Chloroquine myopathy,its mechanism and treatment with cysteine proteinase inhibitor,EST

近年来，远端肌病伴脑空泡形成（DMRV）的研究受到了广泛的关注。高酸性磷酸酶在边缘液泡中的存在强烈提示溶酶体在肌纤维变性中的作用。据报道，长期给药大剂量氯喹可引起大鼠空泡性肌病。组织化学检查显示酸性磷酸酶的积累，以及与DMRV基本相同的髓样体的丰富。因此，我们在大鼠身上制作了氯喹肌病作为DMRV模型，并联合给药一种强效半胱氨酸蛋白酶抑制剂EST，观察该药物是否能预防和治疗氯喹肌病。给大鼠50mg/kg/天氯喹8周后，产生以自噬杆状孔形成和溶酶体酶（尤其是组织蛋白酶B和l）升高为特征的氯喹性肌病。已患氯喹性肌病的大鼠给予EST 10mg/kg/天，同时给予氯喹注射5周。肌病的组织化学和生物化学指标均有明显的恢复。因此，EST可能不仅对DMRV有益，而且对与自噬空泡相关的肌病也有益。

Recently much attention has been paid to distal myopathy with remmed vacule formation (DMRV).The presence of high acid phosphatase in rimmed vacuole strongly suggests the role of lysosome in muscle fiber degeneration.It was reported that long-term administration of high dosis of chloroquine caused vacuolar myopathy in rats.Histochemical investigation revealed an accumulation of acid phosphatase,and abundance of myeloid bodies which are essentially the same as DMRV. So,we have produced the chloroquine nyopathy in rats as a model of DMRV and coadministered a potent cysteine protease inhibitor,EST whether this druh could prevent and treat the chloroquine myopathy.The administration of 50mg/kg/day of chloroquine to rats for 8 weeks produced the chloroquine myopathy characterized by autophagic bacuole formation and increase in lysosomal enzymes,especially cathepsins B,and L.Coadministration of 10mg/kg/day of EST by oral route and chloroquine prevented the induction of the chloroquine myopathy.Rats already suffered from the chloroquine myopathy were treated with 10mg/kg/day of EST together with chloroquine injections for 5 weeks.They also recovered remarkably from the myopathy,histochemically and biochemically.Thus, EST may be beneficial for not only DMRV but also related myopathies associated with autophagic vacuoles.