Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
J Diabetes Complications. 2017 Oct;31(10):1538-1543. doi: 10.1016/j.jdiacomp.2017.07.005. Epub 2017 Jul 13.
Impaired anti-inflammatory ability of high-density lipoprotein (HDL) has been demonstrated in patients with type-2 diabetes mellitus (T2DM). However, whether HDL from patients with diabetic nephropathy (DN) suffers additional damage remains unknown. This study compared the anti-inflammatory capacities of HDL from healthy controls, T2DM patients with normal renal function, and T2DM patients with DN.
HDL was isolated from healthy controls (n=33) and T2DM patients with normal renal function (n=21), chronic kidney disease (CKD) (n=27), and end-stage renal disease (ESRD) (n=27). Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers were pretreated with HDL (100μg/mL) for 1h, then incubated with lipopolysaccharide (LPS) (50ng/mL) for 24h. The anti-inflammatory ability of HDL was measured as the secretion of TNF-α in LPS-activated monocytes.
The anti-inflammatory ability of HDL was gradually impaired as kidney function declined. Serum amyloid A (SAA) concentration in HDL significantly increased and was positively correlated with the impaired anti-inflammatory ability of HDL (Pearson r=0.315, P=0.006). Furthermore, HDL supplemented with SAA significantly increased TNF-α release from PBMCs compared with that from control HDL.
These findings identified an impaired anti-inflammatory capacity of HDL from DN patients, which might be attributable to SAA enrichment.
已有研究表明，2 型糖尿病（T2DM）患者的高密度脂蛋白（HDL）抗炎能力受损。然而，糖尿病肾病（DN）患者的 HDL 是否受到进一步损伤尚不清楚。本研究比较了健康对照者、肾功能正常的 T2DM 患者和 DN 患者的 HDL 的抗炎能力。
从健康对照者（n=33）和肾功能正常的 T2DM 患者（n=21）、慢性肾脏病（CKD）（n=27）和终末期肾病（ESRD）（n=27）患者中分离 HDL。用 HDL（100μg/mL）预处理健康志愿者外周血单个核细胞（PBMCs）1h，然后用脂多糖（LPS）（50ng/mL）孵育 24h。用 LPS 激活单核细胞后，通过 TNF-α 的分泌来测量 HDL 的抗炎能力。
随着肾功能下降，HDL 的抗炎能力逐渐受损。HDL 中的血清淀粉样蛋白 A（SAA）浓度显著增加，与 HDL 抗炎能力受损呈正相关（Pearson r=0.315，P=0.006）。此外，与对照 HDL 相比，补充 SAA 的 HDL 可显著增加 PBMCs 中 TNF-α 的释放。
这些发现表明 DN 患者的 HDL 抗炎能力受损，这可能归因于 SAA 的富集。
