摘要
目的:观察辛伐他汀(Sim)对大鼠骨骼肌线粒体膜流动性及ATP酶活性的影响。方法:大鼠口服给予3种不同剂量Sim,酶法测定丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)及肌酸激酶(CK)活性。以1-苯氨基萘-8-磺酸(ANS)、1,6-二苯基-1,3,5-己三烯(DPH)为荧光探针标记骨骼肌线粒体膜浅层及深层,测定骨骼肌线粒体膜荧光强度(F),荧光偏振度(P)及平均微黏度(-η)。比色法测定Na+-K+-ATP酶和Ca2+-Mg2+-ATP酶活性。结果:给予Sim3.6,7.2mg.kg-1.d-1组,血清ALT、AST、CK和骨骼肌线粒体膜Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶的活性均无显著变化。而给予Sim14.4mg.kg-1.d-1,血清CK活性显著增高,骨骼肌线粒体膜Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性则明显降低。给予Sim3.6,7.2,14.4mg.kg-1.d-1组,ANS标记的线粒体膜浅层和DPH标记的线粒体膜深层F、P、-η均明显降低,表明Sim可增加线粒体膜浅层及深层流动性。结论:Sim在高剂量时可导致骨骼肌细胞损伤,其机制可能与Sim能增加骨骼肌线粒体膜流动性,降低骨骼肌线粒体膜Ca2+-Mg2+-ATP酶及Na+-K+-ATP酶活性有关。
OBJECTIVE To investigate the effect of Simvastatin （Sim） on skeletal muscle mitochondrial membrane fluidity and ATPase activity in rats. METHODS ALT, AST and CK activities were determined with enzymology method. The external and internal membrane of skeletal muscle mitochondria were labeled by ANS and DPH. Membrane fluorescent intensity （F）, fluorescent polarization （P） and microviscosity （^η） of skeletal muscle mitochondria were determined. Na^＋ -K^＋ -ATPase and Ca^2＋ -Mg^2＋ -ATPase activity was determined with spectrophotometric method. RESULTS After oraladministration of Sim 3.6, 7. 2 mg·kg^-1·d^-1, serum ALT, AST, CK activities and Na^＋ -K^＋ -ATPase,Ca^2＋ -Mg^2＋ -ATPase of skeletal muscle mitochondria had no significant changes in rats, Sim 14. 4 mg·kg^-1·d^-1, ig, serum CK activity was obviously increased, Na^＋ -K^＋ - ATPase, Ca^2＋ -Mg^2＋ -ATPase of skeletal muscle mitochondria were remarkably decreased. After treatment with Sim 3.6, 7. 2, 14. 4 mg·kg^-1·d^-1 （ig）, membrane fluorescent intensity （F）, fluorescent polarization （P） and microviscosity （^-η） of the external and internal membrane of skeletal muscle mitochondria labeled by ANS and DPH were obviously decreased. It＇s indicated that fluidity of skeletal muscle mitochondrial membrane was increased. CONCLUSION Sim of high dose could cause skeletal muscle cell injury, the mechanism is related to increase in fluidity of skeletal muscle mitochondrial membrane and decrease in Na^＋ -K^＋ -ATPase, Ca^2＋ -Mg^2＋ -ATPase activities.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2007年第5期582-584,共3页
Chinese Journal of Hospital Pharmacy
基金
湖北省自然科学基金项目(编号:2003ABA174)
关键词
辛伐他汀
骨骼肌
线粒体
膜流动性
ATP酶
simvastatin
skeletal muscle
mitochondria
membrane fluidity
ATPase
