Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Chem Biol Interact. 2010 Apr 15;185(1):53-8. doi: 10.1016/j.cbi.2010.02.029. Epub 2010 Feb 24.
Cyclosporine (CsA) is an immunosuppressive agent frequently used in the clinic for prevention of allograft rejection and for the treatment of autoimmune diseases. Despite its desired action on the immune system, CsA treatment may present serious adverse effects, which are masked by the concomitant use of other drugs. The search for effective immunosuppression protocols which does not affect the quality of life of patients is driving research to investigate the CsA involvement in vascular diseases, frequent in patients under immunosuppression. Thus, 45 non-transplanted Wistar rats were treated for 8 weeks with vehicle or 5 or 15 mg/kg CsA (n=15/group) by gavage administration to evaluate the specific influence of cyclosporine on the levels of risk factors (metabolic and inflammatory) of vascular disease and its mechanism of action. Therefore, serum insulin levels, glucose tolerance test, serum lipids profile, total homocysteine and fibrinogen levels were assessed. The biochemical alterations reported here suggest the development of a framework straight to diabetes. Glucose homeostasis was affected as indicated by decreased insulin levels and altered glucose tolerance test in CsA 15 mg/kg group compared to other groups. Serum insulin and total homocysteine levels presented a significant negative correlation (R=- 0.76, P<0.0001). Fibrinogen and serum lipids profiles were significantly increased in CsA 15 mg/kg group compared to other groups and correlated positively with total homocysteine levels. Considering the well-established correlation among insulin resistance, lipid and total homocysteine levels, hypercoagulability and atherosclerosis, we can assume that this protocol of long-term CsA treatment in non-transplanted rats alter biochemical parameters related to cardiovascular and cerebrovascular risk, mainly in CsA 15 mg/kg group. Insulin and tHcy serum levels appear to be central in this process.
环孢素（CsA）是一种常用于临床的免疫抑制剂，用于预防移植物排斥反应和治疗自身免疫性疾病。尽管它对免疫系统有理想的作用，但 CsA 治疗可能会产生严重的不良反应，这些不良反应被同时使用的其他药物所掩盖。寻找不影响患者生活质量的有效免疫抑制方案的研究正在推动研究，以调查 CsA 对免疫抑制患者常见的血管疾病的影响。因此，45 只非移植 Wistar 大鼠通过灌胃给予载体或 5 或 15mg/kg CsA（每组 15 只）治疗 8 周，以评估环孢素对血管疾病风险因素（代谢和炎症）水平的具体影响及其作用机制。因此，评估了血清胰岛素水平、葡萄糖耐量试验、血清脂质谱、总同型半胱氨酸和纤维蛋白原水平。这里报道的生化改变表明糖尿病的发病机制直接受到影响。与其他组相比，CsA 15mg/kg 组的葡萄糖稳态受到影响，表现为胰岛素水平降低和葡萄糖耐量试验改变。血清胰岛素和总同型半胱氨酸水平呈显著负相关（R=-0.76，P<0.0001）。与其他组相比，CsA 15mg/kg 组的纤维蛋白原和血清脂质谱显著增加，与总同型半胱氨酸水平呈正相关。考虑到胰岛素抵抗、脂质和总同型半胱氨酸水平、高凝状态和动脉粥样硬化之间的既定相关性，我们可以假设这种非移植大鼠长期 CsA 治疗方案改变了与心血管和脑血管风险相关的生化参数，特别是在 CsA 15mg/kg 组。血清胰岛素和 tHcy 水平似乎在这个过程中起着核心作用。
