Yan Zheyi, Zhao Jianli, Gan Lu, Zhang Yanqing, Guo Rui, Cao Xiaoming, Lau Wayne Bond, Ma Xin, Wang Yajing
Department of Ophthalmology, The First Affiliated Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States of America.
PLoS One. 2017 Jun 20;12(6):e0178253. doi: 10.1371/journal.pone.0178253. eCollection 2017.
Diabetic retinopathy (DR) is a severe complication of chronic diabetes. The C1q/TNF-related protein family (CTRPs) has been demonstrated to exert protective effects against obesity and atherosclerosis in animal studies. Heretofore, the association between circulating CTRPs and DR patients has been unexplored. In the current study, we attempt to define this association, as well as the effect of CTRPs upon DR pathophysiology.
The present investigation is a case control study that enrolled control subjects and type 2 diabetes mellitus (T2DM) patients diagnosed with DR. Serum CTRPs and sVACM-1 were determined by ELISA.
Serum CTRP3 and CTRP5 levels were markedly decreased in patients with T2DM compared to controls (p<0.05) and inversely associated with T2DM. Furthermore, mutivariate regression and ROC analysis revealed CTRP3 deficiency, not CTRP5, was associated with proliferative diabetic retinopathy (PDR). Spearman's rank correlation assay demonstrated an inverse association between CTRP3 and sVCAM-1. Finally, exogenous CTRP3 administration attenuated high glucose high lipid (HGHL)-induced VCAM-1 production in an AMPK-dependent manner in cultured human retinal microvascular endothelial cells (HRMECs).
CTRP3 may serve as a novel biomarker for DR severity. CTRP3 may represent a future novel therapeutic against DR, a common ocular complication of diabetes.
糖尿病视网膜病变（DR）是慢性糖尿病的一种严重并发症。在动物研究中，C1q/TNF相关蛋白家族（CTRPs）已被证明对肥胖和动脉粥样硬化具有保护作用。迄今为止，循环CTRPs与DR患者之间的关联尚未得到探索。在本研究中，我们试图确定这种关联以及CTRPs对DR病理生理学的影响。
本研究是一项病例对照研究，纳入了对照受试者和被诊断为DR的2型糖尿病（T2DM）患者。通过ELISA测定血清CTRPs和sVACM-1。
与对照组相比，T2DM患者的血清CTRP3和CTRP5水平显著降低（p<0.05），且与T2DM呈负相关。此外，多变量回归和ROC分析显示，与增殖性糖尿病视网膜病变（PDR）相关的是CTRP3缺乏，而非CTRP5。Spearman等级相关分析表明CTRP3与sVCAM-1之间呈负相关。最后，在培养的人视网膜微血管内皮细胞（HRMECs）中，外源性给予CTRP3以AMPK依赖的方式减弱了高糖高脂（HGHL）诱导的VCAM-1产生。
CTRP3可能作为DR严重程度的一种新型生物标志物。CTRP3可能代表未来针对DR（糖尿病常见的眼部并发症）的一种新型治疗方法。
