327- 1336.
• [15] 中华医学会血液学分会.铁过载诊断与治疗的中国专家共识[J].中华血液学杂志，2011,32:572- 574.
• [16] 魏贤.血清叶酸、维生素B12、铁蛋白联合检测对贫血早期的诊断价值[J].临床检验杂志(电子版),2017,6:685- 686.
• [17] 邓燕，秦雪，黄珊，等.广西防城港地区汉族健康成年男性血清叶酸和维生素B12正常参考值的建立[J].中国临床新医学，2011,4:413- 416.Deng Y,Qin X,Huang S,et al.Reference values for serum levels of B12 and folate in Han ehinc males from the Fangchenggang area[J].Zhongguo Linchuang Xinyixue,2011,4:413- 416.
• [18] 高利伟，徐增让，成升魁，等.西藏农村居民食物消费结构及膳食营养特征分析[J].资源科学，2017,39:168- 174.
• [19] 中华人民共和国国家卫生健康委员会.WS/T404.6- 2015.临床常用生化检验项目参考区间第6部分：血清总钙、无机磷、镁、铁[S/OL].(2015- 04- 29).http://www.nhc.gov.cn/wjw/s9492/201504/fc914ad 5981a49a88213940422ad24e1.shtml.
• [20] 中华人民共和国国家卫生健康委员会.WS/T404.9- 2018.临床常用生化检验项目参考区间第9部分：血清C-反应蛋白、前白蛋白、转铁蛋白、β-微球蛋白 [S/OL].(2018- 12- 12).http://www.nhc.gov.cn/wjw/s9492/201812/3728fb3be3fa40ba9cd82b2f4dc597f9.shtml.