Friedman D W, Boyd C D, Norton P, Greco R S, Boyarsky A H, Mackenzie J W, Deak S B
Department of Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick.
Ann Surg. 1993 Dec;218(6):754-60. doi: 10.1097/00000658-199312000-00009.
The aim of this study was to determine if alterations in fibrillar collagen synthesis were associated with the development of inguinal hernias.
Previous work has suggested that alterations in connective tissue accumulation may play a functional role in the development of inguinal hernias. In particular, several investigators have suggested that alterations in collagen synthesis, causally related to connective disorders such as osteogenesis imperfecta, may also be responsible for the inguinal herniation that is markedly increased in such patients. This study was undertaken therefore to study collagen synthesis in patients with inguinal hernia in the absence of any other connective tissue disease.
Skin fibroblasts from 9 patients with hernias and 15 control individuals were radiolabeled with 3H-proline. Trypsin-chymotrypsin-resistant type I and III collagens were isolated and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and recovery was quantified by laser densitometry. Steady-state levels of alpha 1(I) and alpha 1(III) procollagen mRNAs were also determined by northern and slot-blot hybridization analysis.
The alpha 1(I)/alpha 1(III) collagen ratios were shown to be 6.3 +/- 0.34 in fibroblasts from control individuals and 3.0 +/- 0.25 in fibroblasts from patients with inguinal hernias. This statistically significant difference (p < 0.0001) was caused by an increase in the secretion of alpha 1(III) procollagen from the fibroblasts of patients with hernias. A concomitant increase in the steady-state levels of alpha 1(III) procollagen mRNA was observed in total RNA isolated from the patients' fibroblasts.
A constitutive and systemic increase in type III collagen synthesis may result in reduced collagen fibril assembly in the abdominal wall, eventually leading to the development of herniation. Although it is not yet clear what genetic factors are responsible for the elevation in type III collagen synthesis in patients with hernias, this study represents the first attempt to define individuals with an abnormality in collagen production that may be specifically related to herniation. A clearer understanding of the possible genetic factors that influence the pathophysiology of this disease will be important to improve the treatment of patients in whom inguinal hernias develop.
本研究旨在确定纤维状胶原蛋白合成的改变是否与腹股沟疝的发生有关。
先前的研究表明，结缔组织积累的改变可能在腹股沟疝的发生中起作用。特别是，一些研究人员认为，与诸如成骨不全等结缔组织疾病因果相关的胶原蛋白合成改变，也可能是此类患者腹股沟疝明显增加的原因。因此，本研究旨在研究无任何其他结缔组织疾病的腹股沟疝患者的胶原蛋白合成情况。
对9例疝患者和15例对照个体的皮肤成纤维细胞用3H-脯氨酸进行放射性标记。分离抗胰蛋白酶-糜蛋白酶的I型和III型胶原蛋白，通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳进行分析，并用激光密度测定法定量回收率。还通过Northern和狭缝印迹杂交分析确定α1(I)和α1(III)前胶原mRNA的稳态水平。
对照个体成纤维细胞中的α1(I)/α1(III)胶原蛋白比率显示为6.3±0.34，腹股沟疝患者成纤维细胞中的比率为3.0±0.25。这种统计学上的显著差异（p<0.0001）是由于疝患者成纤维细胞中α1(III)前胶原分泌增加所致。在从患者成纤维细胞中分离的总RNA中观察到α1(III)前胶原mRNA的稳态水平同时增加。
III型胶原蛋白合成的组成性和全身性增加可能导致腹壁胶原纤维组装减少，最终导致疝的发生。虽然尚不清楚哪些遗传因素导致疝患者III型胶原蛋白合成升高，但本研究首次尝试确定胶原蛋白产生异常且可能与疝形成具体相关的个体。更清楚地了解影响该疾病病理生理学的可能遗传因素，对于改善腹股沟疝患者的治疗将具有重要意义。
