环孢霉素A治疗Ⅴ型狼疮性肾炎的研究

目的Ⅴ型狼疮性肾炎(WHO分型LN-V型)主要表现为蛋白尿或肾病综合征,本文分析环孢霉素A(CsA)对LN-V型的疗效。方法分析16例经肾活检明确诊断为LN-V型患者CsA治疗的近期及远期的治疗反应。16例患者治疗前均处于肾病综合征状态。治疗方法CsA 5 mg／(kg·d)诱导治疗3个月,以后每月减1mg／(kg·d)直至2mg／(kg·d)维持,CsA治疗同时采用强的松维持。总疗程12～24月,随访时间18月～4年。结果诱导期CsA平均血药谷浓度为185±30.8μg／L。经CsA治疗3个月后,4例(25％)缓解,6例(37.5％)部分缓解。治疗6个月,平均尿蛋白为0.3±0.4g／24h,血清白蛋白为40.7±4.9g／L。12例(75％)缓解,3例(18.7％)部分缓解,1例(6.3％)无效,总有效率达93.7％。8例伴有镜下血尿者有6例血尿消失,血清学指标也有所改善。CsA停药两年后有5例(41.7％)复发。CsA治疗1月内81.2％患者(13／16)血尿素氮和肌酐有一过性升高。其它副作用有血压升高(6／16),少数患者出现多毛及齿龈增生。3例重复肾活检未见条索状间质纤维化或典型CsA导致的小动脉病变。结论本研究证实CsA治疗降低V型LN蛋白尿短期内疗效肯定,且CsA≤5mg／(kg·d)用于肾功能正常LN患者未出现严重肾毒性。但停用CsA后复发率高。CsA治疗V型LN的长期疗效及安全性有待严格的临床对照研究和随访。     

环孢霉素A治疗狼疮性肾炎并发急性肾衰

1　病情摘要1.1　病史　患者女性 ,4 1岁 ,因浮肿、蛋白尿 8个月 ,加重 1个月 ,少尿 5天入院。患者于 8个月前 ( 1999年 9月 )无明显诱因出现面部及双下肢浮肿 ,伴有反复口腔溃疡。查尿蛋白2 ～ 3 ,ＯＢ 2 ,予雷公藤多甙 2 0ｍｇ 3/ｄ治疗 1周 ,尿检异常无改善 ,自行停用。 1999年 10月至2 0 0 0年 3月每日服中药汤剂 (成份不明 ) ,亦无明显疗效。其间查Ｈｂ 84ｇ/Ｌ ,ＷＢＣ 2 8× 10 9/Ｌ。入院前6周无明显诱因出现浮肿加重 ,尿量减少 ( 10 0 0ｍｌ/ｄ左右 ) ,血压增高 2 5 3/ 14 7ｋＰａ( 190 / 110ｍｍＨｇ)。查尿蛋白 4 0 5ｇ/ 2 4…     

环孢霉素A治疗原发性肾病综合征

环孢霉素A(Cyclosporin A,CsA)是一种新型的免疫抑制剂,广泛应用于器官移植,抑制免疫排斥反应。1978年Calne等首次用于治疗原发性肾病综合征(PNS),并取得一定疗效. 一、药代动力学 CsA个体药代动力学差异较大,导致临床上个体用药剂量,药效及毒性不同.CsA具有高度脂溶性,有口服及静脉制剂。用药后3～6小时在血中达峰值,主要分布于红细胞及血浆中。CsA半衰期个体差异较大,健康人平均为8.4小时(RIA),肾衰病人为16.1小时(RIA).主要经胆道排泄,仅6%从尿中排出,其中0.1%为药物原型。 Fallath等实验观察发现,肾衰病人对CsA的     

环孢霉素A肾毒性

１　病例报告１．１　【病例１】　男性患者，３０岁，因肾移植术后１个月，肾功能延迟恢复，于１９９９０２２３入院。缘于１９９０年２月无诱因出现双下肢浮肿，尿检蛋白３＋，隐血＋，未予正规治疗，１９９６年４月发现血压升高达２０／１２ｋＰａ（１５０／９０ｍｍＨｇ），复查血清肌酐（ＳＣｒ）１７６μｍｏｌ／Ｌ。在我院行肾活检确诊为ＩｇＡ肾炎（组织学类型符合局灶性节段性肾小球硬化），给予降压、纠正酸中毒、保肾等综合治疗。１９９８年９月疲劳后头昏、恶心加重伴呕吐，尿量减少，ＳＣｒ升至８００μｍｏｌ／Ｌ以上，诊…     

环孢霉素A治疗小儿难治性肾病中环孢霉素亲和素基因表达的临床意义

目的：研究难治性肾病患儿ＣｓＡ治疗前后环孢霉素亲和素（ＣｙＰ）ｍＲＮＡ的表达及ＣｓＡ的浓度与ＣｙＰｍＲＮＡ基因表达之间的关系，探讨ＣｙＰ在儿童难治性肾病中的临床意义。方法：用ＣｓＡ５ｍｇ／（ｋｇ．ｄ）治疗２６例，其中１６例用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）法测定了治疗前后血白细胞中ＣｙＰｍＲＮＡ的基因表达，并以正常儿童作对照及测定ＣｓＡ血浓度。结果：难治性肾病患儿用ＣｓＡ治疗前血白细胞中ＣｙＰｍＲＮＡ基因表达明显高于治疗后和对照组，而ＣｓＡ血浓度与ＣｙＰｍＲＮＡ基因表达之间成负相关关系。结论：低浓度的ＣｓＡ与高水平表达的ＣｙＰ对肾病不能起到治疗作用，而ＣｓＡ血浓度在１００～２００μｇ／Ｌ之间与低水平表达的ＣｙＰ有助于肾病的缓解。     

环孢霉素A在系统性红斑狼疮治疗中的应用

本文就选择性免疫抑制剂环孢霉素 A(CyA)对系统性红斑狼疮(SLE)各临床症候、实验室检查结果的影响作一综述。并对 CyA 的用药方案及副反应作了相应介绍,阐述其在 SLE 治疗中的可能机理,评价 CyA 在 SLE 治疗中的地位。     

环磷酰胺冲击疗法对狼疮性肾炎患者血清白介素-6水平的影响

狼疮性肾炎(ｌｕｐｕｓｎｅｐｈｒｉｔｉｓ,ＬＮ)主要免疫异常特征是Ｂ细胞内源性多克隆激活而产生大量免疫球蛋白和自身抗体,Ｂ细胞过度激活的原因未明;另外,大剂量环磷酰胺静脉给药(ＩＶＣＴＸ)治疗ＬＮ在稳定肾功能、减少复发和改善预后等方面有独特疗效[1],但ＩＶＣＴＸ的作用机制尚不明确,为此我们检测了42例ＬＮ患者血清白细胞介素6(ＩＬ6)水平及ＩＶＣＴＸ治疗前后ＩＬ6的变化。1　对象和方法1.1　对象　据症状、血沉、免疫学、尿液、肾功能及病理学检查综合判断42例ＬＮ的活动情况,其中活动期ＬＮ22例,非活动期ＬＮ20例,健康对照组2…     

狼疮性肾炎患者血清IL-6和sIL-2R水平变化的检测

目的探讨狼疮性肾炎(LN)患者血清中白细胞介素(IL)-6和可溶性IL-2受体(sIL-2R)的水平变化及临床意义。方法利用酶联免疫吸附试验(ELISA)检测42例LN患者和40例正常健康人血清IL-6和sIL-2R的水平。结果活动期LN组患者IL-6和sIL-2R水平显著高于静止期LN组患者及正常对照组(P<0.01),静止期LN组患者IL-6和sIL-2R水平显著高于正常对照组,差异有显著性(P<0.01)。结论LN患者血清IL-6和sIL-2R显著升高,可能与LN的发生发展有关,并可作为病情及疗效判断的观察指标。     

Prospective study of low-dose cyclosporine A in patients with refractory lupus nephritis

We evaluated the efficacy and safety of low-dose cyclosporine A (CsA) in patients with refractory lupus nephritis. Nine patients with systemic lupus erythematosus who had lupus nephritis resistant to previous treatment with glucocorticoids and immunosuppressants other than CsA were enrolled in a prospective, open-label study. All patients initially received 2.5 mg/kg per day of CsA; the dosage was adjusted to reach a blood trough level of 80–150 ng/ml. The urinary protein concentration decreased significantly 2 weeks after the initiation of treatment. After 30 weeks of CsA treatment, the mean urinary protein concentration was more than 50% lower than the baseline value, and urinary casts had decreased significantly. There were no significant changes in the levels of serum creatinine, serum anti-double-stranded DNA antibodies, or CH50 during any part of the study. The dose of glucocorticoids was significantly tapered by approximately 50%, without any disease flare. Hypertension developed in one patient, but was controlled with antihypertensive agents. Our results suggest that low-dose CsA therapy is an effective and less toxic alternative to conventional cyclophosphamide therapy for the management of refractory lupus nephritis.     

狼疮肾炎患者血清白细胞介素-18的升高与Th1/Th2型细胞的失衡

目的测定狼疮肾炎（LN）患者血清白细胞介素-18（IL-18）的水平以及外周血单个核细胞（PBMC）内干扰素（IFN）-γ／IL-4的表达情况，探讨LN患者体内Th1/Th2型细胞的平衡情况以及IL-18与Th1/Th2型免疫反应的相关性。方法酶联免疫吸附试验（ELISA）方法检测血清IL-18的表达：佛波酯（PMA）和离子霉素联合刺激培养，流式细胞术从单个核细胞水平检测细胞内IFN-γ/IL-4的表达情况。结果LN患者血清IL-18的水平显著高于对照组（P=0．000）；Th1型（IFN—γ^＋）细胞百分率明显高于对照组（P=0．009），Th1/Th2型细胞的比率（IFN-γ／IL-4^＋）明显增高（P=0．005）；Th1/Th2型细胞比率与尿蛋白定量（24h）呈明显正相关；Th1型细胞百分率与血清IL-18的水平呈明显的正相关。结论LN患者血清IL-18水平升高，并与Th1/Th2型免疫反应失衡有关，IL-18可以促进LN患者体内Th1型免疫反应增强。从而加重蛋白尿的发展。削弱Th1型免疫反应重建Th1/Th2型免疫反应的平衡，理论上可能会阻止狼疮肾炎的发病。     

Beneficial effects of melatonin in protecting against cyclosporine A-induced cardiotoxicity are receptor mediated

Melatonin, the chief product secreted by pineal gland, is capable of reducing free radical damage by acting directly as a free radical scavenger, and indirectly, by stimulating of antioxidant enzymes. Cyclosporine A (CsA) is the most widely used immunosuppressive drug, but its therapeutic use has several side effects including, i.e. nephrotoxicity and cardiotoxicity. This study was designed to examine the beneficial effects of melatonin in preventing CsA-induced cardiotoxicity. Additionally, we investigated the ability of melatonin to protect the rat heart via melatonin receptor. In one group of Wistar rats, melatonin (1 mg/kg/day i.p.) was administered concurrently with CsA (15 mg/kg/day s.c.) for 21 days. In another group of animals, melatonin was injected with CsA and luzindole, an antagonist of melatonin receptors. Oxidative stress in heart tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione levels and antioxidant enzyme activities including catalase and superoxide dismutase. CsA administration for 21 days produced elevated levels of TBARS, marked depletion of cardiac antioxidant enzymes and caused morphological alterations in myocardial fibers. Melatonin markedly reduced TBARS levels, increased the antioxidant enzyme levels and normalized altered cardiac morphology. The protective effects of melatonin were lost when the animals received the melatonin receptor antagonist. In conclusion our study shows that, (a) melatonin significantly reduces CsA cardiotoxicity, and (b) the reduction in CsA-induced cardiotoxicity was mediated by the binding of melatonin to its membrane receptors.     

Low dose cyclosporine A in the treatment of resistant proliferative lupus nephritis

Objective: This study aimed to evaluate long-term efficacy of low dose cyclosporine A (CsA) in the treatment of resistant proliferative lupus nephritis.

Methods: In this retrospective study, patients with biopsy proven proliferative lupus nephritis who were unresponsive to combination therapy with steroid plus mycophenolate mofetil (MMF) or cyclophosphamide (CYC) and had been treated with CsA were included. Efficacy monitoring was based on the systemic lupus erythematosus (SLE) disease activity index, dose of prednisolone, serum complement, anti–double stranded DNA (anti-dsDNA) titration, urine analysis, proteinuria, creatinine clearance, remission of the renal disease, renal survival and involvement of other organs.

Results: This study included 27 consecutive patients (22 females, 5 males) with resistant proliferative lupus nephritis. Mean duration of follow up and treatment with CsA were 40.7?±?24.9 and 35.2?±?19.1 months, respectively. Complete and partial renal remission occurred in 66.9% and 25.7% patients, respectively. Creatinine clearance was stable, proteinuria and anti-dsDNA titer decreased, and C3 and C4 increased significantly during the treatment with CsA. Severe complications such as death, dialysis, kidney transplantation and severe infection did not occur in the studied patients during the follow-up period.

Conclusions: Low-dose CsA could induce renal remission and ameliorate the SLE disease activity in patients with resistant proliferative lupus nephritis and it would be a safe drug for treatment of these patients.     

狼疮性肾炎患者白细胞介素-13的表达及其临床意义

目的 探讨狼疮性肾炎(LN)患者血浆及肾组织白细胞介素-13(IL-13)的表达及其临床意义。方法 采用ELISA法检测血浆IL-13水平，采用免疫组化ABC法检测肾组织IL-13的表达。结果 LN患者血浆IL-13水平、肾小球及肾小管间质区IL-13表达较对照组和非LN肾脏病对照组增高，以Ⅳ型LN患者肾小球区IL-13表达最高，而不同病理类型的LN肾小管间质区IL-13表达无显著性差异。LN患者血浆及肾小管间质区IL-13表达与Ccr和血清C3呈负相关，与肾小管间质病变活动指数和肾小球病变活动指数呈正相关。结论 IL-13参与LN的分子病理机制，血浆及肾组织IL-13水平可能有助于判断狼疮活动程度。     

Plasma soluble interleukin-2 receptor in patients with primary myelofibrosis

Summary Using an enzyme-linked immunosorbant assay (ELISA) test, the level of soluble Tac peptide, one chain of the human interleukin-2 receptor, was measured in the plasma of 26 patients with primary myelofibrosis (MF), seven patients with polycythaemia vera and 11 normal controls. The plasma soluble interleukin-2 receptor (sIL-2R) was found to be significantly elevated in patients with primary MF compared to polycythaemia vera or controls ( P <0·01), while the plasma sIL-2R of patients with polycythaemia vera also was found to be significantly elevated compared to controls ( P <0·01). The significantly elevated value of sIL-2R seen in primary MF may be secondary to T cell activation resulting from autoimmune phenomena, and myeloblast activation with release of sIL-2R may also be a contributing factor. In primary MF, plasma sIL-2R levels were also found to be correlated to survival, circulating blast cell counts, and thrombocytopenia, but not to white blood cell counts, LDH levels, degree of marrow fibrosis, or degree of splenomegaly. Patients with primary MF with higher titre of plasma sIL-2R had a shorter survival. Further studies involving more patients and longer follow-up may substantiate that plasma sIL-2R is an important prognostic indicator in primary MF.     

他巴唑和甲状腺素对Graves'病患者sIL-2R的影响

研究他巴唑和甲状腺素对Ｇｒａｖｅｓ’病患者ｓＩＬ－２Ｒ的影响。方法将２５例Ｇｒａｖｅｓ’病患者外周血单个细胞在不同浓度的他巴唑和甲状腺素条件下进行体外增减同时检测培养上清液及血浆ｓＩＬ－２Ｒ水平并与血浆游离Ｔ３（ＦＴ３）和游离Ｔ４（ＦＴ４）作相关分析。结果ＧＤ患者血浆ｓＩＬ－２Ｒ较正常对照明显升高,并与血浆ＦＴ３和ＦＴ４成正相关（分别为（Ｐ〈０．０５和Ｐ〈０．０１）;ＧＤ患者ＰＢＭＣ培养上清ＳＩＬ     

环孢素A体内抗日本血吸虫的实验研究

目的 观察环孢素A体内抗日本血吸虫的作用。方法 96只长爪沙鼠随机分8组,每组12只,A组为正常组,B组为模型组,C、D、E、F、G和H为治疗组。B、C、D、E、F、G和H组以腹部贴片法感染日本血吸虫尾蚴,每鼠感染120±2条尾蚴,于感染后(Day 0)和第3周(Day 21)对C、D、E、F、G和H各组分别给予3种不同剂量(10,20,50 mg/kg·d)的环孢素A治疗,连续5天。5周后解剖全部沙鼠,经门静脉灌注收集成虫,计数虫荷,计算减虫率。收集到的虫体重新分组,扫描电镜(SEM)和透射电镜(TEM)观察虫体表面损害情况。病理学观察:取沙鼠肝脏和肠壁制作常规病理切片,然后进行HE染色观察虫卵肉芽肿面积大小,Masson染色观察肝脏纤维化程度。结果 解剖结果显示,所有被感染沙鼠均有不同程度的虫卵结节产生,经环孢素A治疗后,各剂量组沙鼠肝脏虫卵结节均有减少,尤其高剂量组效果显著。HE染色结果显示,低剂量组肉芽肿面积与模型组相比没有明显改变,随着剂量的增加,肉芽肿面积减小,虫卵数量减少。高剂量组几乎未见虫卵。Masson染色同样显示随着剂量提高,纤维化程度逐渐减轻。应用扫描电镜可观察到未给药组雄、雌虫体体壁结果正常,凹窝、体棘和感觉乳突等清晰可见。用药后雄、雌虫体体壁表面破损严重,低剂量组可见表皮皱缩,凹凸不平;高剂量组虫体表皮溃烂,伴有大面积的脱落。透射电镜可见雌、雄虫体体壁产生大量空泡产生,体表细胞结构紊乱。结论 环孢素A在体内可使童虫和成虫受损或致死,呈剂量依赖性,具有明显的抗日本血吸虫作用。     

氯沙坦抑制环孢素A诱导的系膜细胞增生和细胞外基质形成

目的：观察免疫抑制剂环孢素A(CsA)对系膜细胞(MC)增生及细胞外基质(ECM)分泌的影响以及氯沙坦的干预作用，初步探讨环孢素致肾小球硬化的机制。方法：体外培养大鼠肾小球MC，用氚标胸腺密暖核苦(^3H-TdR)掺入法测定CsA对MC增生的影响，用酶联免疫吸附实验(ELISA)测定细胞上清液中转化生长因子β1(TGF—β1)及ECM成份纤维连接蛋白(fibronectin,Fn)的分泌，用逆转录-聚合酶链反应(RT—PCR)方法测定TGF—β1、I型前胶原、基质金属蛋白酶2(MMP—2)的基因表达。结果：CsA对MC的增生有明显的抑制作用，并呈现时间和剂量依赖效应，氯沙坦对细胞的增生无明显作用；环孢素能明显促进TGF—β1及Fn的分泌，并能促进TGF—β1、I型前胶原mRNA的表达，下调MMP—2 mRNA的表达，氯沙坦能下调环孢素诱导的TGF—β1及Fn的表达。结论：环孢素影响MC增生和ECM分泌从而引起肾小球硬化，肾素—血管紧张素—醛固酮系统可能部分参与了这一过程。