1.武汉大学中南医院检验科 湖北 武汉 430071
2.武汉大学泰康医学院(基础医学院)免疫系 湖北 武汉 430071
3.湖北省过敏与免疫重点实验室 湖北 武汉 430071
张沂,女,1999—,医学硕士,主要从事糖尿病的表观遗传学研究,E‑mail: 350489236@qq.com
刘松梅,女,1969—,医学博士,主任技师,教授,博士生导师,主要从事肿瘤与代谢性疾病的表观遗传学研究,E‑mail: smliu@whu.edu.cn
收稿:2024-04-25,
纸质出版:2025-06-25
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张沂,孙月华,章晓联等.葡萄糖对结核分枝杆菌感染和增殖的影响[J].武汉大学学报(医学版),2025,46(06):738-742.
ZHANG Yi,SUN Yuehua,ZHANG Xiaolian,et al.Influence of glucose in Mycobacterium tuberculosis infection and proliferation[J].Medical Journal of Wuhan University,2025,46(06):738-742.
张沂,孙月华,章晓联等.葡萄糖对结核分枝杆菌感染和增殖的影响[J].武汉大学学报(医学版),2025,46(06):738-742. DOI: 10.14188/j.1671-8852.2024.0302.
ZHANG Yi,SUN Yuehua,ZHANG Xiaolian,et al.Influence of glucose in Mycobacterium tuberculosis infection and proliferation[J].Medical Journal of Wuhan University,2025,46(06):738-742. DOI: 10.14188/j.1671-8852.2024.0302.
目的
2
结合临床数据与体外实验,研究葡萄糖对结核分枝杆菌(MTB)感染和增殖的影响。
方法
2
回顾性分析武汉大学中南医院5 957名疑似肺结核病人的MTB核酸检测结果和临床信息。根据MTB核酸检测结果和临床诊断,将研究对象分为糖尿病合并肺结核组(DM
&
TB)、糖尿病组(DM)、肺结核组(TB)和非糖尿病非肺结核组(Control)。利用卡方检验分析糖尿病和非糖尿病人群中MTB感染率的差异性,
t
检验分析肺结核人群中DM
&
TB组和TB组之间MTB的DNA拷贝数差异,以及糖尿病人群中DM
&
TB组和DM组空腹血糖水平的差异性。进一步体外培养减毒牛型结核分枝杆菌(BCG),在7H9培养基中不添加和添加葡萄糖(5.5、33 mmol·L
-1
),连续培养24 d,在不同的时间点测量菌液的
OD
值,分析不同浓度葡萄糖刺激对BCG生长曲线的影响。
结果
2
MTB感染率在糖尿病和非糖尿病人群中存在显著差异(55.98%
vs
6.00%,
χ
2
=704.1,
P
<
0.000 1);糖尿病是MTB感染的风险因素[
OR
=19.917(14.843~26.724),
P
<
0.000 1];DM
&
TB组血糖水平高于DM组(
t
=2.372,
P
=0.019),在年龄匹配的肺结核人群中,DM
&
TB组MTB的DNA拷贝数高于TB组(
t
=2.022,
P
=0.047 7)。体外BCG培养实验结果显示,与正常培养条件(对照组)相比,添加5.5 mmol·L
-1
和33 mmol·L
-1
葡萄糖均可促进BCG增殖。
结论
2
葡萄糖增加了MTB的易感性,糖尿病病人严格控制血糖有助于预防MTB感染和控制MTB增殖。
Objective
2
To study the influence of glucose in
Mycobacterium
tuberculosis (MTB) infection and proliferation using clinical data and
in vitro
experiments.
Methods
2
Firstly
a retrospective analysis was conducted on the nucleic acid of MTB and clinical data of 5 957 patients with suspected pulmonary tuberculosis in Zhongnan Hospital of Wuhan University. Based on the MTB nucleic acid testing results and clinical diagnosis
the subjects were classified into the following groups: diabetes mellitus with pulmonary tuberculosis (DM
&
TB)
diabetes mellitus (DM)
tuberculosis (TB)
as well as non‑diabetic and non‑tuberculosis (Control) groups. The differences in MTB infection rates between diabetic and non‑diabetic groups were analyzed using the chi‑square test. Additionally
t
‑tests were employed to examine the disparities in MTB DNA copy numbers between DM
&
TB and TB individuals within the pulmonary tuberculosis group
as well as the differences in fasting blood glucose levels between the DM
&
TB and DM groups. Subsequently
an
in vitro
experiment was conducted
which involved the cultivation of attenuated
Mycobacterium
bovis Bacillus Calmette‑Guérin (BCG) in 7H9 culture medium supplemented with or without varying concentrations of glucose (5.5 and 33 mmol·L
-1
). The growth curves of the three groups of cultures were measured at different time points over 24 days.
Results
2
There were significantly different MTB infection rates between diabetic and non‑diabetic populations (55.98%
vs
6.00%
χ
2
=704.1
P
<
0.000 1). Diabetes was a risk factor for MTB infection (
OR
=19.917 [14.843‑26.724
]
P
<
0.000 1); The blood glucose levels in the DM
&
TB group were higher than those in the DM group (
t
=2.372
P
=0.019). In age⁃matched pulmonary tuberculosis populations
MTB DNA copy numbers in the DM
&
TB group were higher than those in the TB group
with a significant difference (
t
=2.022
P
=0.0477). Compared with normal culture conditions (control group)
in vitro
BCG culture experiments showed that 5.5 mmol·L
-1
and 33 mmol·L
-1
glucose could promote BCG proliferation.
Conclusion
2
Glucose could increase the susceptibility to MTB infection. Well⁃controlled blood glucose level is beneficial for diabetic patients in preventing MTB infection and lowering MTB proliferation.
HARDING E . WHO global progress report on tuberculosis elimination [J ] . Lancet Respir Med , 2020 , 8 ( 1 ): 19 .
Global tuberculosis report 2023 [R ] . Geneva : World Health Organization ; 2023 .Licence:CC BY‑NC‑SA 3.0 IGO.
DEMIR S , NAWROTH P P , HERZIG S , et al . Emerging targets in type 2 diabetes and diabetic complications [J ] . Adv Sci , 2021 , 8 ( 18 ): e2100275 .
陆菊明 . 《中国2型糖尿病防治指南(2020年版)》读后感 [J ] . 中华糖尿病杂志 , 2021 , 13 ( 4 ): 301 ‑ 304 .
LU J M . Reaction to Guideline for the prevention and treatment of type 2 diabetes mellitus in China ( 2020 edition ) [J ] . Chin J Diabetes Mellit , 2021 , 13 ( 4 ): 301 ‑ 304 .
CAO Y , PARMAR H , SIMMONS A M , et al . Automatic identification of individual rpoB gene mutations responsible for Rifampin resistance in Mycobacterium tuberculosis by use of melting temperature signatures generated by the Xpert MTB/RIF Ultra Assay [J ] . J Clin Microbiol , 2019 , 58 ( 1 ): e00907 ‑ e00919 .
CRESSWELL F V , TUGUME L , BAHR N C , et al . Xpert MTB/RIF Ultra for the diagnosis of HIV‑associated tuberculous meningitis: A prospective validation study [J ] . Lancet Infect Dis , 2020 , 20 ( 3 ): 308 ‑ 317 .
中华医学会 , 中华医学会杂志社 , 中华医学会全科医学分会 , 等 . 肺结核基层诊疗指南(2018年) [J ] . 中华全科医师杂志 , 2019 , 18 ( 008 ): 709 ‑ 717 .
Chinese Medical Association , Chinese Medical Journals Publishing House , Chinese Society of General Practice , et al . Guidelines for primary diagnosis and treatment of pulmonary tuberculosis (2018) [J ] . Chinese Journal of General Practitioners , 2019 , 18 ( 008 ): 709 ‑ 717 .
PAGANI T D , CORRÊA P R , LIMA C , et al . Impact of genomic deletion RD16 on the expression of the Mycobacterium bovis BCG Moreau VapBC47 toxin‑antitoxin system [J ] . Curr Issues Mol Biol , 2023 , 45 ( 8 ): 6538 ‑ 6549 .
NIU C , CHEN Z W , KIM K T , et al . Metformin alleviates hyperglycemia‑induced endothelial impairment by downregulating autophagy via the Hedgehog pathway [J ] . Autophagy , 2019 , 15 ( 5 ): 843 ‑ 870 .
BI Y G , WANG G Y , LIU X D , et al . Low‑after‑high glucose down‑regulated Cx43 in H9c2 cells by autophagy activation via cross‑regulation by the PI3K/Akt/mTOR and MEK/ERK(1/2) signal pathways [J ] . Endocrine , 2017 , 56 ( 2 ): 336 ‑ 345 .
OLIVEIRA HASHIGUCHI L , COX S E , EDWARDS T , et al . How can tuberculosis services better support patients with a diabetes co‑morbidity?A mixed methods study in the Philippines [J ] . BMC Health Serv Res , 2023 , 23 ( 1 ): 1027 .
VAISHYA R , MISRA A , VAISH A , et al . Diabetes and tuberculosis syndemic in India: A narrative review of facts, gaps in care and challenges [J ] . J Diabetes , 2024 , 16 ( 5 ): e13427 .
BARTLETT S , GEMIARTO A T , NGO M D , et al . GPR183 regulates interferons, autophagy, and bacterial growth during Mycobacterium tuberculosis infection and is associated with TB disease severity [J ] . Front Immunol , 2020 , 11 : 601534 .
KEWCHAROENWONG C , SAENWONGSA W , WILLCOCKS S J , et al . Glibenclamide alters interleukin‑8 and interleukin‑1β of primary human monocytes from diabetes patients against Mycobacterium tuberculosis infection [J ] . Tuberculosis , 2020 , 123 : 101939 .
TO K , CAO R Q , YEGIAZARYAN A , et al . Effects of oral liposomal glutathione in altering the immune responses against Mycobacterium tuberculosis and the Mycobacterium bovis BCG strain in individuals with type 2 diabetes [J ] . Front Cell Infect Microbiol , 2021 , 11 : 657775 .
BHAVANAM S , RAYAT G R , KEELAN M , et al . Evaluation of the effect of T regulatory cell depletion and donor BCG vaccination on Mycobacterium tuberculosis H37Ra infection using an in vitro model of human PBMC infection [J ] . Pathog Dis , 2020 , 78 ( 9 ): ftaa068 .
SAITO S , KOBAYASHI I , HOSHINA M , et al . Regulatory role of GgaR (YegW) for glycogen accumulation in Escherichia coli K‑12 [J ] . Microorganisms , 2024 , 12 ( 1 ): 115 .
LUO Z , YUE S , CHEN T , et al . Reduced growth of Staphylococcus aureus under high glucose conditions is associated with decreased pentaglycine expression [J ] . Front Microbiol , 2020 , 11 : 537290 .
VERMA A , KAUR M , LUTHRA P , et al . Immunological aspects of host‑pathogen crosstalk in the co‑pathogenesis of diabetes and latent tuberculosis [J ] . Front Cell Infect Microbiol , 2022 , 12 : 957512 .
PANDA S , SEELAN D M , FAISAL S , et al . Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis [J ] . Eur J Immunol , 2022 , 52 ( 10 ): 1595 ‑ 1609 .
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