抗内毒素Fab'对严重烧伤早期炎症细胞因子的影响

目的 观察抗内毒素Fab'对严重烧伤早期肠源性内毒素血症小鼠肠道损伤的保护作用.方法 采用严重烧伤早期肠源性内毒素血症小鼠模型,分为烧伤组、治疗组及对照组,分别于6、12、24、48 h四个时相点测定血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-lβ、IL-10的浓度.结果 与正常对照组比较,烧伤后血清TNF-α、IL-1β、IL-10水平增高,差异有统计学意义(P<0.01);治疗组血清TNF-α、IL-1β、IL-10水平较烧伤组显著降低(P<0.01).病理检查结果提示治疗组较烧伤组肠黏膜损伤明显减轻.结论 抗内毒素Fab'能抑制内毒素所诱导的TNF-α、IL-1β产生,同时调节血清中的IL-10水平,减轻内毒素对机体的损害,从而起到对严重烧伤后肠源性脓毒症的防治作用.     

The surface antigen CD45R identifies a population of estrogen-regulated murine marrow cells that contain osteoclast precursors

We examined the osteoclastogenic potential of murine bone marrow cells that were fractionated according to their expression of the surface antigen CD45R. Osteoclast-like cells (OCL) with many authentic osteoclast characteristics readily formed in purified CD45R⁺ murine bone marrow cell cultures after treatment with receptor activator of nuclear factor κB ligand (RANKL) and M-CSF. Ovariectomy (Ovx) caused a 1.5- to 2-fold increase in OCL number in unfractionated and CD45R⁺ murine bone marrow cell cultures without affecting OCL formation in CD45R⁻ marrow cells. Limiting dilution assays confirmed that Ovx caused an increase in osteoclast precursor cell number in CD45R⁺ but not CD45R⁻ cells. Mice deficient in the type 1 IL-1 receptor (IL-1R1 KO) do not lose bone mass after Ovx. We found that unfractionated, CD45R⁺, and CD45R⁻ bone marrow cells from IL-1R1 KO mice showed no increase in OCL formation in vitro after Ovx. In both the wild-type (WT) and the IL-1R1 KO mice Ovx was associated with a 2-fold increase in pre-B-lymphocytes. About 1.3–3.5% of murine marrow cells expressed surface RANK (the receptor for RANKL) while about 11.9–15% of murine bone marrow cells expressed c-Fms (the receptor for M-CSF). There was little effect of Ovx on cells expressing either RANK or c-Fms. These results demonstrate that CD45R expression identifies a subset of murine bone marrow cells whose ability to form OCL in vivo is regulated by estrogen in WT but not IL-1R1 KO cells. The effects of estrogen on bone mass may be related to these responses.     

Simvastatin treatment improves survival in a murine model of burn sepsis: Role of interleukin 6

Infection is the most common and most serious complication of a major burn related to burn size. Recent studies have demonstrated that statin treatment can decrease mortality in murine or human sepsis. In the current study mice were anesthetized and subjected to a dorsal 30% TBSA scald burn. Simvastatin or placebo were administered by intraperitoneal injection once daily or every 12 h. On post burn day 7 cecal ligation and puncture with a 21-gauge needle (CLP) was performed under ketamine/xylazine anesthesia, the two different dosing schedules were continued and survival was monitored. In other groups of mice, interleukin-6 (IL-6) levels in blood were measured in mice at 7 days after injury. A simvastatin dependent improvement in survival was observed in the burn sepsis model. This protection was found to be dose and time dependent. In addition, statin treatment reduced the elevation in IL-6 levels of mice burned 7 days previously. However, IL-6 levels in burned mice with or without statin treatment were elevated by CLP to the same degree. The results of these studies suggest that statin treatment reduces mortality in mice with burns and CLP and that this effect may not be mediated via IL-6 levels.     

合并前列腺炎症的良性前列腺增生组织中Integrinα2β1/CD133表达及其意义

目的：探讨合并前列腺炎症的良性前列腺增生（BPH）组织中Integrinα2β1/CD133表达及其意义。方法：收集56例行经膀胱前列腺摘除手术的BPH患者的前列腺标本,常规HE染色后观察其合并炎症情况,其中单纯BPH（24例）为A组,合并前列腺炎症的BPH（32例）为B组。采用免疫组化SP法及Western印迹法检测Integrinα2β1/CD133在两组前列腺组织中表达差异。Image-ProPlus 6.0图像分析软件对结果进行分析。结果：免疫组化Mattern积分结果显示：两组中Integrinα2β1/CD133表达有显著差异（P〈0.05）。Western免疫印迹显示：B组Integrinα2β1平均相对光密度值高于A组[（0.29±0.18）vs（0.04±0.03）],P〈0.05;B组CD133平均相对光密度值高于A组[（0.08±0.07）vs（0.002 0±0.001 8）],P〈0.05。提示B组中Integrinα2β1/CD133表达较A组显著升高。结论：炎症可以促进BPH组织中Integrinα2β1/CD133蛋白表达表达。     

急性坏死性胰腺炎肺组织炎性介质mRNA表达与肺损伤的关系

目的 探讨急性坏死性胰腺炎(ANP)大鼠肺组织白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及细胞间黏附分子(ICAM-1)等炎性介质mRNA表达与肺损伤的关系.方法 33只Wistar大鼠随机分为正常对照和胰腺炎不同时间点(1、4、12和24 h)各组,应用3.5%牛磺胆酸钠逆行胰胆管注射制备ANP模型.采用RT-PCR法检测ANP肺组织IL-6、TNF-α及ICAM-1 mRNA表达,同时观察血淀粉酶及脂肪酶、胰腺和肺组织湿/干重比率及病理改变.结果 造模ANP 1 h后肺组织IL-6、TNF-α及ICAM-1 mRNA水平(1.25±0.16、0.33±0.09及082±0.03)较正常对照组(0.07±0.02、0.06±0.02及0.41±0.04)表达增高(P<0.05),并持续升高至12及24 h(分别为1.674±0.14、0.99±0.11、1.17士0.05及1.87±0.05、0.96士0.06、1.11士0.04),同时伴有肺组织病理损害,其严重程度与肺TNF-α及ICAM-1 mRNA表达、肺组织湿/干重比率与TNF-α、IL-6、ICAM-1 mRNA表达的相关系数分别为0.93及0.70(P<0.05).结论 大鼠ANP早期肺组织IL-6、TNF-α及ICAM-1mRNA即过度表达,肺IL-6、TNF-α及ICAM-1mRNA过度表达是ANP肺损害发生的原因之一,肺损伤严重程度与IL-6、TNF-α及ICAM-1mRNA表达的高低有关.     

Combined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation.

Current immunosuppressive strategies for transplantation have failed to achieve long-term graft survival. In this study, we investigate the effects of combined treatment with triptolide (TPT) and rapamycin (Rapa) on graft survival as well as changes in pathology and immunological responses. Heterotopic heart transplantation was performed. TPT and Rapa were administered either alone or in combination. The mean survival time (MST) for the cardiac allografts in animals receiving the combination of TPT and Rapa was 93.5 +/- 6.7 days compared to treatment with TPT (MST: 23.5 +/- 5.3 days), Rapa (22 +/- 1.3 days) alone or no treatment (7.66 +/- 0.8 days). Histopathological evaluation showed that inflammatory cell infiltration was markedly reduced in grafts with combined treatment groups. Down-regulation of CCL19, CCR5, CCR7, interferon gamma and interleukin (IL)-12 in the combination treatment was accompanied by increased expression of IL-4, IL-10 and CD4(+)CD25(+)Foxp3(+) regulatory T (Tr) cells in spleen. Finally, dendritic cell (DC) maturation was impaired by treatment with TPT/Rapa. Our results demonstrate that combination therapy with TPT and Rapa markedly prolongs cardiac allograft survival. This effect is accompanied by inhibition of DCs maturation, conditioning DCs to adopt tolerogenic phenotype, and the expansion of Tr cells. These results add weight to the application of combination therapy in transplantation.     

Anti-inflammatory effects on ischemia/reperfusion-injured lung transplants by the cluster of differentiation 26/dipeptidylpeptidase 4 (CD26/DPP4) inhibitor vildagliptin

Objectives

We showed previously that stromal cell?derived factor 1 (SDF-1) is a substrate of cluster of differentiation 26/dipeptidylpeptidase 4 (CD26/DPP4) and exerts regenerative properties on acute lung ischemia-reperfusion injury on CD26/DPP4 inhibition. Here, we extend our studies to test whether an intermediate recovery of lung transplants from ischemia/reperfusion injury by CD26/DPP4 inhibition can be achieved for up to 14 days.

15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis.

BACKGROUND: Here we compare the efficacy of cyclophosphamide (CYC) for treatment of crescentic nephritis (CGN) with the newer immunosuppressants 15-deoxyspergualin (DSG) and mycophenolate mofetil (MMF) in SCG/Kj mice, an inbred mouse strain that spontaneously develops CGN, systemic necrotizing vasculitis and antineutrophil cytoplasmic antibodies (ANCAs). METHODS: Mice were randomly assigned to intraperitoneal treatment with either DSG (2 mg/kg/day), CYC (50 mg/kg/week), MMF (60 or 100 mg/kg/day) or vehicle (VEH, dextrose 5% 0.3 ml/day) beginning at the 10th week of life. ANCA, blood urea nitrogen (BUN) and proteinuria were determined in all animals regularly, and survival was calculated. Renal histology was obtained in the 18th week of life in the MMF- or VEH-treated groups and in the 24th week in DSG- or CYC-treated animals. RESULTS: Mean survival in VEH-treated animals was 123 days. At that point, survival was 100% in the CYC- or DSG-treated animals (P<0.001). Survival in the MMF group (pooled data) was not significantly different from the VEH-treated animals [MMF, 117 days (95% CI 108-127)]. BUN (18th week, CYC 43+/-9 mg/dl and DSG 36+/-6 mg/dl vs VEH 73+/-28 mg/dl, P<0.001, MMF 66+/-26 mg/dl), 24 h proteinuria (18th week, CYC 0.4+/-0.2 mg and DSG 0.7+/-0.6 mg vs VEH 2.7+/-3 mg, P<0.001, MMF 2.2+/-3 mg) crescent formation (18th week, VEH 42+/-9%, MMF 39+/-11%; CYC 5+/-2% and DSG 22+/-7% vs VEH, P<0.05), glomerular immune complex deposition, and ANCA formation were significantly improved in CYC- and DSG- but not in MMF-treated animals when compared with controls. CONCLUSION: DSG and CYC, but not MMF, prolong life, limit renal damage and prevent autoantibody formation in SCG/Kj mice.