北京大学学报(医学版) ›› 2024, Vol. 56 ›› Issue (1): 45-50. doi: 10.19723/j.issn.1671-167X.2024.01.008

• 论著 • 上一篇    下一篇

Ⅲ期牙周炎患者牙周基础治疗前后炎症性贫血相关指标的变化

殳畅,韩烨,孙雨哲,杨再目,侯建霞*()   

  1. 北京大学口腔医学院·口腔医院牙周科,国家口腔医学中心,国家口腔疾病临床医学研究中心,口腔生物材料和数字诊疗装备国家工程研究中心,口腔数字医学北京市重点实验室,北京 100081
  • 收稿日期:2023-10-11 出版日期:2024-02-18 发布日期:2024-02-06
  • 通讯作者: 侯建霞 E-mail:jxhou@163.com
  • 基金资助:
    国家自然科学基金(82071117);北京市自然科学基金(7212136)

Changes of parameters associated with anemia of inflammation in patients with stage Ⅲ periodontitis before and after periodontal initial therapy

Chang SHU,Ye HAN,Yuzhe SUN,Zaimu YANG,Jianxia HOU*()   

  1. Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
  • Received:2023-10-11 Online:2024-02-18 Published:2024-02-06
  • Contact: Jianxia HOU E-mail:jxhou@163.com
  • Supported by:
    the National Natural Science Foundation of China(82071117);the Beijing Natural Science Foundation(7212136)

RICH HTML

  

摘要:

目的: 比较Ⅲ期牙周炎患者与牙周健康者炎症性贫血相关指标的异同,探究牙周基础治疗对Ⅲ期牙周炎患者炎症性贫血指标的影响。方法: 纳入2020年2月至2023年2月于北京大学口腔医院牙周科就诊的Ⅲ期牙周炎患者25名,招募牙周健康者25名,记录人口学信息并进行牙周检查(探诊深度、临床附着丧失、出血指数),采集空腹静脉血。Ⅲ期牙周炎患者经牙周基础治疗后3个月再次行牙周检查并采血。血液分析包括全血细胞分析以及用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测铁调素、铁蛋白、促红细胞生成素(erythro-poietin,EPO)。统计分析由SPSS 21.0统计软件完成,使用独立样本t检验、配对t检验及协方差分析进行组间比较。结果: Ⅲ期牙周炎患者的年龄显著大于牙周健康者[(36.72±7.64)岁vs. (31.44±7.52)岁,P=0.017],血红蛋白显著低于牙周健康者[(134.92±12.71) g/L vs. (146.52±12.51) g/L,P=0.002],铁调素[(48.03±34.44) μg/L vs. (27.42±15.00) μg/L,P=0.009]、铁蛋白[(225.08±103.36) μg/L vs. (155.19±115.38) μg/L,P=0.029]、EPO [(41.28±12.58) IU/L vs. (28.38±10.52) IU/L,P < 0.001]显著高于牙周健康者。用协方差分析校正年龄后,以上趋势维持不变且差异均有统计学意义。经牙周基础治疗后,Ⅲ期牙周炎患者所有牙周指标均有明显改善,血红蛋白[(146.05±15.48) g/L vs. (133.77±13.15) g/L,P < 0.001]显著升高,铁调素[(32.54±18.67) μg/L vs. (48.18±36.74) μg/L,P=0.033]、铁蛋白[(128.52±90.95) μg/L vs. (221.22±102.15) μg/L,P < 0.001]、EPO显著降低[(27.66±19.67) IU/L vs. (39.63±12.48) IU/L,P=0.004]。结论: Ⅲ期牙周炎患者具有炎症性贫血及铁代谢紊乱的倾向,牙周基础治疗可改善这种状况。

关键词: 牙周炎, 炎症性贫血, 铁代谢, 牙周疾病

Abstract:

Objective: To investigate the differences and similarities of parameters associated with anemia of inflammation between patients with stage Ⅲ periodontitis and periodontally healthy volunteers, and to explore the influence of periodontal initial therapy on those indicators. Methods: Patients with stage Ⅲ periodontitis and periodontally healthy volunteers seeking periodontal treatment or prophylaxis at Department of Periodontology, Peking University School and Hospital of Stomatology from February 2020 to February 2023 were enrolled. Their demographic characteristics, periodontal parameters (including probing depth, clinical attachment loss, bleeding index), and fasting blood were gathered before periodontal initial therapy. Three months after periodontal initial therapy, the periodontal parameters of the patients with stage Ⅲ periodontitis were re-evaluated and their fasting blood was collected again. Blood routine examinations (including white blood cells, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume of erythrocytes, and mean corpuscular hemoglobin concentration) were performed. And ferritin, hepcidin, erythropoietin (EPO) were detected with enzyme-linked immunosorbent assay (ELISA). All data analysis was done with SPSS 21.0, independent sample t test, paired t test, and analysis of covariance were used for comparison between the groups. Results: A total of 25 patients with stage Ⅲ periodontitis and 25 periodontally healthy volunteers were included in this study. The patients with stage Ⅲ periodontitis were significantly older than those in periodontally healthy status [(36.72±7.64) years vs. (31.44±7.52) years, P=0.017]. The patients with stage Ⅲ periodontitis showed lower serum hemoglobin [(134.92±12.71) g/L vs. (146.52±12.51) g/L, P=0.002] and higher serum ferritin [(225.08±103.36) μg/L vs. (155.19±115.38) μg/L, P=0.029], EPO [(41.28±12.58) IU/L vs. (28.38±10.52) IU/L, P < 0.001], and hepcidin [(48.03±34.44) μg/L vs. (27.42±15.00) μg/L, P=0.009] compared with periodontally healthy volunteers. After adjusting the age with the covariance analysis, these parameters (hemoglobin, ferritin, EPO, and hepcidin) showed the same trends as independent-sample t test with statistical significance. Three months after periodontal initial therapy, all the periodontal parameters showed statistically significant improvement. The serum hemoglobin raised [(146.05±15.48) g/L vs. (133.77± 13.15) g/L, P < 0.001], while the serum ferritin [(128.52±90.95) μg/L vs. (221.22±102.15) μg/L, P < 0.001], EPO [(27.66±19.67) IU/L vs. (39.63± 12.48) IU/L, P=0.004], and hepcidin [(32.54±18.67) μg/L vs. (48.18±36.74) μg/L, P=0.033] decreased compared with baseline. Conclusion: Tendency of iron metabolism disorder and anemia of inflammation was observed in patients with stage Ⅲ periodontitis, which can be attenuated by periodontal initial therapy.

Key words: Periodontitis, Anemia of inflammation, Iron metabolism, Periodontal diseases

中图分类号: 

  • R781.4

表1

牙周健康组和牙周炎组年龄、性别分布情况"

Items Control Stage Ⅲ periodontitis P
Age/years, ${\bar x}$±s 31.44±7.52 36.72±7.64 0.017
Gender, n
  Male 13 14 0.777
  Female 12 11
PD/mm, ${\bar x}$±s 1.56±0.68 4.71±0.95 < 0.001
BI, ${\bar x}$±s 1.12±0.52 3.44±0.57 < 0.001
CAL/mm, ${\bar x}$±s 0 4.27±0.98 < 0.001

表2

Ⅲ期牙周炎患者与牙周健康者空腹血参数比较"

Items Control, ${\bar x}$±s Stage Ⅲ periodontitis, ${\bar x}$±s P
WBC/(×109/L) 5.90±1.13 6.48±1.74 0.169
RBC/(×1012/L) 4.85±0.45 4.86±0.56 0.962
HGB/(g/L) 146.52±12.51 134.92±12.71 0.002**
HCT 0.43±0.04 0.42±0.04 0.382
MCV/fL 89.24±3.75 87.62±5.81 0.246
MCH/(pg/cell) 29.86±1.56 29.68±2.67 0.763
MCHC/(g/dL) 334.52±10.35 338.2±13.56 0.286
Transferrin/(mg/dL) 268.81±37.86 254.92±47.25 0.254
Ferritin/(μg/L) 155.19±115.38 225.08±103.36 0.029*
Hepcidin/(μg/L) 27.42±15.00 48.03±34.44 0.009**
EPO/(IU/L) 28.38±10.52 41.28±12.58 < 0.001***

表3

Ⅲ期牙周炎患者与牙周健康者空腹血参数的协方差分析"

Items Control, ${\bar x}$±s Stage Ⅲ periodontitis, ${\bar x}$±s P
WBC/(×109/L) 5.79±0.30 6.59±0.30 0.070
RBC/(×1012/L) 4.84±0.11 4.87±0.11 0.811
HGB/(g/L) 146.51±2.63 134.93±2.63 0.004**
HCT 0.43±0.01 0.43±0.01 0.627
MCV/fL 89.08±1.02 87.79±1.02 0.386
MCH/(pg/cell) 29.86±0.46 29.68±0.46 0.784
MCHC/(g/dL) 335.18±2.48 337.54±2.48 0.518
Transferrin/(mg/dL) 269.48±8.92 254.36±8.92 0.250
Ferritin/(μg/L) 152.01±22.75 228.26±22.75 0.026*
Hepcidin/(μg/L) 27.33±5.54 48.13±5.54 0.013*
EPO/(IU/L) 28.64±2.41 41.02±2.41 0.001**

表4

牙周炎患者牙周基础治疗前后临床指标变化"

Items Baseline, ${\bar x}$±s After therapy, ${\bar x}$±s P
PD/mm 4.66±0.88 2.92±0.45 < 0.001
BI 3.46±0.57 1.66±0.74 < 0.001
CAL/mm 4.23±0.89 3.03±0.75 < 0.001

表5

Ⅲ期牙周炎患者牙周基础治疗前后空腹血参数变化"

Items Baseline, ${\bar x}$±s After therapy, ${\bar x}$±s P
WBC/(×109/L) 6.43±1.83 6.28±1.88 0.401
RBC/(×1012/L) 4.85±0.60 4.79±0.56 0.272
HGB/(g/L) 133.77±13.15 146.05±15.48 < 0.001***
HCT 0.42±0.04 0.42±0.04 0.244
MCV/fL 87.40±6.14 87.27±6.19 0.655
MCH/(pg/cell) 29.64±2.83 29.31±2.60 0.051
MCHC/(g/dL) 338.55±14.33 335.18±12.12 0.102
Transferrin/(mg/dL) 257.45±49.62 258.06±34.06 0.957
Ferritin/(μg/L) 221.22±102.15 128.52±90.95 < 0.001***
Hepcidin/(μg/L) 48.18±36.74 32.54±18.67 0.033*
EPO/(IU/L) 39.63±12.48 27.66±19.67 0.004**
1 Lu HX , Tao DY , Lo ECM , et al. The 4th National Oral Health Survey in the mainland of China: Background and methodology[J]. Chin J Dent Res, 2018, 21 (3): 161- 165.
2 Tonetti MS , Greenwell H , Kornman KS . Staging and grading of periodontitis: Framework and proposal of a new classification and case definition[J]. J Periodontol, 2018, 89 (Suppl 1): S159- S172.
3 Jiao J , Jing W , Si Y , et al. The prevalence and severity of periodontal disease in mainland China: Data from the Fourth National Oral Health Survey (2015-2016)[J]. J Clin Periodontol, 2021, 48 (2): 168- 179.
doi: 10.1111/jcpe.13396
4 Guo LN , Yang YZ , Feng YZ . Serum and salivary ferritin and hepcidin levels in patients with chronic periodontitis and type 2 diabetes mellitus[J]. BMC Oral Health, 2018, 18 (1): 63.
doi: 10.1186/s12903-018-0524-4
5 Zheng X , Li X , Zhen J , et al. Periodontitis is associated with stroke[J]. J Transl Med, 2023, 21 (1): 697.
doi: 10.1186/s12967-023-04545-1
6 Gonzalez DA, Bianchi ML, Armada M, et al. Hyposalivation and periodontal disease as oral non-articular characteristics in rheumatoid arthritis [J/OL]. Clin Rheumatol, 2023, doi: 10.1007/s10067-023-06718-1. Online ahead of print. https://link.sprin-ger.com/article/10.1007/s10067-023-06718-1.
7 AlSharief M , Alabdurubalnabi E . Periodontal pathogens and adverse pregnancy outcomes: A narrative review[J]. Life (Basel), 2023, 13 (7): 1559.
8 Shi T , Wang J , Dong J , et al. Periodontopathogens Porphyromonas gingivalis and Fusobacterium nucleatum and their roles in the progression of respiratory diseases[J]. Pathogens, 2023, 12 (9): 1110.
doi: 10.3390/pathogens12091110
9 Zhao C , Kuraji R , Ye C , et al. Nisin a probiotic bacteriocin mitigates brain microbiome dysbiosis and Alzheimer' s disease-like neuroinflammation triggered by periodontal disease[J]. J Neuroinflammation, 2023, 20 (1): 228.
doi: 10.1186/s12974-023-02915-6
10 Beukers N , Su N , van der Heijden G , et al. Periodontitis is associated with multimorbidity in a large dental school population[J]. J Clin Periodontol, 2023, 50 (12): 1621- 1632.
doi: 10.1111/jcpe.13870
11 Ganz T . Anemia of inflammation[J]. N Engl J Med, 2019, 381 (12): 1148- 1157.
doi: 10.1056/NEJMra1804281
12 Thomas C , Thomas L . Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency[J]. Clin Chem, 2002, 48 (7): 1066- 1076.
doi: 10.1093/clinchem/48.7.1066
13 Handelman GJ , Levin NW . Iron and anemia in human biology: A review of mechanisms[J]. Heart Fail Rev, 2008, 13 (4): 393- 404.
doi: 10.1007/s10741-008-9086-x
14 张梦雪, 王小钦. 铁稳态失调相关的炎症性贫血发病机制及诊断进展[J]. 诊断学理论与实践, 2018, 17 (5): 601- 605.
15 de Las Cuevas Allende R , Díaz de Entresotos L , Conde Díez S . Anaemia of chronic diseases: Pathophysiology, diagnosis and treatment[J]. Med Clin (Barc), 2021, 156 (5): 235- 242.
doi: 10.1016/j.medcli.2020.07.035
16 Hutter JW , van der Velden U , Varoufaki A , et al. Lower numbers of erythrocytes and lower levels of hemoglobin in periodontitis patients compared to control subjects[J]. J Clin Periodontol, 2001, 28 (10): 930- 936.
doi: 10.1034/j.1600-051x.2001.028010930.x
17 郜洪宇, 徐菁玲, 孟焕新, 等. 牙周基础治疗对2型糖尿病伴慢性牙周炎患者红细胞、血小板相关指标的影响[J]. 北京大学学报(医学版), 2020, 52 (4): 750- 754.
18 Nibali L , Darbar U , Rakmanee T , et al. Anemia of inflammation associated with periodontitis: Analysis of two clinical studies[J]. J Periodontol, 2019, 90 (11): 1252- 1259.
doi: 10.1002/JPER.19-0124
19 Kolte RA , Kolte AP , Deshpande NM . Assessment and comparison of anemia of chronic disease in healthy subjects and chronic periodontitis patients: A clinical and hematological study[J]. J Indian Soc Periodontol, 2014, 18 (2): 183- 186.
doi: 10.4103/0972-124X.131321
20 Pradeep AR , Anuj S . Anemia of chronic disease and chronic periodontitis: Does periodontal therapy have an effect on anemic status?[J]. J Periodontol, 2011, 82 (3): 388- 394.
doi: 10.1902/jop.2010.100336
21 Han Y , Huang W , Meng H , et al. Pro-inflammatory cytokine interleukin-6-induced hepcidin, a key mediator of periodontitis-related anemia of inflammation[J]. J Periodontal Res, 2021, 56 (4): 690- 701.
doi: 10.1111/jre.12865
22 Han Y , Luo Z , Yue ZG , et al. The tendency of anemia of inflammation in periodontal diseases[J]. Clin Sci (Lond), 2023, 137 (3): 251- 264.
doi: 10.1042/CS20220524
23 Patel MD , Shakir QJ , Shetty A . Interrelationship between chronic periodontitis and anemia: A 6-month follow-up study[J]. J Indian Soc Periodontol, 2014, 18 (1): 19- 25.
doi: 10.4103/0972-124X.128194
24 Massey AC . Microcytic anemia. Differential diagnosis and management of iron deficiency anemia[J]. Med Clin North Am, 1992, 76 (3): 549- 566.
doi: 10.1016/S0025-7125(16)30339-X
25 Weiss G , Ganz T , Goodnough LT . Anemia of inflammation[J]. Blood, 2019, 133 (1): 40- 50.
doi: 10.1182/blood-2018-06-856500
26 Chakraborty S , Tewari S , Sharma RK , et al. Effect of non-surgical periodontal therapy on serum ferritin levels: An interventional study[J]. J Periodontol, 2014, 85 (5): 688- 696.
doi: 10.1902/jop.2013.130107
27 Ong DS , Wang L , Zhu Y , et al. The response of ferritin to LPS and acute phase of Pseudomonas infection[J]. J Endotoxin Res, 2005, 11 (5): 267- 280.
doi: 10.1177/09680519050110050301
28 Huang W , Zhan Y , Zheng Y , et al. Up-regulated ferritin in periodontitis promotes inflammatory cytokine expression in human periodontal ligament cells through transferrin receptor via ERK/P38 MAPK pathways[J]. Clin Sci (Lond), 2019, 133 (1): 135- 148.
doi: 10.1042/CS20180679
29 Johnston PA , Grandis JR . STAT3 signaling: Anticancer strategies and challenges[J]. Mol Interv, 2011, 11 (1): 18- 26.
doi: 10.1124/mi.11.1.4
30 Drakesmith H , Prentice AM . Hepcidin and the iron-infection axis[J]. Science, 2012, 338 (6108): 768- 772.
doi: 10.1126/science.1224577
31 Malyszko J , Malyszko JS , Matuszkiewicz-Rowinska J . Hepcidin as a therapeutic target for anemia and inflammation associated with chronic kidney disease[J]. Expert Opin Ther Targets, 2019, 23 (5): 407- 421.
doi: 10.1080/14728222.2019.1599358
32 Arndt S , Maegdefrau U , Dorn C , et al. Iron-induced expression of bone morphogenic protein 6 in intestinal cells is the main regulator of hepatic hepcidin expression in vivo[J]. Gastroenterology, 2010, 138 (1): 372- 382.
33 Kautz L , Jung G , Du X , et al. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of beta-thalassemia[J]. Blood, 2015, 126 (17): 2031- 2037.
[1] 胡玉如,刘娟,李文静,赵亦兵,李启强,路瑞芳,孟焕新. Ⅲ期或Ⅳ期牙周炎患者龈沟液中有机酸浓度与牙周炎的关系[J]. 北京大学学报(医学版), 2024, 56(2): 332-337.
[2] 张晗,秦亦瑄,韦帝远,韩劼. 牙周炎患者种植修复维护治疗依从性的影响因素[J]. 北京大学学报(医学版), 2024, 56(1): 39-44.
[3] 裴喜燕,阳雯,欧阳翔英,孙凤. 牙周内窥镜下根面清创与牙周翻瓣术疗效比较[J]. 北京大学学报(医学版), 2023, 55(4): 716-720.
[4] 温静,欧阳翔英,裴喜燕,邱善湧,刘健如,刘文逸,曹采方. 重度牙周炎患者4年自然进展失牙的多因素分析[J]. 北京大学学报(医学版), 2023, 55(1): 70-77.
[5] 朱小玲,李文静,王宪娥,宋文莉,徐莉,张立,冯向辉,路瑞芳,释栋,孟焕新. 细胞色素B-245α链及胆固醇酯转运蛋白基因多态性与广泛型侵袭性牙周炎易感性的关系[J]. 北京大学学报(医学版), 2022, 54(1): 18-22.
[6] 徐欣然,霍芃呈,和璐,孟焕新,朱筠轩,靳东思奇. 伴与不伴糖尿病的牙周炎患者牙周基础治疗的疗效比较及其与白细胞水平的相关分析[J]. 北京大学学报(医学版), 2022, 54(1): 48-53.
[7] 郜洪宇,孟焕新,侯建霞,黄宝鑫,李玮. 钙结合蛋白在健康牙周组织和实验性牙周炎组织的表达分布[J]. 北京大学学报(医学版), 2021, 53(4): 744-749.
[8] 刘建,王宪娥,吕达,乔敏,张立,孟焕新,徐莉,毛铭馨. 广泛型侵袭性牙周炎患者牙根形态异常与相关致病基因的关联[J]. 北京大学学报(医学版), 2021, 53(1): 16-23.
[9] 郜洪宇,徐菁玲,孟焕新,和璐,侯建霞. 牙周基础治疗对2型糖尿病伴慢性牙周炎患者红细胞、血小板相关指标的影响[J]. 北京大学学报(医学版), 2020, 52(4): 750-754.
[10] 闫乐,王宪娥,詹雅琳,苗莉莉,韩烨,张楚人,岳兆国,胡文杰,侯建霞. 超声龈下清创联合手工根面平整术治疗重度牙周炎的临床效果[J]. 北京大学学报(医学版), 2020, 52(1): 64-70.
[11] 张勇,刘畅,陈彬,陈帆,段晋瑜,张孟钧,焦剑. 糖尿病前期患者糖代谢异常与慢性牙周炎的相关性[J]. 北京大学学报(医学版), 2020, 52(1): 71-76.
[12] 朱洁,李建红,袁婷婷,和璐,梁宇红. 绝经期妇女牙周状况与骨质密度的相关性分析[J]. 北京大学学报(医学版), 2019, 51(6): 1115-1118.
[13] 杨一帆,栾庆先. 北京某社区35岁以上居民吸烟与牙周健康状况关系的调查[J]. 北京大学学报(医学版), 2019, 51(6): 1144-1149.
[14] 石姝雯,孟洋,焦剑,李文静,孟焕新,栾庆先,王万春. 根分叉病变患牙经牙周非手术治疗后5年失牙状况及多因素分析[J]. 北京大学学报(医学版), 2019, 51(5): 913-918.
[15] 杜仁杰,焦剑,周彦恒,施捷. 侵袭性牙周炎患者正畸前后的咬合变化[J]. 北京大学学报(医学版), 2019, 51(5): 919-924.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 杨天智, 陈大兵, 张强. 不同吸收促进剂及酶抑制剂对胰岛素体内及体外口腔黏膜渗透性的影响[J]. 北京大学学报(医学版), 2001, 33(3): 238 -242 .
[2] 柳晓辉, 那加, 刘玲玲, 罗斌. 头颈部血管肉瘤3例[J]. 北京大学学报(医学版), 2001, 33(3): 288 -289 .
[3] 梁成, 王兴, 伊彪, 李自力, 王晓霞. 骨性颞下颌关节强直伴小颌畸形及阻塞性睡眠呼吸暂停综合征的牵引成骨治疗[J]. 北京大学学报(医学版), 2002, 34(2): 112 -116 .
[4] 郭应禄, 张凯. 临床研究所要创高水平医疗[J]. 北京大学学报(医学版), 2002, 34(5): 431 -433 .
[5] 胡维亨, 任军. 人乙型肝炎病毒DNA阳性血清对人骨髓间充质干细胞向肝细胞分化的影响[J]. 北京大学学报(医学版), 2008, 40(5): 459 -464 .
[6] 龚继芳, 袁艳华, 宋国红, 余靖, 贾军, 任军. CD44+/CD24-/low/ABCG2-乳腺癌干细胞比例增高与临床治疗相关的探索性研究[J]. 北京大学学报(医学版), 2008, 40(5): 465 -470 .
[7] 邸立军, 任军, 宋国红, 余靖, 方健, 车利, 祝毓琳. 自体外周血CD34+干细胞来源树突状细胞体外扩增治疗恶性体腔积液[J]. 北京大学学报(医学版), 2008, 40(5): 486 -488 .
[8] 张勇, 栾庆先. 牙周维护治疗在保持牙周长期疗效中的作用[J]. 北京大学学报(医学版), 2011, 43(1): 29 -33 .
[9] 曾百进, 余日月, 周永胜, 徐军, 倪永伟, 刘云松, 许永伟. rhTNF-α对成骨向分化前后的人脂肪基质细胞分泌血管生成相关生长因子的影响[J]. 北京大学学报(医学版), 2009, 41(5): 565 -570 .
[10] 张旗, 何湘君, 刘玉京, 马丽萍, 潘秀英 . 实时定量PCR阵列检测小鼠大脑组织microRNA表达谱[J]. 北京大学学报(医学版), 2009, 41(2): 152 -157 .