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1.
Leflunomide免疫抑制作用的实验研究   总被引:1,自引:0,他引:1  
为了寻找一种抗排斥、疗效好且毒性低的免疫抑制药物,应用Leflunomide(LFM,雷抑素)对大鼠移植模型进行研究,实验分为对照组、LFM组、CsA组和LFM+CsA组。结果显示LFM2.5mg.kg-1.d-1和CsA2.5mg.kg-1.d-1术后灌服7天,大鼠移植器官存活时间分别为18.2±1.5和13.5±1.3天,较对照组7.2±1.2天明显延长,LFM和CsA联合用药,移植物存活时间26.8±5.7天,较单纯用药效果更好。证明LFM具有显著的抗排斥作用,与CsA合用有协同作用;LFM在移植后4天给药,仍可逆转淋巴细胞在移植物内的浸润,能较快地逆转移植物的排斥反应。  相似文献   

2.
为探讨NIDDM患者Fn、PAG改变与缺血性心脑血管病的关系,分析53例NIDDM患者Fu、PAG测定结果,并与53名健康人比较。患者组Fn明显高于(P〈0.01),前者PAG(1)、MAR、I与后者有显著统计学差异(P〈0.01)。患者组中并发症组与无并发症组Fn、I较对照组有明显统计学差异(P〈0.01),并发症组PAG(1)、MAR明显高于对照组(P〈0.05)。NIDDM患者Fn降低、PA  相似文献   

3.
目的 探讨移植肠白细胞介素2 受体( I L2 R) 和细胞间粘附分子1( I C A M1) 的表达在小肠移植排斥反应中的意义及诊断价值。方法 选用近交系大鼠 F344/ N 和 Wistar/ A 进行全小肠异位移植,实验分4 组,第1 组: Wistar;第2 组: Wistar→ Wistar ;第3 组: F344 → Wistar;第4 组: F344 → Wistar+环孢霉素 A(6 mg·kg - 1·d - 1) 。术后第3 、5 、7 天取各组动物移植肠标本进行病理学检查,应用免疫组化技术( S P 法) 检测移植肠 I L2 R 和 I C A M1 的表达。结果 病理学检查显示第3 组大鼠在术后第3 、5 、7天分别符合轻、中、重度排斥,第2 、4 组无明显排斥征象。第3 组 I L2 R 表达在术后均非常显著高于其他3 个对照组;第3 组 I C A M1 表达在术后第3 、5 天较相似,尤其在上皮细胞表现为强阳性,并显著高于第1 组。但第2 、4 对照组 I C A M1 表达也较高,第3 组仅在术后第3 天 I C A M1 评分显著高于第2 组。结论  I L2 R 和 I C A M1 阳性细胞在小肠移植排斥反应过程中发挥重要作用。应用单克隆抗体阻  相似文献   

4.
为探讨融合蛋白(CTLA4Ig) 基因在糖尿病大鼠体内表达及其产物延长胰岛移植物存活的作用,利用脂质体(Lipofectin) 载体包裹CTLA4IgcDNA 质粒后转染鼠胰岛和肌肉细胞,检测移植后CTLA4Ig 基因表达水平和T 淋巴细胞转化率,观察CTLA4Ig 基因表达在延长糖尿病鼠胰岛移植物和大鼠存活时间的作用。结果: 胰岛移植术后实验( A) 组、对照(B) 组T 淋巴细胞转化率有明显差异( P< 0 .05) 。A 组胰岛移植后第7 天2 只大鼠血清CTLA4Ig 呈阳性( 阳性率为20 % ) ,分别为14 ng/ ml 和31 ng/ ml。B 组胰岛移植后维持血糖正常时间平均3 .6 ±5 .1 天,A 组胰岛移植后维持血糖正常时间平均14 .8 ±12 .3 天,两组比较差异有显著性意义( P< 0 .05 ) 。A 组大鼠平均存活24 .0 ±10 .8 天,最长45 天,B 组大鼠平均存活10 .8 ±4 .8 天,最长21 天,两组大鼠生存时间差异有统计学意义( P< 0 .01) 。本实验结果提示:CTLA4Ig 基因可以在受体大鼠胰岛细胞或肌肉组织表达,其表达产物可使胰岛移植物和受体鼠存活时间明显延长。  相似文献   

5.
观察64例梗阻性黄疸患者和39例单纯胆囊结石(C组)患者血流动力学变化及吲哚美辛的调节作用。梗阻性黄疸患者分为非吲哚美辛组(A组)和吲哚美辛组(B组)。结果表明A组每博量、心输出量和心脏指数显著高于C组(P<001),平均动脉压(MAP)、周围血管阻力(SVR)和门静脉血流速度(PVBF)显著低于C组(P<001)。B组术前MAP,SVR和PVBF显著高于A组(P<001),B组术后上述指标进一步改善,但与C组比较仍有显著差异(P<001)。本组结果显示,术前口服吲哚美辛有改善梗阻性黄疸患者循环功能、门脉血流和肝功能作用。  相似文献   

6.
我们通过对39例骨软化症,69例再生不良性骨病的尿毒症患者骨活检资料分析,证明这两种类型的共同组织学特征为破骨细胞数减少,骨矿化率(BMR)和骨生成率(BFR)降低,矿化时间(MLT)延长,故属低运输。两组比较,OM组的骨前质面积、长度和宽度均显著增加(P<0.01),MLT更为延长(P<0.05),而ABD组骨小梁面积显著减少(P<0.05)。OM和ABD组的骨铝阳性率分别为84.6%和64.2  相似文献   

7.
目的 寻找延长非协调性异种心脏移植存活时间的方法。方法 实验分A、B、C、D4组,将异种心脏(豚鼠-大鼠)移植于颈部。A组:移植前受体用眼镜蛇蛇毒因子(CVF)150ug.kg-1.d^-1,腹膜腔内注射(i.p),每天分2次,相隔3d,共4次;B组:在A组的基础上,移植前1h加用己酮可可碱(PTX)50mg/kg(i.p),然后每隔6h按25mg/kg(i.p)至发生排斥反应为止;C组:在A组的  相似文献   

8.
己酮可可碱、孕酮和A23187对人精子甘露糖受体表达的影响   总被引:7,自引:0,他引:7  
人精子经BWW获能5~6小时后,分别用己酮可可碱(PF)、孕酮(P)和A23187三种已知的获能及(或)顶体反应促进剂处理1小时,对实验和对照组精子用异硫氰酸荧光素标记的甘露糖化牛血清白蛋白(M FITC BSA)作探针标记精子甘露糖受体(MR)。结果表明,获能促进剂PF并不促进MR表达而P和A23187则有显著促进MR表达的作用。P对MRII型的促表达作用略强于对II型,而A23187则对II型的促进显著强于I型。认为MR的表达是一种依赖于钙离子的细胞生物学过程,并与顶体反应有密切关系。推测MR可能具有介导精子与卵膜融合的作用。  相似文献   

9.
左旋精氨酸在心脏外科围术期的应用   总被引:4,自引:1,他引:3  
目的:探讨心脏手术中自由基对心脏血管内皮细胞释放一氧化氮(NO)的影响及利用左旋精氨酸增强内皮细胞功能方面的价值。方法:40例体外循环下行心脏手术患者,20例为治疗组,在开始体外循环前由颈内静脉注射左旋精氨酸(L-arginine,L-Arg)100mg/kg。动态监测围术期血丙二醇(MDA)、总自由基(TFR)及超氧化物歧化酶(SOD)。结果:对照组MDA及TFR在不同时点变化均大于治疗组(P〉  相似文献   

10.
目的;为了探讨对扩张型心肌酶(DCM)无症状性心力衰竭(AHF)患者早期干预的临床研究,以延长住院间事时期提高患者生活、生存质量。方法:对32例前列素E1(PGE1)治疗组治疗前后血浆ET浓度进行比较。对64例DCMAHF患者观察与随访。结果:PGE1治疗左心室(LV)≥65mm和〈65mm心功能不全患者同样有铲。两者治疗前后比较均呈非常显著差异。PGE1治疗组与对照组比较,PGE1治疗组改善心功  相似文献   

11.
BACKGROUND: Chronic rejection is the leading cause of long-term allograft loss. Until now, no therapy has been recognized as being efficient in its prevention. In addition to their immunosuppressive activity, mycophenolate mofetil (MMF) and rapamycin (RAPA) show diverse properties against vascular smooth muscle cell activity, cell-adhesion molecule expression, and ischemia-reperfusion injury. The combination effect of MMF and RAPA was tested to prevent chronic renal allograft rejection in the rat in this study. METHODS: Nephrectomized Lewis recipients underwent orthotopic transplantation with Fisher (F344) kidneys (allograft groups) or Lewis kidneys (isograft control). The initial episode of acute rejection was controlled with a short course of cyclosporine A (CsA) (1.5 mg/kg/day for 10 days). From weeks 4 to 20, animals were thereafter treated every other day either with vehicle, MMF (20 mg/kg), RAPA (0.8 mg/kg), or MMF (20 mg/kg) plus RAPA (0.8 mg/kg) in combination. Animals were sequentially killed at serial intervals over a follow-up of 50 weeks, and histologic study was performed on harvested kidneys according to the Banff working classification for allograft pathology. RESULTS: Animals treated with MMF or RAPA alone showed a Banff sum score similar to the allograft control group (6.31+/-1.01 and 7.27+/-1.14 vs. 7.21+/-1.14, respectively; P>0.05). When the recipient rats were treated with MMF and RAPA in combination, it resulted in a clinically and statistically significant reduction of Banff sum score (4.21+/-0.79, P<0.01), with specific inhibition of vascular fibrous intimal thickening, allograft glomerulopathy, and interstitial fibrosis. CONCLUSION: Over a 50-week study, concomitant therapy of MMF and RAPA prevents chronic renal allograft rejection, probably through reduction of ischemic and cytotoxic degenerative changes. These results warrant further investigation in the combination of MMF and RAPA as anti-chronic rejection therapy in clinical transplantation.  相似文献   

12.
BACKGROUND: The effects of tacrolimus (FK506) and malononitrilamides (MNA) (FK778 and FK779) monotherapy and combination therapy were examined in prevention of acute heart and kidney allograft rejection and reversal of ongoing acute heart allograft rejection in the rat. METHODS: Brown Norway (RT1n)-to-Lewis (RT11) and ACI (RT1a)-to-Lewis (RT11) combinations were used, respectively, for heart and kidney transplantation models. Immunosuppressants were administered orally from day 1 to day 14 for preventing acute rejection and from day 4 to day 34 after transplantation for the reversal of ongoing acute rejection. RESULTS: In the prevention of acute heart rejection model, recipient rats treated with monotherapy of tacrolimus or MNA (FK778, FK779) showed a dose-related prolongation of mean survival time (MST) compared with naive control rats (P<0.01). The mean survival time in combination therapy of tacrolimus (FK506) and FK778 indicated that an additive to synergistic interaction was produced when compared with the respective monotherapies (combination index [CI]=0.631-1.022). These results were reproducible with tacrolimus and FK779 combination therapy (CI=0.572-0.846). Furthermore, similar results were also found in the prevention of acute kidney allograft rejection in the rat (CI=0.137-0.516). In the reversal of ongoing acute heart allograft rejection, combination therapy of tacrolimus and FK778 demonstrated a strong synergistic interaction (CI=0.166-0.970) compared with monotherapy of tacrolimus or FK778. CONCLUSIONS: Combination therapy of tacrolimus and MNA (FK778, FK779) produces synergistic effects in prevention of acute heart and kidney rejection and reversal of ongoing heart allograft rejection in the rat.  相似文献   

13.
Jiang W  Jiang J  Xu D  Wang X  Qi S  Ouyang J  Ma A  Vu MD  Bilolo KK  Chen H 《Microsurgery》2003,23(2):117-122
The application of multiple immunosuppressive therapy for organ transplantation could enhance therapeutic efficacy, while minimizing the toxicity of individual drugs used in the regimen. In this study, the effect of the combined therapy of vincristine (VCR) with tacrolimus (FK506) or sirolimus (rapamycin, RAPA) was tested in prevention of acute heart allograft rejection in the rat. A Brown Norway (BN, RT 1(n)) to Lewis (LEW, RT 1(1)) rat combination was used in a heart allografting model. VCR was administered intraperitoneally once daily, while FK506 and RAPA were given by gavage once daily for 14 days after transplantation. There were dose-related prolongations of mean survival time (MST) to monotherapy of VCR, FK506, or RAPA. The MST in combination therapy indicated that a synergistic interaction was produced when compared with the respective monotherapies: VCR 0.05 mg/kg/day + FK506 0.5 mg/kg/day (16.00 +/- 1.79 days, P = 0.001; combination index (CI) = 0.557); VCR 0.05 mg/kg/day + FK506 1.0 mg/kg/day (29.00 +/- 10.54 days, P = 0.001; CI = 0.598); VCR 0.05 mg/kg/day + RAPA 0.2 mg/kg/day (17.33 +/- 1.97 days, P = 0.001; CI = 0.500); and VCR 0.05 mg/kg/day + RAPA 0.4 mg/kg/day (21.17 +/- 3.19 days, P = 0.001; CI = 0.838). Combination therapy of VCR and FK506 or RAPA produced synergistic effects in prevention of acute heart allograft rejection in the rat.  相似文献   

14.
目的 评价他克莫司(FK506)与FK778或FK779联合应用预防大鼠心脏移植排斥反应的效果。方法 大鼠异位心脏移植后单独应用FK506、FK778和FK779进行免疫抑制治疗,并设联合用药组。结果 单独用药组与不用药对照组相比,移植心脏存活时间明显延长,FK779组尤其显著;联合用药组移植心脏存活时间不但比对照组明显延长,而且明显长于各药同剂量单用组,FK506与FK779合用组尤其显著。结论 FK506、FK778和FK779均有很强的免疫抑制效应,FK506与FK778或FK779联合应用具有较强的协同效应。  相似文献   

15.
Sirolimus rescue therapy for refractory rejection in renal transplantation.   总被引:8,自引:0,他引:8  
J C Hong  B D Kahan 《Transplantation》2001,71(11):1579-1584
BACKGROUND: Acute renal allograft rejection episodes refractory to antilymphocyte preparations almost inevitably progress to transplantation loss. To reverse ongoing rejection processes, we administered sirolimus (RAPA) after failure of conventional immunosuppressive regimens including full courses of antilymphocyte sera. METHODS: All 36 renal transplantation recipients reported herein displayed either Grade IIB or Grade III biopsy-proven (Banff 1993 criteria) ongoing rejection episodes despite prior treatment with pulse and/or oral recycling of steroids and at least one 14- to 21-day course of murine (OKT3) or equine (ATGAM) antilymphocyte treatment. We compared the actual 12-month outcomes of two demographically similar cohorts of patients treated for refractory rejection with RAPA (Group I; n=24) or mycophenolate mofetil (MMF; Group II; n=12) added to a baseline regimen of cyclosporine (CsA)/prednisone (Pred). RESULTS: Rescue therapy reversed the renal dysfunction in 96% of patients in the RAPA group versus 67% in the MMF group (P=0.03) despite the fact that a greater fraction of patients in the RAPA (17 of 24) than the MMF group (6 of 12) had experienced two or more episodes of acute rejection before study entry and the fact that the recurrent bouts of acute rejection occurred within the first 6 months posttransplant in 94% of patients in the RAPA group compared with 50% (P=0.005) in the MMF group. Among the patients who were reversed successfully, the rates of rebound acute rejection were similar (4% vs. 8%). The mean serum creatinine values were slightly, although not significantly, lower among RAPA than MMF patients at 1, 3, 6, and 12 months: namely, 2.6 vs. 2.8, 2.8 vs. 3.2, 3.0 vs. 3.3, and 2.8 vs. 3.2 mg/dL, respectively. The 1-year patient and graft survival rates were similar: namely, 88% vs. 92% and 83% vs. 67% for the RAPA versus MMF groups. CONCLUSION: RAPA is a potent immunosuppressive agent for the treatment of refractory renal allograft rejection.  相似文献   

16.
BACKGROUND: Recent experimental data have shown that coadministration of microemulsion cyclosporine and the novel immunosuppressant SDZ-RAD potentiates the immunosuppressive efficacies of both drugs to suppress allograft rejection. Our study was designed to assess the potential of delayed SDZ-RAD administration, in addition to cyclosporine maintenance therapy, to reverse acute rejection in an allogeneic rat lung transplant model. METHODS: Unilateral left lung transplantation was performed using Brown-Norway donors implanted into Lewis recipients. An untreated control group and a cyclosporine monotherapy group (7.5 mg/kg) were followed for 7 days. An additional cyclosporine monotherapy group (7.5 mg/kg), and a combined therapy group treated with cyclosporine (7.5 mg/kg) plus SDZ-RAD (2.5 mg/kg), were followed for 21 days. For treatment of ongoing rejection, 7.5 mg/kg cyclosporine was given as maintenance therapy, and SDZ-RAD (2.5 mg/kg) was added on postoperative day 7. Drugs were given orally, and in the combined therapy regimens, administered 6 hours apart. Outcome variables included daily weight, radiographs, and histology. RESULTS: Radiographs on postoperative day 7 showed mild and moderate opacification of the left chest in the cyclosporine monotherapy groups and the untreated control group. Addition of SDZ-RAD to cyclosporine treatment on postoperative day 7 reversed opacification by postoperative days 14 and 21. Monotherapy with microemulsion CsA resulted in mild histological rejection by day 7, which progressed to moderate rejection by day 21. Addition of SDZ-RAD on postoperative day 7 reversed acute rejection, resulting in none or minimal rejection at day 21. CONCLUSIONS: SDZ RAD reverses acute rejection under cyclosporine maintenance therapy in a stringent lung allotransplant model.  相似文献   

17.
Cyclosporine (CsA) has substantially improved patient and graft survival rates in solid organ transplantation. In clinical studies, sirolimus has been shown to be as effective as CsA to maintain survival of renal and cardiac allografts without causing nephrotoxicity. Herein we describe a patient with biopsy-proven CsA-associated nephrotoxicity and refractory renal allograft rejection who was converted from steroids, CsA, and azathioprine to steroids, sirolimus (RAPA), and low-dose mycophenolate mofetil (MMF). The follow-up period was 60 months. We observed substantial improvement, even normalization in renal function. Our patient did not give consent to repeat biopsy after conversion. We also observed a beneficial effect of CsA withdrawal on blood pressure control. The spectrum of adverse events induced by sirolimus seemed to be mild relative to the potency of the immunosuppressive effect. The excellent response to combined RAPA and MMF in this patient was probably due to "concerted actions" of these agents on both B- and T-cell functions. The combination enhanced therapeutic efficacy while minimizing the toxicity of individual drugs used in the regimen. These findings suggest that sirolimus, when used as a base therapy in combination with low-dose MMF in a renal allograft recipient, may be an alternative to CsA-based therapy, providing potent immunosuppression of a renal allograft. Sirolimus administration facilitated steroids dose reduction.  相似文献   

18.
Despite novel immunosuppressive (IS) protocols, adverse effects of IS drugs continue to have notable negative impact on patient and cardiac allograft survival after heart transplantation (HTx). Therefore, IS regimens with less toxic side effects are sorely needed. We aimed to evaluate the efficacy of extracorporeal photopheresis (ECP) in combination with tacrolimus-based maintenance IS therapy in the treatment of allograft rejection in adult HTx recipients. Indications for ECP included acute moderate-to-severe or persistent mild cellular rejection, or mixed rejection. Twenty-two patients underwent a median of 22(2–44) ECP treatments after HTx. Median duration of ECP course was 173.5(2–466) days. No relevant adverse effects of ECP were noted. Reduction of methylprednisolone doses was safe throughout the ECP course. ECP, used in conjunction with pharmacological anti-rejection therapy, had a successful reversal of cardiac allograft rejection, decreased the rates of subsequential rejection episodes and normalized the allograft function in patients completing the ECP course. Short- and long-term survivals were excellent (91% at 1 and 5 years post-ECP) and comparable to International Society for Heart and Lung Transplantation registry data on HTx recipient overall survival. In conclusion, ECP can be safely used for the treatment and prevention of cardiac allograft rejection in conjunction with traditional IS regimen.  相似文献   

19.
Li Y  Li N  Wu B  Li J 《中华外科杂志》1999,37(6):372-374,I022
目的 明确移植肠上皮细胞凋亡在小肠移植排斥反应中的意义及诊断价值。方法 选用近交系大鼠F344/N和Wistar/A进行全小肠异位移植,实验分4组。第1组:非基本对照 ;第2组;同基因移植组;第3组;异基因移植组;第4组;异基因移植加环孢霉素A治疗组。术的第3、5、7天取移植肠进行病理学检查,采用TdT介导的脱氧核苷酸原位末端标记法(TUNEL)检测移植肠上皮细胞凋亡。结果 病理学检查显示第3组大  相似文献   

20.
目的 观察达利珠单抗联合环孢素A、霉酚酸酯和糖皮质激素预防肾移植后急性排斥反应的有效性和安全性。方法 由15家肾移植中心参加的开放性临床试验,共纳入72例首次尸肾移植受者为研究对象,在接受环孢素A、霉酚酸酯和糖皮质激素联合应用预防肾移植后急性排斥反应的同时,给予2剂人源化达利珠单抗,首剂给予时间为术前24h内,第2剂在术后第14d给予。对入选患者密切随访,评价肾移植后3个月和6个月时急性排斥反应的发生率、严重程度以及人、肾存活率;评价该治疗方法的安全性。结果 术后3个月内有3例患者发生4次急性排斥反应,3个月及6个月的排斥反应发生率均为5.56%;人/肾6个月和1年的存活率分别为95.8%/95.8%和94.5%/94.5%;仅有1例的腹痛可能与达利珠单抗有关。结论 2剂达利珠单抗联合环孢素A、霉酚酸酯和糖皮质激素预防肾移植后的急性排斥反应安全有效。  相似文献   

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