Cuoco Lucio, Vescovo Giorgio, Castaman Roberto, Ravara Barbara, Cammarota Giovanni, Angelini Annalisa, Salvagnini Mario, Dalla Libera Luciano
Gastroenterology and Internal Medicine Unit, S. Bortolo Hospital, Vicenza, Italy.
Int J Cardiol. 2008 Jul 4;127(2):219-27. doi: 10.1016/j.ijcard.2007.06.006. Epub 2007 Aug 10.
Lean body mass wastage in active Crohn's disease is not only related to malnutrition, but also to local and systemic inflammation. Altered bowel permeability can represent a source of pro-inflammatory cytokines, that have been shown to produce muscle wastage by several mechanisms such as apoptosis. In our study we have evaluated the body composition and the pathological changes of skeletal muscle in patients with Crohn's disease to see whether a relationships between altered gut permeability, proinflammatory cytokines production and muscle wastage existed.
Thirteen consecutive steroid-free patients with active Crohn's disease underwent evaluation of body composition, sugar test for intestinal permeability, determination of serum levels of TNF-alpha, sphingosine, bacterial lipopolysaccaride, and biopsy of gastrocnemius. In bioptic samples we determined fibres cross sectional area, distribution of myosin heavy chains and apoptosis. Twenty healthy subjects formed the control group.
In patients lean body mass was reduced and intestinal permeability increased (p<0.01 for both). TNFalpha, sphingosine and lipopolysaccaride were increased (p<0.01). Fibres size was reduced (p<0.01), with shift of Myosin Heavy Chains from the slow to the fast type. Apoptosis was found in 5 patients' biopsies, never in controls.
Crohn's patients have a myopathy characterized by myocyte apoptosis, modifications of myosin and muscle atrophy. TNF-alpha and sphingosine, that are increased because of the enhanced lipopolysaccaride concentration due to altered gut permeability, may play a pathophysiological role in the development of this myopathy.
活动性克罗恩病患者的瘦体重消耗不仅与营养不良有关，还与局部和全身炎症有关。肠道通透性改变可能是促炎细胞因子的一个来源，这些细胞因子已被证明可通过多种机制（如细胞凋亡）导致肌肉消耗。在我们的研究中，我们评估了克罗恩病患者的身体组成和骨骼肌的病理变化，以观察肠道通透性改变、促炎细胞因子产生与肌肉消耗之间是否存在关联。
连续13例无类固醇治疗的活动性克罗恩病患者接受了身体组成评估、肠道通透性糖试验、血清肿瘤坏死因子-α（TNF-α）、鞘氨醇、细菌脂多糖水平测定以及腓肠肌活检。在活检样本中，我们测定了纤维横截面积、肌球蛋白重链分布和细胞凋亡情况。20名健康受试者组成对照组。
患者的瘦体重降低，肠道通透性增加（两者均p<0.01）。TNF-α、鞘氨醇和脂多糖水平升高（p<0.01）。纤维大小减小（p<0.01），肌球蛋白重链从慢型向快型转变。在5例患者的活检中发现细胞凋亡，对照组未发现。
克罗恩病患者存在一种以肌细胞凋亡、肌球蛋白改变和肌肉萎缩为特征的肌病。由于肠道通透性改变导致脂多糖浓度升高，进而升高的TNF-α和鞘氨醇可能在这种肌病的发生发展中起病理生理作用。
