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

远端空泡形成性肌病（DMRV）是近年来引起广泛关注的一种肌纤维变性疾病。在有边空泡内发现大量酸性磷酸酶，提示溶酶体在肌纤维变性中起重要作用。长期高剂量氯喹可引起大鼠空泡性肌病。组织化学观察发现，在大鼠空泡性肌病中，酸性磷酸酶大量积聚，和髓样小体的丰度，其基本上与DMRV相同。因此，我们用氯喹诱发大鼠DMRV模型，并联合应用半胱氨酸蛋白酶抑制剂，观察该药对氯喹肌病的防治作用，结果发现，氯喹50 mg/kg/d连续给药8周，大鼠出现以自噬杆状核形成和溶酶体酶，尤其是组织蛋白酶B升高为特征的氯喹肌病。用10 mg/kg/d的EST与氯喹同时口服，可防止氯喹肌病的诱发。用10 mg/kg/d的EST与氯喹注射，治疗已患氯喹肌病的大鼠5周后，其组织化学和生物化学也明显恢复。EST可能不仅对DMRV有益，而且对与自噬空泡相关的相关肌病也有益。

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.