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2 型糖尿病患者炎症标志物与昼夜节律时钟基因表达受损的相关性。

Correlation between inflammatory markers and impaired circadian clock gene expression in type 2 diabetes mellitus.

机构信息

Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China.

NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China.

出版信息

Diabetes Res Clin Pract. 2019 Oct;156:107831. doi: 10.1016/j.diabres.2019.107831. Epub 2019 Aug 30.

Abstract

AIM

Circadian rhythm controls a wide variety of physiological processes in the body. Disruption of the circadian clock in metabolic tissues may increase the risk of diabetes, obesity, and metabolic syndrome. The following study investigated whether the expression of clock genes of peripheral blood cells is impaired in type 2 diabetes (DT2) and whether inflammatory markers are associated with circadian clock gene expression in DT2 patients.

MATERIALS AND METHODS

Blood samples were obtained from 36 DT2 patients and 14 non-diabetic volunteers. Transcript levels of circadian clock genes were analyzed using real-time quantitative PCR; plasma inflammatory markers were measured by ELISA or clinical laboratory test.

RESULTS

The CLOCK, BMAL1, PER1, CRY1 and CRY2 mRNA levels were decreased in the diabetic patients. In addition, HbA1c levels were negatively correlated with BMAL1, PER1 and CRY1 mRNA levels. The levels of IL-6, TNF-α and CRP were higher in diabetic subjects compared to control subjects. Impaired expression of circadian clock gene was interrelated with the elevated levels of plasma IL-6 and TNF. Moreover, a multiple linear regression showed that plasma IL-6 level was correlated with impaired expression of circadian clock gene.

CONCLUSIONS

Circadian clock genes are reduced in peripheral leucocytes of DT2 patients. Furthermore, impaired expression of circadian clock gene are interrelated with the elevated levels of plasma inflammatory markers.

摘要

目的

昼夜节律控制着人体的多种生理过程。代谢组织中生物钟的紊乱可能会增加患糖尿病、肥胖症和代谢综合征的风险。本研究旨在探讨 2 型糖尿病(DT2)患者外周血细胞的时钟基因表达是否受损,以及炎症标志物是否与 DT2 患者的生物钟基因表达相关。

材料和方法

采集 36 例 DT2 患者和 14 例非糖尿病志愿者的血样。采用实时定量 PCR 分析昼夜节律钟基因的转录水平;通过 ELISA 或临床实验室检测测量血浆炎症标志物。

结果

糖尿病患者的 CLOCK、BMAL1、PER1、CRY1 和 CRY2mRNA 水平降低。此外,HbA1c 水平与 BMAL1、PER1 和 CRY1mRNA 水平呈负相关。与对照组相比,糖尿病患者的 IL-6、TNF-α 和 CRP 水平更高。昼夜节律钟基因表达受损与血浆 IL-6 和 TNF-α 水平升高有关。此外,多元线性回归显示,血浆 IL-6 水平与昼夜节律钟基因表达受损相关。

结论

DT2 患者外周血白细胞中的昼夜节律钟基因减少。此外,昼夜节律钟基因表达受损与血浆炎症标志物水平升高有关。

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