Rojas-Espinosa O, Becerril-Villanueva E, Wek-Rodríguez K, Arce-Paredes P, Reyes-Maldonado E
Departmento de Inmunología, Escuela Nacional de Ciencias Biologicas del Instituto Politecnico Nacional, Mexico DF.
Clin Exp Immunol. 2005 Jun;140(3):436-42. doi: 10.1111/j.1365-2249.2005.02776.x.
A small but relatively constant proportion (3-5%) of mice chronically infected with Mycobacterium lepraemurium (MLM) develops bilateral paralysis of the rear limbs. The aim of the study was to investigate whether or not the bilateral leg palsy results from nerve involvement. Direct bacterial nerve infection or acute/delayed inflammation might possibly affect the nerves. Therefore, palsied animals were investigated for the presence of: (a) histopathological changes in the leg tissues including nerves, bones and annexes, and (b) serum antibodies to M. lepraemurium and M. leprae lipids, including phenolic glycolipid I from M. leprae. Histopathological study of the palsied legs revealed that the paralysis was not the result of direct involvement of the limb nerves, as neither bacilli nor inflammatory cells were observed in the nerve branches studied. Antibodies to brain lipids and cardiolipin were not detected in the serum of the palsied animals, thus ruling out an immune response to self-lipids as the basis for the paralysis. Although high levels of antibodies to MLM lipids were detected in the serum of palsied animals they were not related to limb paralysis, as the nerves of the palsied legs showed no evidence of inflammatory damage. In fact, nerves showed no evidence of damage. Paralysis resulted from severe damage of the leg bones. Within the bones the bone marrow became replaced by extended bacilli-laden granulomas that frequently eroded the bone wall, altering the normal architecture of the bone and its annexes, namely muscle, tendons and connective tissue. Although this study rules out definitively the infectious or inflammatory damage of nerves in murine leprosy, it opens a new avenue of research into the factors that participate in the involvement or the sparing of nerves in human and murine leprosy, respectively.
一小部分但比例相对恒定（3% - 5%）的长期感染鼠麻风杆菌（MLM）的小鼠会出现后肢双侧麻痹。本研究的目的是调查双侧腿部麻痹是否由神经受累引起。直接的细菌神经感染或急性/迟发性炎症可能会影响神经。因此，对麻痹的动物进行了以下检查：（a）腿部组织（包括神经、骨骼和附属结构）的组织病理学变化，以及（b）针对鼠麻风杆菌和麻风杆菌脂质（包括来自麻风杆菌的酚糖脂I）的血清抗体。对麻痹腿部的组织病理学研究表明，麻痹并非肢体神经直接受累的结果，因为在所研究的神经分支中未观察到杆菌或炎性细胞。在麻痹动物的血清中未检测到针对脑脂质和心磷脂的抗体，从而排除了对自身脂质的免疫反应是麻痹的基础。尽管在麻痹动物的血清中检测到高水平的针对MLM脂质的抗体，但它们与肢体麻痹无关，因为麻痹腿部的神经未显示出炎性损伤的迹象。实际上，神经没有损伤迹象。麻痹是由腿部骨骼的严重损伤导致的。在骨骼内部，骨髓被充满杆菌的扩展性肉芽肿所取代，这些肉芽肿经常侵蚀骨壁，改变了骨骼及其附属结构（即肌肉、肌腱和结缔组织）的正常结构。尽管本研究明确排除了鼠麻风病中神经的感染性或炎性损伤，但它为分别参与人类和鼠类麻风病中神经受累或幸免的因素开辟了一条新的研究途径。
