新诊断的 2 型糖尿病患者血液中自然杀伤细胞的含量和超微结构

V.V. Popova, K.P. Zak, M. Tronko
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引用次数: 0

摘要

背景。在新诊断的 2 型糖尿病(T2DM)患者中,发现外周血(PB)中自然杀伤(NK)细胞(CD56+)的绝对数量有少量下降,但在统计学上有显著意义,尤其是伴有肥胖的患者。有鉴于此,本报告的主要目的之一是进一步研究 NK 细胞在新诊断的 T2DM 患者(包括肥胖患者)中的作用。为此,本研究采用流式细胞术与扫描和透射电子显微镜相结合的方法来确定 T2DM 患者血浆中 CD56+ 细胞的数量和功能。材料和方法我们对 144 名年龄在 40-70 岁、新诊断为 T2DM 的男女患者进行了检查,这些患者没有其他急性或慢性疾病,之前也未服用过任何降糖药物。对照组由 50 名 40-65 岁、血糖正常且未患 COVID-19 疾病的健康人组成。研究结果我们的研究发现,与健康对照组相比,未经治疗的新诊断 T2DM 患者血浆中 CD56+ 细胞的绝对数量有非常小的统计学意义的下降。结合流式细胞术(FACS 法)、透射电子显微镜和扫描电子显微镜观察 T2DM 患者,发现 CD56+ 细胞的超微结构发生了显著变化,表明其功能下降(细胞膜表面更光滑的细胞数量增加、细胞质中被认为是细胞因子和穿孔素主要生产者的嗜氮颗粒数量急剧减少、平行管状结构出现、细胞功能下降的生物标志物、高尔基体结构破坏、颗粒状内质网等)。).获得的数据表明,在人类 T2DM 发展的初期阶段,NK 细胞的功能明显减弱,因此机体的天然免疫防御功能也随之减弱,这也解释了为什么糖尿病患者对各种病毒和感染(包括 COVID-19)的易感性增加,临床病程更严重,死亡率增加。结论研究表明,处于 T2DM 初期阶段的 T2DM 患者,其天然免疫最重要的细胞元素--CD56+ 细胞的亚显微组织急剧紊乱,这表明天然免疫防御功能减弱。这是糖尿病患者对包括 SARS-CoV-2 在内的各种病原体感染的敏感性增加、临床病程更严重和死亡率增加的主要原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Content and ultrastructure of natural killer cells in the blood of patients with newly diagnosed type 2 diabetes mellitus
Background. In patients with newly diagnosed type 2 diabetes mellitus (T2DM), a small but statistically significant decrease in absolute number of natural killer (NK) cells (CD56+) in the peripheral blood (PB) was found, especially pronounced with concomitant obesity. In connection with the above, one of the main aims of the present report was to further study the role of NK cells in patients with newly diagnosed T2DM, including those with obesity. For this purpose, a combination of flow cytometry methods with scanning and transmission electron microscopy was used to determine the number and function of CD56+ cells in the PB of patients with T2DM. Materials and methods. We examined 144 patients of both sexes with newly diagnosed T2DM aged 40–70 years who had no other acute or chronic diseases and had not previously taken any hypoglycemic drugs. The control group consisted of 50 healthy individuals with normoglycemia aged 40–65 years who had not COVID-19 disease. Results. Our studies have found that in untreated patients with newly diagnosed T2DM compared to healthy controls, there is a very small statistically significant decrease in the absolute number of CD56+ cells in the PB. When combining flow cytometry (FACS method), transmission and scanning electron microscopy in patients with T2DM, a significant change in the ultrastructure of CD56+ cells was revealed, indicating a decrease in their function (an increase in the number of cells with a smoother surface of the cell membrane, a sharp decrease in the number of azurophilic granules in the cytoplasm considered the main producer of cytokines and perforins, the appearance of parallel tubular structures, biomarkers of decreased cell function, a disruption of the Golgi apparatus structure, granular endoplasmic reticulum, etc.). The data obtained indicate that at the initial stage of T2DM development in humans, there is a pronounced weakening in the function of NK cells and, consequently, the natural immune defense of the body and explain the increased susceptibility of diabetics to various viruses and infections, including COVID-19, and also more severe clinical course and increased mortality. Conclusions. The conducted studies show that in patients with T2DM who are at the initial stage of T2DM, there is a sharp disturbance in the submicroscopic organization of CD56+ cells, the most important cellular element of natural immunity, which suggests a weakening of the function of natural immune defense. It is the main cause of increased sensitivity of diabetic patients to infection with various pathogens, including the SARS-CoV-2, as well as more severe clinical course and increased mortality rate.
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