Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds
Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds
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DOI：
10.1042/cs20050026
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发表时间：
2005-07-01
期刊：
影响因子：
6
通讯作者：
Thornalley, PJ
中科院分区：
文献类型：
--
作者：
Berlanga, J;Cibrian, D;Thornalley, PJ
糖尿病中MG（甲基乙二醛）和相关蛋白糖基化的形成增加与糖尿病血管并发症的发生有关。糖尿病也与伤口愈合受损有关。在本研究中，我们研究了大鼠长期暴露于MG（5075 mg/kg体重）是否会导致伤口愈合和糖尿病样血管损伤受损。与生理盐水对照组相比，MG治疗可抑制生长、增加血清肌酸酐、诱导高胆固醇血症（均P < 0.05）和血管扩张不良（P < 0.01）。皮肤微血管内皮细胞减少，基底膜增厚，管腔闭塞。急性肉芽组织表现为不成熟（P < 0.01），并伴有再生细胞浸润受损和增殖率降低（P < 0.01）。免疫组织化学染色表明血管结构、皮肤组织和周围神经纤维中存在AGEs（晚期糖基化终产物）。PAGE（AGEs受体）的表达似乎在皮肤血管系统中增加。还有促炎和促纤维化反应，包括完整表皮中IL-1 β（白细胞介素-1 β）表达增加，血管生成区域中TNF-α（肿瘤坏死因子-α）表达增加，动脉中层中CTGF（结缔组织生长因子）表达增加，肾小球簇、肾小管上皮细胞和间质内皮细胞中TGF-β（转化生长因子-β）表达增加。我们的结论是，暴露于增加MG在体内与发病的微血管损伤和其他糖尿病样并发症在正常血糖的情况下。
Increased formation of MG (methylglyoxal) and related protein glycation in diabetes has been linked to the development of diabetic vascular complications. Diabetes is also associated with impaired wound healing. In the present study, we investigated if prolonged exposure of rats to MG (5075 mg/kg of body weight) induced impairment of wound healing and diabetes-like vascular damage. MG treatment at-rested growth, increased serum creatinine, induced hypercholesterolaemia (all P < 0.05) and irripaired vasodilation (P < 0.01) compared with saline controls. Degenerative changes in cutaneous microvessels with loss of endothelial cells, basement membrane thickening and luminal occlusion were also detected. Acute granulation appeared immature (P < 0.01) and was associated with an impaired infiltration of regenerative cells with reduced proliferative rates (P < 0.01). Immunohistochemical staining indicated the presence of AGEs (advanced glycation end-products) in vascular structures, cutaneous tissue and peripheral nerve fibres. Expression of PAGE (receptor for AGEs) appeared to be increased in the cutaneous vasculature. There were also pro-inflammatory and profibrotic responses, including increased IL-1 beta(interleukin-1 beta) expression in intact epidermis, TNF-alpha (tumour necrosis factor-a) in regions of angiogenesis, CTGF (connective tissue growth factor) in medial layers of arteries, and TGF-beta (transforming growth factor-beta) in glomerular tufts, tubular epithelial cells and interstitial endothelial cells. We conclude that exposure to increased MG in vivo is associated with the onset of microvascular damage and other diabetes-like complications within a normoglycaemic context.