骨髓增生异常综合征的免疫抑制方法

骨髓增生异常综合征 (ＭＤＳ)系由于造血干细胞本身因某种内因性异常而引起的无效造血、血细胞减少的综合征。治疗ＭＤＳ的唯一疗法是造血干细胞移植。然而 ,由于ＭＤＳ是高龄者的多发疾病 ,因此适应于移植的患者数极其有限。多数患者只能依靠投予蛋化同化激素、肾上腺皮质激素、Ｇ -ＣＳＦ等化学疗法进行治疗。而这些药物的有效性又很低 ,对重症患者只能依赖于输血的补充疗法。有报道提示本病的血细胞减少 ,有可能是由于免疫学机制所致 ,故最近相继开展了对ＭＤＳ的免疫抑制疗法。其治疗ＭＤＳ的现状介绍如下。一、环孢菌素Ａ(ＣｓＡ)疗法1…     

蚕砂提取物联合环孢菌素A治疗再生障碍性贫血的实验研究

目的:研究蚕砂提取物联合环孢菌素A治疗再障的作用机制。方法:建立免疫介导的小鼠再障模型,随机分为4组,每组10只。对照组胃饲生理水,SCC组胃饲SCC,CsA组胃饲CsA,SCC+CsA组胃饲SCC+CsA,连续胃饲13天,检测外周血象及外周血CD3+、CD4+、CD8+、TNF-α、IFN-γ、IL-6水平。结果:蚕砂提取物联合环孢菌素A灌胃,可提高小鼠外周血白细胞、血红蛋白、血小板,有效调节再障小鼠外周血CD3+、CD4+、CD8+、TNF-α、IFN-γ、IL-6水平。结论:蚕砂提取物联合环孢菌素A治疗再障具有协同增效作用。     

环孢菌素A的临床应用

环孢菌素A(cyclosporin A, CsA)是1972年发现的一种新型免疫抑制剂,其化学成分为8种氨基酸组成的环形多肽,分子量1203,易溶于油性溶媒和乙醇,能特异性地抑制辅助性T细胞的效应和毒效T细胞的产生,但对抑制性T细胞活性和增殖无影响;它还能选择性抑制辅助性T组胞产生和/或释放     

环孢素A肾中毒9例分析

目的：探讨环孢素A肾中毒诊断和治疗。方法：对9例经移植肾穿刺病理检查诊断环孢素A肾中毒。治疗上给予环孢素A减量或停用,增加百令胶囊用量,静脉滴注丹参注射液。结果：本组有7例移植肾功能恢复正常,2例肾功能改善。结论：环孢素A肾毒性是其主要副作用,通过减少或停用环孢素A,加用丹参注射液,是改善环孢素A肾损害的有效方法。     

低蛋白饮食对环孢素A肾病大鼠肾间质纤维化的作用

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with C group, the serum cholesterol levels in M and I groups were significantly increased (P<0.05), and the serum phosphorus level in I group was significantly decreased (P<0.05). The levels of serum albumin and serum calcium of all three groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.     

我国肾移植患者环孢菌素常规监测的群体药代动力学

目的考察肾移植患者口服环孢菌素A(Cyclosporine A,CsA)常规监测的群体药代动力学特征,为临床调整个体用药提供新途径.方法回顾性收集我院745例门诊肾移植病人的1468个全血稳态谷浓度样本,用NONMEM程序分析其群体药物动力学模型,估算米-曼氏模型参数Km和Vm,Km,Vm的个体间变异,以及个体自身变异采用指数模型.定量地考察日剂量、术后时间、体重、环孢菌素A剂型和合并用药等固定效应对药物动力学参数的影响.结果环孢菌素A的监测值为稳态谷浓度时,其药代动力学能用米-曼氏模型较好地拟合,用建模组数据获得的群体参数在验证组中有较理想的拟合优度.最终群体药代动力学参数为群体标准值Vm为601mg@L-1,Km为2120mg@L-1.Vm的结构模型参数术后时间和体重用指数模型,系数分别为-0.210和0.1 39;性别和剂型用乘法模型,男性较女性的校正系数为1.078,胶囊剂较水剂的校正系数为0.927.Km的结构模型参数剂量和术后时间用指数模型,系数分别为-1.67和-0.651;合并应用雷公藤多甙片、保肾片用乘法模型,系数分别为1.170、1.1 30.每日剂量预测值与观察值的平均绝对百分误差为7.72±6.60%.结论剂量和术后时间对米-曼模型的参数拟合有非常明显的影响.本文估算的参数误差在相对较小的范围内,模型拟合情况较好,可以为临床上制定合理的用药方案服务.     

亲免素结合类免疫抑制剂作用的分子机理

随着环孢素、FK5 0 6及雷帕霉素等生物制剂类免疫抑制剂在器官移植时的免疫抑制及治疗自身免疫性疾病的成功应用 ,对其生物作用机理有了一定认识。发现了生物体内存在其天然配基亲免素 ,并通过形成药物 亲免素复合物发挥免疫抑制作用 ,故又称为亲免素结合类免疫抑制剂。近年来研究证实 ,药物 亲免素复合物分别作用于细胞信号传递体系中的钙调磷酸酶与雷帕霉素靶蛋白 ,从而影响免疫细胞的蛋白质生物合成 ,细胞的增殖和生存 ,达到免疫抑制的作用。     

全血中环孢菌素A分析方法进展

环孢菌素Ａ(ｃｙｃｌｏｓｐｏｒｉｎｅＡ，ＣｙＡ)是一种由１１种氨基酸组成的环状多肽化合物 ,具有亲脂性 ;它是由真菌———多孢子木霉培养而产生的代谢物再经提取而得 ,１９７２年发现它具有显著的免疫抑制作用 ,于１９７８年首次用于临床 ,国内外均用于肾、肝、心、肺及骨髓移植中克服受移植者对植入器官排斥反应或移植物对宿主引起的疾病。近年来 ,ＣｙＡ在眼科手术上亦得到广泛的应用 ,还用于治疗自身免疫性疾病。由于ＣｙＡ体内过程个体差异大 ,治疗窗窄 ,其血药浓度过高会引起毒副反应 ,尤其是对肝、肾的毒性 ,因此在治疗过程中进行…