Tumor necrosis factor-related apoptosis-inducing ligand is a marker of kidney function and inflammation in heart and kidney transplant recipients

Background

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was originally identified as the third member of the TNF superfamily to induce apoptosis. TRAIL is normally expressed in many human tissues including kidney. Circulating soluble TRAIL is a negative marker for inflammation and is inversely associated with the mortality risk in chronic kidney disease patients. One increasingly prevalent complication in heart transplant recipients appears to be chronic kidney disease.

Materials and Methods

The aim of the study was to assess TRAIL concentration in 136 heart transplant recipients and 80 prevalent kidney allograft recipients in relation to kidney function. Complete blood count, urea, serum lipids, fasting glucose, creatinine, NT-proBNP were studied. Soluble TRAIL, hsCR P, interleukin-6 (IL-6), von willebrand factor (vWF) were assayed using commercially available kits.

Results

Heart transplant recipients had significantly higher serum creatinine, urea, cholesterol, triglycerides, fasting glucose, white blood cell count, serum TRAIL and lower estimated glomerular filtration rate than the control group. Similar results were obtained for kidney allograft recipients. Serum TRAIL levels fell, together with decline in glomerular filtration rate in heart transplant patients. Serum TRAIL was related to age, kidney function, erythrocyte count, hemoglobin, NT-proBNP, New York Heart Association class, presence of diabetes, high-density lipoprotein (HDL), IL-6, and ejection fraction. Age and HDL turn out to be predictors of TRAIL in heart transplant recipients. In kidney transplant recipients, TRAIL was related, in univariate analysis, to age, NT-proBNP, time after transplantation, kidney function, and vWF. In multiple regression analysis, predictors of TRAIL were vWF and time after transplantation.

Conclusion

TRAIL may represent a surrogate marker of endothelial dysfunction and atherosclerosis as these processes are accelerated in heart and kidney dysfunction.     

肿瘤坏死因子相关的凋亡诱导配体基因在糖尿病大鼠肾脏细胞凋亡中的作用

目的 探讨肿瘤坏死因子(TNF)相关的凋亡诱导配体(TRAIL)基因在糖尿病大鼠肾脏细胞凋亡中的表达及其作用。方法 应用链脲佐菌素建立糖尿病大鼠模型，采用原位末端标记法和流式细胞术检测4组(对照组、糖尿病4周组、8周组和12周组)大鼠肾脏细胞凋亡情况；免疫组化和流式细胞术检测肾脏TRAIL基因及其死亡受体DR4、DR5的蛋白表达。结果 与正常对照组相比．各糖尿病组较对照组肾小球、肾小管凋亡细胞数明显增多，TRAIL、DR4、DR5的表达亦显著增强。结论 在高糖环境的诱导下．TRAIL基因及其死亡受体出现的高表达，可能部分参与了糖尿病大鼠肾脏细胞凋亡。     

白细胞介素12通过抑制survivin表达加强肿瘤坏死因子相关凋亡诱导配体诱导的肝癌细胞凋亡

目的 探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)对肝细胞癌(HCC)的治疗作用,以及TRAIL耐药的可能机制和逆转耐药方案。方法 采用原位杂交方法观察HCC与正常肝组织中TRAIL的表达差异。采用不同浓度的sTRAIL(可溶性)处理HCC细胞株及真核表达质粒pIRES-EGFP-sTRAIL转染HCC细胞株,观察sTRAIL的抑癌疗效。建立裸鼠肝癌模型,观察sTRAIL的体内抑癌作用。进一步,检测HCC中survivin的表达并采用反义寡核苷酸封闭治疗。最后,观测sTRAIL和IL-12联合抗癌效果。结果 肝癌组织DR表达量显著强于正常肝组织DR表达量。60例肝癌组织中54例不表达诱捕受体DcRl,25例不表达DcR2,而20例正常肝组织均表达DcR。两种．HCC细胞株中DcR1表达缺失。经sTRAIL(100ng/ml)处理24h,HCC细胞凋亡发生率约10％,而Jurkat细胞凋亡率达70％以上。体外pIRES-EGFP-sTRAIL转染对肝癌细胞杀伤作用不敏感。体内直接瘤体注射pIRES-EGFP-sTRAIL可对裸鼠肝癌无明显抑制作用。HCC高表达survivin,反义寡核苷酸封闭可部分逆转TRAIL耐药。IL-12使survivin表达明显下调,显著加强TRAIL对HCC细胞的杀伤作用。结论 HCC对TRAIL诱导的凋亡有耐药现象。survivin参与HCC对TRAIL的耐药机制,反义寡核苷酸封闭可部分逆转TRAIL耐药。IL-12可通过抑制siurvivin表达增强TRAIL对HCC杀癌作用。联合基因治疗(如TRAIL和IL-12基因)可能成为一种有前途HCC治疗方案。     

移植物浸润T淋巴细胞肿瘤坏死因子相关凋亡诱导配体及受体DR4和DR5表达与大鼠小肠移植急性排斥反应的相关性

目的 探讨浸润T淋巴细胞七的DR4、DR5表达同小肠移植急性排斥反应的关系.方法 将2种近交系大鼠(SD、Wistar)54只按随机配对法分为A、B、C3组.A组大鼠为对照组(18只)行虚拟手术;B组(18只)大鼠行同系小肠移植;C组(18只)大鼠行不同品系小肠移植.各组大鼠于术后5 d取移植肠样本分别做HE染色和免疫荧光双标记染色.采用免疫荧光染色、激光共聚焦技术测定各组标本浸润T淋巴细胞肿瘤坏死因相关凋亡诱导配体及DR4、DR5的表达情况.结果 A组大鼠小肠黏膜正常,B组大鼠小肠表现为免疫耐受,C组大鼠表现为急性排斥反应.C组大鼠高T淋巴细胞表达肿瘤坏死因子相关凋亡诱导配体与A、B组大鼠比较差异有统计学意义(P < 0.01);A、B组大鼠浸润T淋巴细胞DR4、DR5均呈高表达,C组大鼠呈低表达,C组大鼠与A、B组比较差异有统计学意义(P < 0.01);A、B组大鼠比较差异无统计学意义(P > 0.05).结论 急性排斥反应的发生可能与浸润T淋巴细胞DR的低表达有关.减少浸润淋巴细胞DR表达的下调,或者上调DR将有助于控制急性排斥反应,诱导免疫耐受.     

移植物浸润T淋巴细胞肿瘤坏死因子相关凋亡诱导配体及受体DR4和DR5表达与大鼠小肠移植急性排斥反应的相关性

目的 探讨浸润T淋巴细胞七的DR4、DR5表达同小肠移植急性排斥反应的关系.方法 将2种近交系大鼠(SD、Wistar)54只按随机配对法分为A、B、C3组.A组大鼠为对照组(18只)行虚拟手术;B组(18只)大鼠行同系小肠移植;C组(18只)大鼠行不同品系小肠移植.各组大鼠于术后5 d取移植肠样本分别做HE染色和免疫荧光双标记染色.采用免疫荧光染色、激光共聚焦技术测定各组标本浸润T淋巴细胞肿瘤坏死因相关凋亡诱导配体及DR4、DR5的表达情况.结果 A组大鼠小肠黏膜正常,B组大鼠小肠表现为免疫耐受,C组大鼠表现为急性排斥反应.C组大鼠高T淋巴细胞表达肿瘤坏死因子相关凋亡诱导配体与A、B组大鼠比较差异有统计学意义(P < 0.01);A、B组大鼠浸润T淋巴细胞DR4、DR5均呈高表达,C组大鼠呈低表达,C组大鼠与A、B组比较差异有统计学意义(P < 0.01);A、B组大鼠比较差异无统计学意义(P > 0.05).结论 急性排斥反应的发生可能与浸润T淋巴细胞DR的低表达有关.减少浸润淋巴细胞DR表达的下调,或者上调DR将有助于控制急性排斥反应,诱导免疫耐受.     

移植物浸润T淋巴细胞肿瘤坏死因子相关凋亡诱导配体及受体DR4和DR5表达与大鼠小肠移植急性排斥反应的相关性

目的 探讨浸润T淋巴细胞七的DR4、DR5表达同小肠移植急性排斥反应的关系.方法 将2种近交系大鼠(SD、Wistar)54只按随机配对法分为A、B、C3组.A组大鼠为对照组(18只)行虚拟手术;B组(18只)大鼠行同系小肠移植;C组(18只)大鼠行不同品系小肠移植.各组大鼠于术后5 d取移植肠样本分别做HE染色和免疫荧光双标记染色.采用免疫荧光染色、激光共聚焦技术测定各组标本浸润T淋巴细胞肿瘤坏死因相关凋亡诱导配体及DR4、DR5的表达情况.结果 A组大鼠小肠黏膜正常,B组大鼠小肠表现为免疫耐受,C组大鼠表现为急性排斥反应.C组大鼠高T淋巴细胞表达肿瘤坏死因子相关凋亡诱导配体与A、B组大鼠比较差异有统计学意义(P < 0.01);A、B组大鼠浸润T淋巴细胞DR4、DR5均呈高表达,C组大鼠呈低表达,C组大鼠与A、B组比较差异有统计学意义(P < 0.01);A、B组大鼠比较差异无统计学意义(P > 0.05).结论 急性排斥反应的发生可能与浸润T淋巴细胞DR的低表达有关.减少浸润淋巴细胞DR表达的下调,或者上调DR将有助于控制急性排斥反应,诱导免疫耐受.     

肿瘤坏死因子相关的凋亡诱导配体系统和核因子κB在糖尿病大鼠肾脏中的表达

目的探讨肿瘤坏死因子相关的凋亡诱导配体（TRAIL）系统在糖尿病肾病发生发展中的作用。方法观察TRAIL及其死亡受体4（DR4）、诱骗受体2（DcR2）和核因子KB（NF-KB）在糖尿病大鼠不同时期肾脏中的表达及分析其与肾功能的关系。将80只Wistar大鼠随机分为对照组（NC组）和糖尿病组（DM组），一侧肾切除后，腹腔注射链脲佐菌素（STZ，55mg／kg）建立糖尿病大鼠模型。在第4、8、12、16周末，随机处死各组8只大鼠，收集血液、尿液和肾组织，检测血生化指标、尿蛋白量（24h）和肥大指数等。应用荧光实时定量RT-PCR和免疫组织化学的方法检测肾皮质TRAIL及其受体DR4、DcR2和NF-KB的mRNA和蛋白的表达情况。结果各时间点DM组大鼠尿蛋白量（24h）和肥大指数（肾质量，体质量）均显著高于NC组（P〈0．05）；血白蛋白在第8周末开始显著低于NC组（P〈0．01）；Scr、BUN于第16周末显著高于NC组（P〈0．01）。DM组大鼠TRAIL及其受体DR4mRNA在第4、8及12周末时表达均显著低于NC组（P〈0．01）；第16周末时表达显著高于NC组（P〈0．01）。DM组大鼠DcR2mRNA在第4、8及12周末时表达均显著高于NC组（P〈0．01）；NF-KB的基因表达均显著高于NC组（P〈0．05）。免疫组化结果显示TRAIL及其受体DR4、DcR2主要在肾小管表达，而在肾小球和脉管系统未见表达；NF-KB在肾小球和肾小管均有表达；TRAIL及其受体和NF-KB在各组表达趋势与PCR结果一致。结论TRAIL系统作为调节细胞凋亡的一组重要因子，参与了糖尿病肾病的发生发展。     

Relationship between serum levels of tumour necrosis factor-related apoptosis-inducing ligand and the survival of Chinese peritoneal dialysis patients

Aim: Tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) can counteract inflammation and atherosclerosis, both common causes of morbidity in peritoneal dialysis (PD) patients. We examined the relation between serum soluble TRAIL (sTRAIL) levels and the outcome of Chinese PD patients. Methods: We studied 116 new PD patients (67 males, age 56.7 ± 13.4 years). Baseline serum sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest). All patients were followed for 20.9 ± 7.0 months. Results: Patient survival was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months (P = 0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was an independent predictor of patient survival after adjusting for confounding factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935–0.991, P = 0.010). Conclusion: A higher baseline serum sTRAIL level was associated with a better survival of PD patients. The detailed mechanism deserves further investigation.     

The extent of HLA‐DR expression on HLA‐DR+ Tregs allows the identification of patients with clinically relevant borderline rejection

Regulatory T cells (Tregs) were shown to be involved into the pathogenesis of acute rejection after transplantation. The suppressive activity of the total regulatory T cell pool depends on its percentage of highly suppressive HLA‐DR⁺‐Treg cells. Therefore, both the suppressive activity of the total Treg pool and the extent of HLA‐DR expression of HLA‐DR⁺‐Tregs (MFI HLA‐DR) were estimated in non transplanted volunteers, patients with end‐stage renal failure (ESRF), healthy renal transplant patients with suspicion on rejection, due to sole histological Bord‐R or sole acute renal failure (ARF), and patients with clinically relevant borderline rejection (Bord‐R and ARF). Compared to patients with only Bord‐R or only ARF, the suppressive activity of the total Treg cell pool was exclusively reduced in patients with clinically relevant Bord‐R. In parallel, the HLA‐DR MFI of the DR⁺‐Treg subset was significantly decreased in these patients, due to a significantly lower proportion of DR^high+‐Tregs, which were shown to have the highest suppressive capacity within the total Treg pool. Our findings clearly demonstrate that the determination of the HLA‐DR MFI of the HLA‐DR⁺‐Treg subset allows a highly sensitive, specific and non‐invasive discrimination between patients with clinically relevant Bord‐R (Bord and ARF) and patients with subclinical rejection or other causes of transplant failure.     

Sensitivity of prostate cells to TRAIL-induced apoptosis increases with tumor progression: DR5 and caspase 8 are key players

BACKGROUND: As advanced prostate cancers are resistant to currently available chemotherapies, we evaluated the cytotoxic effect of TNF-related apoptosis-inducing ligand (TRAIL) and characterized the involvement of its five receptors DR4, DR5, DcR1, DcR2, and osteoprotegerin (OPG) and of the death-inducing signaling complex (DISC)-forming proteins caspase 8 and c-FLIP in prostate cell lines. METHODS: We used six prostate cell lines, each corresponding to a particular stage in prostate tumorigenesis, and analyzed TRAIL sensitivity in relation to TRAIL receptors' expression. RESULTS: TRAIL sensitivity was correlated with tumor progression and DR5 expression levels and apoptosis was exclusively mediated by DR5. DcR2 was significantly more abundant in tumor cells than in non-neoplastic ones and may contribute to partial resistance to TRAIL in some prostate tumor cells. Conversely, non-tumoral cells secreted high levels of OPG, which can protect them from apoptosis. Finally, caspase 8 expression levels were as DR5 directly correlated to TRAIL sensitivity in prostate tumor cells. CONCLUSION: TRAIL-induced apoptosis is closely related to the balanced expression of its different receptors in prostate cancer cells and their modulation could be of potential clinical value for advanced tumor treatment.     

Expression of TRAIL and death receptor DR4 in Palmer type 2 TFCC lesions

Introduction

Degenerative articular disc perforations of the triangular fibrocartilage (TFC) of the wrist are characterized by fibrocartilage cell loss and are often associated with ulna-plus situations. Apoptosis has been found to play a crucial role in fibrocartilage cell loss, however, the molecular mechanism and mediators are still poorly understood.

Aim

The purpose of this study was to identify receptors to apoptosis in degenerative disc lesions.

Patients

Included in the study were 17 patients with degenerative articular disc tears of the TFC (Palmer type 2C). Following arthroscopic debridement of the TFC, histological sections were examined to assess the presence of apoptosis. Apoptosis was determined using TRAIL and death receptor DR4 agonists for immunohistochemical analyses. The number of cells positive for apoptosis was then correlated with ulna length.

Results

Cells positive for TRAIL and DR4 were found in all specimens. The number of cells positive for TRAIL was significantly increased in specimens of patients with an ulna positive variance (P = 0.040). However, DR4 was not significantly increased in ulna plus (P > 0.05). Both, TRAIL and DR4 positive cells were found to be evenly distributed throughout each specimen. There was no accumulation of any type of cells in any particular zone of the biopsies.

Conclusion

This is the first study that shows that TFCC cells express TRAIL and DR4, which suggests that apoptosis, as well as, mechanical trauma are involved in the development of disc perforation. The TRAIL/DR4 receptor system is a molecular mediator of apoptosis induction in TFC cells and therefore plays a role in cell loss in degenerative disc lesions.     

肿瘤坏死因子相关凋亡诱导配体受体在肾癌中的分布及其意义

目的：研究肿瘤坏死因子相关诱导凋亡配体（TRAIL）受体在肾癌组织中的分布及其意义。方法：采用RT－PCR及NorthernBlot的方法检测TRAIL受体在肾癌组织及正常肾组织,肾癌细胞系GRC－I和正常肾小管细胞系HK－2中的表达。结果：死亡受体DR4、DT4在肾癌组织及正常肾组织、肾癌细胞系GRC－I和正常肾小管细胞系HK－2中强表达;假受体DcR-1在正常肾组织和正常肾小管细胞系HK－2中强表达;假受体DcR-2未见表达。结论TRAIL基因在肾癌肿瘤细胞的凋亡机制中可能发挥重要的作用。     

肾移植受者血清可溶性HLA—Ⅰ类抗原的动态监测

目的 了解血清可溶性ＨＬＡ－Ⅰ类抗原（ｓＨＬＡ－Ⅰ）与肾移植受发生急性排斥反应及感染的关系。方法 应用酶联免疫法动态监测３６例肾移植受ｓＨＬＡ－Ⅰ水平。结果尿毒症组ｓＨＬＡ－Ⅰ水平为（２．９４±０．３４）μｇ／Ｌ,显高于正常对照组（０．７６±０．３３）μｇ／Ｌ（Ｐ〈０．０５）。移植后功能稳定组ｓＨＬＡ降至（０．６３±０．３１）μｇ／Ｌ,显低于尿毒症组（Ｐ〈０．０５）。ｓＨＬＡ－Ⅰ在发生排斥     

Relationships Between HLA‐A, ‐B, ‐DQ and ‐DR Antigens and Interstitial Fibrosis in Renal Allografts

Although renal transplant recipients tend to exhibit similar clinical and immunological changes over time, some allograft biopsies show early IF. To evaluate the relationship between HLA antigens and IF in renal allografts, we reviewed for HLA‐A, ‐B, ‐DQ, and ‐DR antigens in 88 renal transplant recipients. For each antigen type, we determined the numbers of patients who did and did not possess the antigen. We then determined the mean time to onset of IF for each of these two groups, and statistically compared the means. In the second part of the analysis, we divided the 88 patients into those who did and did not show IF at 6 months posttransplantation, and then calculated the prevalence of each antigen type in the IF (+) and IF (?) groups. This same procedure was repeated with the patients grouped according to presence of IF at 12 months posttransplantation. The patient groups with HLA‐B8, ‐B27, ‐DQ2, ‐DQ5, ‐DQ6, ‐DQ7, ‐DR4, ‐DR13, and ‐DR15, respectively, had significantly shorter times to IF onset after transplantation than the corresponding groups without these antigens (p < 0.05). The groups that were IF (+) at 6 and 12 months posttransplantation had significantly higher frequencies of HLA‐B8, ‐B27, ‐DQ2, and ‐DR4 than the corresponding IF (?) groups at these two time points (p < 0.05). The results indicated that any kidney recipient with these antigens is predisposed to developing diffuse IF in their graft relatively soon after transplantation. We conclude that although there are multiple etiological agents in the pathogenesis of interstitial fibrosis, one cannot exclude an HLA association in these cases.     

Sensitization of human renal cell carcinoma cell lines to TRAIL-induced apoptosis by anthracyclines

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new member of the tumor necrosis factor family. The present study investigated whether anthracyclines enhance TRAIL-induced apoptosis and cytotoxicity in renal cell carcinoma (RCC) cells. METHODS: Cytotoxicity was measured using the microtiter assay. Apoptosis was monitored using DNA ladder analysis. Caspase activity was determined using a quantitative colorimetric assay. RESULTS: Treatment of ACHN and Caki-1 human RCC lines with TRAIL, in combination with subtoxic concentrations of epirubicin (EPI) or pirarubicin (THP), enhanced induction of apoptosis and cytotoxicity. Sequential treatment with EPI followed by TRAIL induced significantly more cytotoxicity than the inverse treatment. The combined cytotoxicity of TRAIL and EPI was significantly inhibited by the TRAIL-neutralizing fusion protein DR5:Fc, although EPI did not affect the mRNA expression of DR4, DR5, DcR1 or DcR2. The combination treatment with TRAIL and EPI activated caspase-6 and -3, which were downstream molecules of the death receptor. Furthermore, the combined cytotoxicity of TRAIL and EPI was almost completely inhibited by Z-VAD-FMK, and partly inhibited by Ac-DMQD-CHO. CONCLUSION: These findings indicate that anthracyclines sensitize RCC cells to TRAIL-induced apoptosis and cytotoxicity through activation of caspases, suggesting that TRAIL, in combination with anthracyclines, has a therapeutic potential in the treatment of RCC.     

Involvement of platelet-derived growth factor and histocompatibility of DRB 1 in chronic renal allograft nephropathy

BACKGROUND: The role of activated T cells in graft arteriosclerosis, which is observed in chronic renal allograft nephropathy, and the involvement of major histocompatibility complex (MHC) incompatibility remain to be determined. We examined the effect of T lymphocytes that were obtained from renal transplant patients undergoing chronic rejection treated with cyclosporine (CsA) on platelet-derived growth factor (PDGF)-induced proliferation of cultured human vascular smooth muscle cells (SMC) and compared the proliferation activity of T lymphocytes with MHC incompatibility, especially DRB 1 mismatch. METHODS: Renal transplant patients with continued allograft function, who survived more than 1 year after transplantation, were recruited. Chronic rejection was documented by graft-biopsy findings together with increasing serum creatinine levels (10-20% per year). After the incubation of supernatant (conditioning medium) of cultured T cells from CsA-treated renal transplant patients with chronic rejection (n=18) and with normal renal function (n=14) as control, normal subjects (n=11) and chronic hemodialysis (HD) patients (n=5) with cultured SMC in the presence or absence of PDGF, DNA synthesis (3H-thymidine uptake) of SMC was examined. The in vitro effects of CsA on DNA synthesis of cultured SMC were also evaluated. RESULTS: The supernatant of cultured T cells from renal transplant patients with chronic rejection stimulated PDGF-induced DNA synthesis of SMC in a dose-dependent manner, showing significant enhancement as compared with control transplant patients, normal subjects, and chronic HD patients. The supernatant itself did not significantly stimulate DNA synthesis of SMC. No significant in vitro stimulation of CsA on DNA synthesis was observed. The supernatant of T cells obtained from recipients undergoing chronic rejection with two DRB 1 mismatches showed significantly higher enhanced activity of PDGF-induced DNA synthesis than the supernatant from those recipients without mismatch of DRB 1. On the other hand, no significant correlation of the enhanced activity by T cell supernatant to HLA A and B mismatch numbers was observed. CONCLUSIONS: Growth factor-promoting factors(s) derived from activated T cells associated with MHC class II DR expression, which promotes PDGF-induced proliferation of SMC, exists in renal transplant patients with chronic renal allograft nephropathy, and is probably involved in arteriosclerosis of the graft kidney.     

肿瘤坏死因子相关凋亡诱导配体及其受体在烧伤大鼠胸腺组织中的表达

目的 了解肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）及其受体在严重烧伤大鼠胸腺组织细胞异常凋亡中的作用。方法 将50只Wistar大鼠随机分为假伤组（模拟烧伤）lO只和烧伤组40只（设伤后4、12、24、48h 4个时相点）。应用膜联蛋白A5-异硫氰酸荧光素／碘化丙啶双染法，观察大鼠胸腺组织中细胞凋亡的情况；反转录-聚合酶链反应和蛋白质印迹法检测TRAIL的死亡受体5（DR5）、DR4、诱骗受体1（DcR-1）、DcR2在大鼠胸腺组织中的表达。结果 与假伤组大鼠细胞凋亡率[（6．7±0．8）％]比较，烧伤组于伤后4h[（17．1±0．4）％]起增高，12h时[（25．2±1．1）％]达高峰，48h时仍明显高于假伤组（P〈0．05）。烧伤组大鼠胸腺组织中DR5的表达显著高于假伤组，DcR2的表达则显著低于假伤组；其余受体的表达组间相似。结论 严重烧伤后早期大鼠胸腺组织的细胞凋亡明显增加，且胸腺组织中DR5和DcR2的表达异常，提示TRAIL凋亡途径可能参与了病理性细胞凋亡过程。     

Plasminogen activator inhibitor-1 polymorphism is associated with progressive renal dysfunction after acute rejection in renal transplant recipients

BACKGROUND: Plasma level of plasminogen activator inhibitor (PAI)-1 is genetically determined by a polymorphism in the promoter region, involving two alleles, 4G and 5G. Plasma PAI-1 concentrations are higher in subjects homozygous for the 4G allele than other genotypes (5G/5G and 4G/5G). Such genetic variation in fibrinolytic system may affect the long-term renal transplant outcome. METHODS: We determined PAI-1 4G/5G-promoter genotype polymorphism among our renal transplant recipients between 1985 and 2001. Primary event was defined as doubling of baseline serum-creatinine level. RESULTS: Over a median period of 79 months, 130 patients with 132 kidney grafts were assessed. Baseline clinical variables were comparable among three genotype groups. There was no association between primary event and PAI-1 genotype among the entire cohort. However, among subjects with prior acute rejection episodes, those homozygous for 4G had significantly higher risk of serum creatinine doubling than the other two genotypes (relative risk 2.45, 95% confidence interval 1.19-5.04). PAI-1 genotype does not predict primary events in patients without rejection (relative risk 0.57, 95% confidence interval 0.07-4.17). CONCLUSIONS: PAI-1 4G/5G-promoter polymorphism modulates the risk of renal transplant outcomes after acute rejection(s). Recipients homozygous for PAI-1 4G allele have a higher risk of progressive renal damage after acute rejection episode(s). PAI-1 promoter polymorphisms are potentially important determinants of renal response to rejection.     

尿流式细胞学在诊断移植肾急性排斥反应中的应用价值

目的：探讨尿流式细胞学在诊断移植肾急性排斥反应中的临床应用价值。方法：对43例肾移植受者的116份尿样本进行尿流式细胞学分析，并将急性排斥组和肾功能稳定组的分析结果进行比较。结果：急性排斥反应组尿淋巴细胞总数以及HLA－DR^ 淋巴细胞数显著增多，与肾功能稳定组比较，P＜0．01，CD8^ 细胞亦增多（P＜0．05），而CD3^ ,CD4^ ,CD19^ 细胞数变化两组差异不显著（P＞0．05），在诊断移植肾急性排斥反应上，HLA－DR阳性样本和淋巴细胞数阳性样本的诊断敏感性和特异性分别达95．2％，90．5％，和92．6％，87．4％，结论：尿流式细胞学分析可反映移植肾内的免疫状态，尿淋巴细胞数的显著增多和尿HLA－DR^ 淋巴细胞增多可以作为诊断急性排斥反应的有意义指标。