目的:探讨年龄相关性疾病对免疫功能以及炎症因子水平影响的临床意义。方法:回顾性分析年龄相关性疾病患者192例以及对照组80例,根据不同疾病分为高血压组、糖尿病组、高血压合并糖尿病组、高血压或糖尿病合并急性脑梗死组,根据年龄各组进行亚组分析,分为年老组、年轻组,统计分析各组间淋巴细胞亚群和炎症因子的变化情况。结果:1) CD3-CD56+(NK)%、CD8+(Ts)%、CD4+/CD8+(Th/Ts)、IL-6在高血压或糖尿病合并脑梗死组显著升高;CD3-CD56+(NK)%、IL-6在高血压合并糖尿病组中显著升高,但CD4+/CD8+(Th/Ts)显著降低。2) 除糖尿病组外,各组中年老组较年轻组CD4+/CD8+(Th/Ts)降低;除高血压组外,各组年老组较年轻组CD19+(B)%降低;所有分组中老年组较年轻组CD3-CD56(NK)%、IL-6均升高。结论:合并年龄相关性疾病数量越多免疫功能降低越显著;当慢性年龄相关性疾病出现急性病变如急性脑梗死时,免疫系统功能激活、促炎反应增强;年龄在年龄相关性疾病的免疫功能下降和炎症水平的升高中具有促进作用。 Objective: To explore the clinical significance of the effect of age-related diseases on immune func-tion and inflammatory factors. Methods: 192 patients with age-related diseases and 80 patients in the control group were divided into hypertension group, diabetes mellitus group, hypertension complicated with diabetes group, hypertension or diabetes mellitus complicated with acute cere-bral infarction group according to different diseases. The patients were divided into old group and young group, and the changes of lymphocyte subsets and inflammatory factors were statistically analyzed. Results: 1) CD3-CD56+(NK)%, CD8+(Ts)%, CD4+/CD8+(Th/Ts), IL-6 increased significant-ly in patients with hypertension or diabetes mellitus complicated with cerebral infarction; CD3-CD56+(NK)%, IL-6 was significantly increased in hypertension complicated with diabetes, but CD4+/CD8+(Th/Ts) was significantly decreased. 2) Except for diabetes group, CD4+/CD8+(Th/Ts) in middle-aged group was lower than that in young group, CD19+(B)% in old group was lower than that in young group except hypertension group, and CD3-CD56 (NK)% and IL-6 in all groups were higher than those in young group. Conclusion: The more the number of age-related diseases, the more significant the decrease of immune function; When chronic age-related diseases appear acute lesions such as acute cerebral infarction, the immune system function is activated and the pro-inflammatory response is enhanced; Age plays a promoting role in the decline of immune func-tion of age-related diseases and the promotion of inflammatory level.
目的:探讨年龄相关性疾病对免疫功能以及炎症因子水平影响的临床意义。方法:回顾性分析年龄相关性疾病患者192例以及对照组80例,根据不同疾病分为高血压组、糖尿病组、高血压合并糖尿病组、高血压或糖尿病合并急性脑梗死组,根据年龄各组进行亚组分析,分为年老组、年轻组,统计分析各组间淋巴细胞亚群和炎症因子的变化情况。结果:1) CD3-CD56+(NK)%、CD8+(Ts)%、CD4+/CD8+(Th/Ts)、IL-6在高血压或糖尿病合并脑梗死组显著升高;CD3-CD56+(NK)%、IL-6在高血压合并糖尿病组中显著升高,但CD4+/CD8+(Th/Ts)显著降低。2) 除糖尿病组外,各组中年老组较年轻组CD4+/CD8+(Th/Ts)降低;除高血压组外,各组年老组较年轻组CD19+(B)%降低;所有分组中老年组较年轻组CD3-CD56(NK)%、IL-6均升高。结论:合并年龄相关性疾病数量越多免疫功能降低越显著;当慢性年龄相关性疾病出现急性病变如急性脑梗死时,免疫系统功能激活、促炎反应增强;年龄在年龄相关性疾病的免疫功能下降和炎症水平的升高中具有促进作用。
年龄相关性疾病,免疫功能,炎症因子
Meixiang Zhong1, Yajuan Wang2, Lulu Xu1, Yuyuan Yang1, Meng Wang1, Moxin Luan1, Xueping Zheng1*
1Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Qingdao Shandong
2Department of Geriatric Medicine, The 8th People’s Hospital of Qingdao, Qingdao Shandong
Received: Apr. 16th, 2022; accepted: May 10th, 2022; published: May 17th, 2022
Objective: To explore the clinical significance of the effect of age-related diseases on immune function and inflammatory factors. Methods: 192 patients with age-related diseases and 80 patients in the control group were divided into hypertension group, diabetes mellitus group, hypertension complicated with diabetes group, hypertension or diabetes mellitus complicated with acute cerebral infarction group according to different diseases. The patients were divided into old group and young group, and the changes of lymphocyte subsets and inflammatory factors were statistically analyzed. Results: 1) CD3-CD56+(NK)%, CD8+(Ts)%, CD4+/CD8+(Th/Ts), IL-6 increased significantly in patients with hypertension or diabetes mellitus complicated with cerebral infarction; CD3-CD56+(NK)%, IL-6 was significantly increased in hypertension complicated with diabetes, but CD4+/CD8+(Th/Ts) was significantly decreased. 2) Except for diabetes group, CD4+/CD8+(Th/Ts) in middle-aged group was lower than that in young group, CD19+(B)% in old group was lower than that in young group except hypertension group, and CD3-CD56 (NK)% and IL-6 in all groups were higher than those in young group. Conclusion: The more the number of age-related diseases, the more significant the decrease of immune function; When chronic age-related diseases appear acute lesions such as acute cerebral infarction, the immune system function is activated and the pro-inflammatory response is enhanced; Age plays a promoting role in the decline of immune function of age-related diseases and the promotion of inflammatory level.
Keywords:Age-Related Diseases, Immunity, Inflammatory Factor
Copyright © 2022 by author(s) and Hans Publishers Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).
http://creativecommons.org/licenses/by/4.0/
随着年龄的增加,人体会因为机体功能的减退、代谢的失调、储备的降低等因素的叠加而逐渐走向一个衰老的过程,在此过程中会罹患各种慢性疾病,包括高血压、糖尿病、脑梗死等,这些疾病的发生均与年龄增长有关,因此被统称为年龄相关疾病(age-related diseases, ARDs) [
既往研究表明,大多数与年龄相关的慢性病本质上是炎症性的,长期、低水平的慢性炎症以及促炎因子和抗炎因子的平衡失调,增加了内皮损伤、血管重塑损伤、动脉粥样硬化和胰岛素抵抗的可能性,从而增加了ARDs的风险 [
选取2020年1月至2021年7月青岛大学附属医院老年医学科收治的患者,排除急性感染、肿瘤、免疫系统疾病、器官功能衰竭的患者,共纳入病例192例,根据疾病分为4组:高血压组65例、糖尿病组46例、高血压合并糖尿病组36例、高血压或糖尿病合并急性脑梗死组45例,其中急性脑梗死组均为发病7天内入院,从查体中心选取健康对照者共80例。根据WHO老年人群分类标准,每个疾病组和对照组分别以年龄65岁分组,大于或等于65岁为年老组,小于65岁为年轻组。本研究为回顾性研究,已获得青岛大学附属医院伦理委员会批准(伦理号:QYFM WZLL 26928),本研究遵守《赫尔辛基宣言》,委员会已免除书面知情同意。
本研究所有数据分析均通过SPSS 25.0完成,计量资料符合正态分布用x ± s表示,两组间比较采用T检验,多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验;定性资料以率表示,两组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis检验。P < 0.05为差异有统计学意义。
对照组与病例组以及病例组各组间在年龄、性别、吸烟、饮酒、甘油三酯、总胆固醇、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)比较,差异均无统计学意义(P > 0.05)。(表1)
组别 | 对照组 | 高血压组 | 糖尿病组 | 高血压合并糖尿病组 | 高血压或糖尿病合并急性脑梗死组 | F/H | P |
---|---|---|---|---|---|---|---|
人数 | 80 | 65 | 46 | 36 | 45 | ||
性别[男/女,例(%)] | 37 (46.3)/ 43 (53.8) | 34 (53.1)/ 30 (46.9) | 28 (60.9) /18 (39.1) | 25 (69.4)/ 11 (30.6) | 28 (62.2) /17 (37.8) | 6.97 | 0.137 |
年龄(岁) | 60.7 ± 9.82 | 63.09 ± 11.73 | 62.35 ± 11.1 | 63.72 ± 13.3 | 65.38 ± 11.9 | 1.30 | 0.270 |
吸烟[例(%)] | 10 (12.5) | 10 (15.6) | 8 (17.4) | 4 (11.1) | 6 (13.3) | 3.81 | 0.432 |
饮酒[例(%)] | 8 (10) | 11 (17.2) | 6 (13.0) | 4 (11.1) | 5 (11.1) | 1.76 | 0.770 |
甘油三酯(mmol/l) | 1.64 ± 0.69 | 1.65 ± 0.86 | 1.83 ± 0.87 | 1.91 ± 1.1 | 1.93 ± 0.62 | 1.67 | 0.156 |
总胆固醇(mmol/l) | 4.56 ± 1.09 | 4.63 ± 0.77 | 4.48 ± 1.2 | 4.54 ± 1.33 | 4.7 ± 1.17 | 0.26 | 0.898 |
HDL-C (mmol/l) | 1.43 ± 0.31 | 1.37 ± 0.21 | 1.40 ± 0.26 | 1.36 ± 0.34 | 1.42 ± 0.30 | 0.56 | 0.685 |
LDL-C (mmol/l) | 2.47 ± 0.72 | 2.56 ± 0.64 | 2.57 ± 0.76 | 2.45 ± 0.93 | 2.51 ± 0.77 | 0.24 | 0.916 |
表1. 病例组和对照组一般资料对比结果
CD4+CD25+(Treg)%、CD4+(Th)%、CD19+(B)%在各组间无差异(P > 0.05);CD8+(Ts)%在高血压合并糖尿病组和高血压或糖尿病合并急性脑梗死组升高(P < 0.05);CD4+/CD8+(Th/Ts)、CD3-CD56(NK)%在高血压或糖尿病合并脑梗死组显著升高(P < 0.05),但CD4+/CD8+(Th/Ts)在高血压合并糖尿病组降低(P < 0.05)。(表2)
组别 | 对照组 | 高血压组 | 糖尿病组 | 高血压合并糖尿病组 | 高血压或糖尿病合并急性脑梗死组 |
---|---|---|---|---|---|
CD4+CD25+T | 2.89 ± 1.11 | 3.19 ± 1.35 | 3.20 ± 1.45 | 3.00 ± 1.18 | 3.08 ± 1.18 |
CD4+T | 45.52 ± 8.20 | 45.88 ± 6.43 | 44.98 ± 6.65 | 44.74 ± 8.75 | 45.54 ± 8.28 |
CD8+T | 23.13 ± 7.42*# | 22.68 ± 6.14*# | 22.03 ± 6.80*# | 26.40 ± 9.82* | 28.03 ± 7.42# |
CD4+T/CD8+T | 2.08 ± 0.64*# | 1.85 ± 0.58*# | 1.91 ± 0.69*# | 1.70 ± 0.48* | 2.48 ± 0.99# |
CD19B | 14.0 ± 5.27 | 14.25 ± 4.91 | 15.1 ± 5.41 | 14.49 ± 5.92 | 14.5 ± 5.55 |
CD3-CD56+NK | 9.67 ± 5.56*# | 9.93 ± 4.72*# | 8.98 ± 5.71*# | 12.5 ± 7.75 | 12.40 ± 7.89 |
表2. 各组间淋巴细胞亚群比较
注:单位(%);#与“高血压合并糖尿病组”比较P < 0.05;*与“高血压或糖尿病合并急性脑梗死组”比较P < 0.05。
IL-6在病例组中较对照组显著升高(P < 0.05);其余炎症因子在各组间无明显差异(P > 0.05)。(表3)
组别 | 对照组 | 高血压组 | 糖尿病组 | 高血压合并糖尿病组 | 高血压或糖尿病合并急性脑梗死组 |
---|---|---|---|---|---|
IL-5 | 1.39 ± 0.69 | 1.34 ± 0.92 | 1.20 ± 0.49 | 1.35 ± 0.70 | 1.41 ± 0.83 |
IFN-α | 1.78 ± 0.64 | 1.78 ± 0.84 | 1.60 ± 0.44 | 1.64 ± 0.65 | 1.63 ± 0.90 |
IL-2 | 1.44 ± 0.97 | 1.55 ± 0.97 | 1.62 ± 0.63 | 1.41 ± 0.46 | 1.53 ± 0.86 |
IL-6 | 3.91 ± 2.20* | 5.52 ± 2.73*# | 5.67 ± 3.00*# | 6.11 ± 3.28*# | 8.68 ± 4.33# |
IL-1β | 2.99 ± 1.10 | 2.96 ± 1.04 | 2.98 ± 0.89 | 3.05 ± 1.26 | 3.01 ± 0.90 |
IL-10 | 1.06 ± 0.61 | 1.14 ± 0.82 | 1.17 ± 0.39 | 0.95 ± 0.47 | 0.96 ± 0.30 |
IFN-γ | 3.47 ± 2.18 | 3.54 ± 1.84 | 3.63 ± 1.98 | 3.46 ± 1.97 | 3.48 ± 1.88 |
IL-8 | 3.12 ± 1.38 | 3.01 ± 1.34 | 3.47 ± 1.18 | 3.15 ± 1.41 | 3.51 ± 1.17 |
IL-17 | 1.58 ± 0.68 | 1.50 ± 0.78 | 1.35 ± 0.75 | 1.58 ± 0.61 | 1.49 ± 0.72 |
IL-4 | 1.24 ± 0.87 | 1.35 ± 0.41 | 1.37 ± 0.46 | 1.17 ± 0.41 | 1.19 ± 0.43 |
IL-12P | 1.45 ± 0.84 | 1.36 ± 0.48 | 1.29 ± 0.35 | 1.36 ± 0.54 | 1.25 ± 0.46 |
TNF-α | 1.73 ± 1.05 | 1.84 ± 0.87 | 1.76 ± 0.72 | 1.59 ± 0.71 | 1.68 ± 0.97 |
表3. 各组间炎症因子比较分析
注:单位(pg/mL);#与“对照组”比较P < 0.05;*与“高血压或糖尿病合并急性脑梗死组”比较P < 0.05。
IL-6在病例组中较对照组显著升高(P < 0.05),其中高血压或糖尿病合并脑梗死组升高最明显(P < 0.05)。(图1)
图1. 各病例组血清IL-6水平的变化
除糖尿病组外,各组中年老组较年轻组CD4+/CD8+(Th/Ts)降低;除高血压组外,各组中年老组较年轻组CD19+(B)%降低;所有分组中年老组较年轻组CD3-CD56(NK)%、IL-6均升高。(图2~5)
图2. 不同年龄血清IL-6水平的变化
图3. 不同年龄CD4+T/CD8+T的变化
图4. 不同年龄CD19+(B)%的变化
图5. 不同年龄CD3-CD56(NK)%的变化
淋巴细胞比例的失衡是免疫系统的功能下降的重要原因。T细胞起源于胸腺,根据与其相结合的受体可分CD4+T细胞和CD8+T细胞,CD4+T具有辅助T细胞活化、介导B细胞抗体生成和活化巨噬细胞等功能,而CD8+为抑制杀伤细胞,具有抑制T细胞活化,抑制抗体产生和产生细胞毒等作用。CD4+T/CD8+T比值是衡量免疫功能的重要指标,在健康成年人中CD4+T/CD8+T比值约为2:1,比值降低则表明机体处于免疫抑制状态,免疫功能降低 [
在高血压或糖尿病合并急性脑梗死组中虽然CD8+(Ts)%显著升高,但CD4+T/CD8+T比值并未呈现下降变化反而升高。这可能与急性脑梗死激发的应激反应有关,既往研究证实脑组织急性缺血缺氧将会触发中枢神经系统和免疫系统,激活炎症反应和免疫应答 [
随着年龄的增长,长期暴露在抗原环境下导致老年人较年轻人外周血中初始T、B细胞的数量和比率显著减少,而记忆性T、B细胞的数量增多,并且随着衰老进程的发展,胸腺和骨髓的萎缩使得向外输出的初始T、B细胞数量逐渐减少,外周血中T、B细胞的种类和数量也随之下降 [
慢性无菌性炎症与ARDs密切相关 [
总之,在年龄和ARDs的影响下,人体免疫功能逐渐降低和慢性炎症水平持续存在并呈上升趋势。因此,我们可以通过外周血免疫细胞的变化来预测ARDs患者的免疫功能状态,从而来预估疾病的预后,也可以通过抑制炎症因子水平来延缓ARDs的进展。但是,ARDs的进展过程是漫长的,ARDs的影响因素也不仅仅是免疫系统和炎症因子的影响。因此,对于ARDs研究还需从其他方面继续进行补充和研究,为减缓衰老、治疗疾病提供新途径。
钟美香,王亚娟,徐璐璐,杨玉媛,王 萌,栾墨馨,郑雪平. 年龄相关性疾病中免疫功能及炎症因子的变化研究Study on the Changes of Adaptive Immune Function and Inflammatory Factors in Age-Related Diseases[J]. 临床医学进展, 2022, 12(05): 4054-4062. https://doi.org/10.12677/ACM.2022.125587