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

近些年来，远端肌病合并空泡形成引起了广泛的关注。在有边框的空泡中发现的高酸性磷酸酶强烈提示溶酶体在肌纤维退行性变中的作用。据报道，长期服用高剂量的氯喹可引起大鼠的空泡性肌病。组织化学研究显示，酸性磷酸酶的积聚和丰富的髓样小体与DMRV基本相同。因此，我们建立了大鼠氯喹肌病的DMRV模型，并联合应用了一种有效的半胱氨酸蛋白酶抑制剂EST，以确定该药是否能预防和治疗氯喹肌病。给大鼠灌胃50 mg/kg/d的氯喹8周后，出现了以自噬杆状细胞形成和溶酶体酶，尤其是组织蛋白酶B和L的增加为特征的氯喹肌病。口服EST 10 mg/kg/d和氯喹10 mg/kg/d联用可抑制氯喹肌病的诱导。已患氯喹肌病的大鼠经10 mg/kg/d的EST和氯喹注射治疗5周后，肌病明显恢复。因此，EST不仅对DMRV有益，而且对与自噬空泡相关的肌病也是有益的。

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.