Edwards B D, Bhatnagar D, Mackness M I, Gokal R, Ballardie F W, Chalmers R J, Durrington P N
University Department of Medicine, Manchester Royal Infirmary.
QJM. 1995 Feb;88(2):109-13.
The benefits of using cyclosporin in organ transplantation to prevent graft rejection outweigh its potential disadvantages, but with the use of low-dose cyclosporin in relatively healthy individuals, such as those with psoriasis, the risk:benefit ratio is altered. The effects of low-dose cyclosporin (< 5 mg/kg body weight) on liver function and serum lipids and lipoproteins were examined in 40 normolipidaemic, normotensive psoriasis patients with normal renal function. After 3 months of treatment, serum cholesterol and bilirubin concentrations and alkaline phosphatase activity increased significantly (p = 0.001), and glomerular filtration rate (GFR) declined from 107 to 96 ml/min/1.73 m2 (p = 0.05). All these values returned to pretreatment levels 3 months after cessation of cyclosporin. In 15 patients in whom lipoproteins were isolated by ultracentrifugation, there was an increase in plasma low-density lipoprotein (LDL) cholesterol (p = 0.05), but very-low-density lipoprotein cholesterol, high-density lipoprotein (HDL) and HDL2 and HDL3 cholesterol concentrations did not change. The increases in serum bilirubin, alkaline phosphatase activity and LDL cholesterol, seen in individuals with normal baseline liver and renal function, which reverted to baseline following cessation of cyclosporin, suggest that cyclosporin-induced hypercholesterolaemia may be due to either decreased biliary excretion of cholesterol or impaired catabolism of LDL.
在器官移植中使用环孢素预防移植物排斥反应的益处超过了其潜在的不利之处,但是在相对健康的个体(如银屑病患者)中使用低剂量环孢素时,风险效益比会发生改变。在40名肾功能正常、血脂正常且血压正常的银屑病患者中,研究了低剂量环孢素(<5mg/kg体重)对肝功能、血清脂质和脂蛋白的影响。治疗3个月后,血清胆固醇、胆红素浓度及碱性磷酸酶活性显著升高(p=0.001),肾小球滤过率(GFR)从107降至96ml/min/1.73m²(p=0.05)。停用环孢素3个月后,所有这些值均恢复至治疗前水平。在15名通过超速离心分离脂蛋白的患者中,血浆低密度脂蛋白(LDL)胆固醇升高(p=0.05),但极低密度脂蛋白胆固醇、高密度脂蛋白(HDL)以及HDL2和HDL3胆固醇浓度未发生变化。在基线肝功能和肾功能正常的个体中观察到的血清胆红素、碱性磷酸酶活性和LDL胆固醇升高,在停用环孢素后恢复至基线水平,这表明环孢素诱导的高胆固醇血症可能是由于胆固醇胆汁排泄减少或LDL分解代谢受损所致。