Murrell G A
Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710.
Ann R Coll Surg Engl. 1992 May;74(3):156-60; discussion 161.
Dupuytren's contracture is a deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists since the early descriptions by Guillaume Dupuytren in 1831. It predominantly affects elderly, male caucasians, has a hereditary predisposition and has strong associations with diabetes, alcohol consumption, cigarette smoking and HIV infection. The major morphological features are an increase in fibroblasts, particularly around narrowed fibroblasts; a finding consistent with localised ischaemia. During ischaemia, adenosine triphosphate (ATP) is converted to hypoxanthine and xanthine, and endothelial xanthine dehydrogenase to xanthine oxidase (alcohol also mediates this change, a finding of particular relevance given the association of Dupuytren's contracture with alcohol intake). Xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and uric acid with the release of superoxide free radicals (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (OH.). These free radicals are highly reactive, with half-lives in the order of milliseconds and are toxic in high concentrations. A potential for free radical generation in Dupuytren's contracture was elicited by finding a sixfold increase in hypoxanthine concentrations in Dupuytren's contracture compared with control palmar fascia. In vitro studies affirmed the toxic effects of oxygen free radicals to Dupuytren's contracture fibroblasts, but also showed that, at lower concentrations (concentrations similar to those likely to occur in Dupuytren's contracture), free radicals had a stimulatory effect on fibroblast proliferation. Cultured fibroblasts were found to release their own O2-. These endogenously released free radicals were also found to be important in fibroblast proliferation. The collagen changes of Dupuytren's contracture were examined. The results established that fibroblast origin was unimportant, but that inhibition of type I collagen production at high fibroblast density accounted for the increase in type III/I collagen ratios observed by previous investigators. These biochemical and morphological observations throw new light on Dupuytren's contracture. They suggest that age, genetic and environmental factors may contribute to micro vessel narrowing with consequent localised ischaemia and free radical generation. Endothelial xanthine oxidase derived free radicals may both damage the surrounding stroma and stimulate fibroblasts to proliferate. Proliferating fibroblasts lay down and contract collagen in lines of stress.Progressive fibroblast proliferation and deposition of collagen is likely to encourage further microvessel narrowing with a positive feedback effect consistent with the progressive nature of the condition.
杜普伊特伦挛缩症是一种手掌筋膜的变形纤维化病症，自1831年纪尧姆·杜普伊特伦首次描述以来，一直困扰着临床医生和科学家。它主要影响老年白人男性，具有遗传易感性，并且与糖尿病、饮酒、吸烟和艾滋病毒感染密切相关。主要形态学特征是成纤维细胞增加，尤其是在狭窄的成纤维细胞周围；这一发现与局部缺血一致。在缺血期间，三磷酸腺苷（ATP）转化为次黄嘌呤和黄嘌呤，内皮黄嘌呤脱氢酶转化为黄嘌呤氧化酶（酒精也介导这种变化，鉴于杜普伊特伦挛缩症与酒精摄入的关联，这一发现具有特殊意义）。黄嘌呤氧化酶催化次黄嘌呤氧化为黄嘌呤和尿酸，并释放超氧自由基（O2-）、过氧化氢（H2O2）和羟基自由基（OH·）。这些自由基具有高度反应性，半衰期以毫秒计，高浓度时具有毒性。与对照手掌筋膜相比，杜普伊特伦挛缩症中次黄嘌呤浓度增加了六倍，这表明该病存在自由基生成的可能性。体外研究证实了氧自由基对杜普伊特伦挛缩症成纤维细胞的毒性作用，但也表明，在较低浓度（与杜普伊特伦挛缩症中可能出现的浓度相似）下，自由基对成纤维细胞增殖具有刺激作用。培养的成纤维细胞被发现会释放自身的O2-。这些内源性释放的自由基在成纤维细胞增殖中也很重要。对杜普伊特伦挛缩症的胶原蛋白变化进行了研究。结果表明，成纤维细胞的来源并不重要，但在高成纤维细胞密度下对I型胶原蛋白产生的抑制作用解释了先前研究人员观察到的III/I型胶原蛋白比例增加的现象。这些生化和形态学观察为杜普伊特伦挛缩症提供了新的见解。它们表明，年龄、遗传和环境因素可能导致微血管狭窄，进而导致局部缺血和自由基生成。内皮黄嘌呤氧化酶衍生的自由基可能既损害周围基质，又刺激成纤维细胞增殖。增殖的成纤维细胞在应力线上沉积并收缩胶原蛋白。成纤维细胞的逐渐增殖和胶原蛋白的沉积可能会进一步促使微血管狭窄，产生正反馈效应，这与该病的渐进性本质相符。
