Synergistic effects of cyclosporine and rapamycin in a chronic nephrotoxicity model
Synergistic effects of cyclosporine and rapamycin in a chronic nephrotoxicity model
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DOI：
10.1097/00007890-199608150-00002
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发表时间：
1996-08-15
期刊：
影响因子：
6.2
通讯作者：
Bennett, WM
中科院分区：
文献类型：
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作者：
Andoh, TF;Lindsley, J;Bennett, WM
雷帕霉素（Rapamycin， RAPA）与环孢素（cyclosporine, CsA）在多种器官移植和自身免疫性疾病动物模型中协同作用，实现了强大的免疫抑制作用，如果这两种药物联合使用，不应增加毒性，因此，我们研究了CsA和RAPA联合使用对慢性CsA肾病大鼠肾脏结构和功能的影响，大鼠分别给予安慰剂、CsA（2、4和8 mg/kg）、RAPA(0.01和0.1 mg/kg)，在低盐饮食中，0.1 mg/kg的亚治疗剂量的RAPA使葡萄糖代谢恶化，并在肾功能和结构损伤方面增强了8 mg/kg的CsA诱导的慢性肾毒性。由于已知高血糖会加速纤维化过程，葡萄糖代谢的损害可能在小管间质纤维化中发挥作用(血浆葡萄糖vs，小管间质纤维化，r=0.72, n=18， P
Rapamycin (RAPA) acts synergistically with cyclosporine (CsA) to achieve powerful immunosuppression in several animal models of organ transplantation and autoimmune disease, If these drugs are to be used together, they should not enhance toxicity, Thus, we examined the effects of combining CsA and RAPA on renal structure and function in a rat model of chronic CSA nephropathy, Rats were given placebo, CSA (2, 4, and 8 mg/kg), RAPA (0.01 and 0.1 mg/kg), or CsA+RAPA for 28 days while on a low-salt diet, RAPA at a subtherapeutic dose of 0.1 mg/kg worsened glucose metabolism and potentiated chronic nephrotoxicity induced by CsA at 8 mg/kg in terms of both renal function and structural injury, Since hyperglycemia is known to accelerate fibrotic processes, the impairment of glucose metabolism may play a role in tubulointerstitial fibrosis (plasma glucose vs, tubulointerstitial fibrosis, r=0.72, n=18, P