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最新研究發現，高血糖不僅增加動脈血栓形成的風險，還會導致內皮細胞糖壁的顯著損失。這種糖壁的損失與內皮功能障礙和凝血活化密切相關，從而增加血管脆弱性。研究中發現，N-乙酰半胱氨酸（NAC）能有效預防高血糖對糖壁的損害，提供了防治高血糖引起血管問題的新思路。
急性高血糖期間，內皮細胞糖壁的損失與內皮功能障礙和凝血活化相關聯。
Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo
Nieuwdorp M, van Haeften TW, Gouverneur MC, Mooij HL, van Lieshout MH, Levi M, Meijers JC, Holleman F, Hoekstra JB, Vink H, Kastelein JJ, Stroes ES. Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes. 2006 Feb;55(2):480-6. doi: 10.2337/diabetes.55.02.06.db05-1103. PMID: 16443784.
https://pubmed.ncbi.nlm.nih.gov/16443784/
Abstract
Hyperglycemia is associated with increased susceptibility to atherothrombotic stimuli. The glycocalyx, a layer of proteoglycans covering the endothelium, is involved in the protective capacity of the vessel wall. We therefore evaluated whether hyperglycemia affects the glycocalyx, thereby increasing vascular vulnerability. The systemic glycocalyx volume was estimated by comparing the distribution volume of a glycocalyx permeable tracer (dextran 40) with that of a glycocalyx impermeable tracer (labeled erythrocytes) in 10 healthy male subjects. Measurements were performed in random order on five occasions: two control measurements, two measurements during normoinsulinemic hyperglycemia with or without N-acetylcysteine (NAC) infusion, and one during mannitol infusion. Glycocalyx measurements were reproducible (1.7 +/- 0.2 vs. 1.7 +/- 0.3 l). Hyperglycemia reduced glycocalyx volume (to 0.8 +/- 0.2 l; P < 0.05), and NAC was able to prevent the reduction (1.4 +/- 0.2 l). Mannitol infusion had no effect on glycocalyx volume (1.6 +/- 0.1 l). Hyperglycemia resulted in endothelial dysfunction, increased plasma hyaluronan levels (from 70 +/- 6 to 112 +/- 16 ng/ml; P < 0.05) and coagulation activation (prothrombin activation fragment 1 + 2: from 0.4 +/- 0.1 to 1.1 +/- 0.2 nmol/l; d-dimer: from 0.27 +/- 0.1 to 0.55 +/- 0.2 g/l; P < 0.05). Taken together, these data indicate a potential role for glycocalyx perturbation in mediating vascular dysfunction during hyperglycemia.
摘要
高血糖與對於動脈血栓形成刺激的敏感性增加相關。糖壁是覆蓋內皮的一層蛋白聚糖，參與了血管壁的保護能力。因此，我們評估了高血糖是否影響糖壁，從而增加了血管的脆弱性。我們通過比較糖壁可滲透示蹤劑（40號葡聚糖）的分佈體積與糖壁不可滲透示蹤劑（標記的紅血球）的分佈體積來估算系統性的糖壁體積，該研究包括了10名健康男性受試者。測量在五個不同的場合進行，隨機順序進行：兩次對照測量，兩次在正常胰島素高血糖狀態下進行測量（是否注射N-乙酰半胱氨酸（NAC）），以及一次甘露醇注射。糖壁的測量具有可重復性（1.7 +/- 0.2 vs. 1.7 +/- 0.3升）。高血糖降低了糖壁體積（至0.8 +/- 0.2升；P < 0.05），而NAC能夠防止這種降低（1.4 +/- 0.2升）。甘露醇注射對糖壁體積無影響（1.6 +/- 0.1升）。高血糖導致內皮功能障礙，增加了血漿透明質酸水平（從70 +/- 6 ng/ml增加到112 +/- 16 ng/ml；P < 0.05），以及凝血活化（凝血酶原活化片段1 + 2：從0.4 +/- 0.1 nmol/l增加到1.1 +/- 0.2 nmol/l；D-二聚體：從0.27 +/- 0.1 g/l增加到0.55 +/- 0.2 g/l；P < 0.05）。綜上所述，這些數據表明，在高血糖期間，糖壁擾亂可能在調解血管功能障礙方面具有潛在作用。