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1.
目的:探讨抗可诱导共刺激分子(inducible costimilator,ICOS)单克隆抗体与小剂量环孢素A(cyclosporine,CsA)联用对同种异基因大鼠心脏移植后移植物生存质量和慢性排斥反应的影响。方法:建立大鼠腹腔异位心脏移植模型,术后随机分为同基因移植对照组和同种异基因移植试验组,其中试验组根据术后处理不同又分为安慰剂组、常规剂量CsA组、抗-ICOS-单抗组、小剂量CsA组和抗-ICOS-单抗联合小剂量CsA组,观察各组大鼠移植心脏的存活时间及移植心组织病理学变化,对移植心长期存活(〉100d)的受体,应用流式细胞仪检测其外周血CD4^+CD25^+调节性T细胞。结果:单独使用不同剂量CsA者移植心脏的存活时间较安慰剂组明显延长(P〈0.05);抗-ICOS-单抗联用小剂量CsA组移植心脏的存活时间较单用小剂量CsA组明显延长(P〈0.05);与安慰剂组相比,单用抗-ICOS-单抗组移植心脏存活时间差异无统计学意义(P〉0.05)。移植心长期存活受体中,与常规剂量CsA组比较,联合治疗组移植心慢性排斥损伤明显减轻,而外周血CD4^+CD25^+调节性T细胞比例有显著升高(P〈0.05)。结论:抗ICOS单抗加小剂量CsA联合免疫治疗,可有效延长大鼠移植心存活时间和减轻慢性排斥反应,CD4^+CD25^+调节性T细胞的高水平表达与诱导移植耐受、抑制慢性排斥反应有重要关联。  相似文献   

2.
目的 探讨不同剂量的强效免疫抑制剂环孢素(CsA)对同种异基因心脏移植大鼠急性排斥反应程度和血清吲哚胺2,3双加氧酶(IDO)活性的影响.方法 分别以SD和Wistar大鼠为供、受体,建立同种异基因大鼠颈部异位心脏移植模型.18只受体大鼠随机分为对照组、低剂量CsA组(CsA 2 mg·kg-1·d-1)和高剂量CsA组(CsA 15 mg·kg-1·d-1),每组6只.术后第7天,所有受体大鼠经腹主动脉采集血样后处死,取移植心脏制备组织学检查标本.ELISA法检测血清白介素2(IL-2)和γ干扰素(IFN-γ)水平;高压液相色谱法检测血清犬尿氨酸和色氨酸浓度,计算两者比值并以此估算IDO活性.移植心脏标本常规HE染色,采用Stanford标准进行急性排斥反应程度分级.结果 三组血清IL-2和IFN-γ水平以及IDO活性比较显示,对照组>低剂量CsA组>高剂量CsA组,差异均有统计学意义(P<0.05或P<0.01).三组移植心脏急性排斥反应程度分级结果显示,对照组>低剂量CsA组>高剂量CsA组,差异均有统计学意义(P<0.01).结论 CsA可明显减轻同种异基因大鼠移植心脏急性排斥反应程度并降低血清IDO活性,两者变化趋势一致且与CsA的使用剂量有关.提示血清IDO活性监测有可能成为一种无创性移植器官急性排斥反应及其程度的预测和评估方法.  相似文献   

3.
目的 探讨小剂量环孢素A(cyclosporine,CsA)联合眼镜蛇毒因子(cobra venom factor,CVF)对大鼠同种异体心脏移植急性排斥反应的影响.方法 采用改良Ono's 方法建立大鼠心脏移植排斥反应动物模型,将实验动物分为5组,每组9 只.A 组:对照组;B 组:半量CsA组;C 组 :全量CsA组;D组:CVF组;E组:半量CsA联合CVF组.分别在1、3、5、7 d从各组中取1只处死,其余5只观察移植心脏存活天数,应用HE染色进行供心排斥反应病理分级,免疫组织化学检查CD3 、CD4 、CD8 T淋巴细胞浸润情况,RT-PCR法检测供心IL-2、IL-10 mRNA表达水平.结果 A、B、C、D和E组大鼠移植心脏存活时间分别为(7.88±0.99)、(14.94±1.43)、(20.76±0.94)、(14.96±2.29)d和(31.10±3.36) d,与A组相比,各治疗组大鼠心脏存活时间均明显延长(P<0.01),E组移植心脏存活时间较B、C、D组明显延长(P<0.01).各实验组免疫排斥发生时间延后,排斥反应分级减轻,CD3 、CD4 、CD8 T淋巴细胞浸润减少,尤其C、E两组明显(P<0.01).A与D组IL-2 、IL-10 mRNA含量无明显差异(P>0.05),E组与B、C组比较,IL-2 、IL-10 mRNA含量也无明显差异(P>0.05).结论 CsA和CVF在抗急性排斥反应上具有协同效应,小剂量CsA联合使用 CVF 能增强抗排斥反应疗效,优于大剂量CsA单用组,CVF能单独或者协同CsA抑制T细胞的浸润,但CVF对排斥相关细胞因子的分泌无明显作用,也不加强CsA抑制细胞因子分泌的效应,其抗排斥反应的机制还需进一步探讨.  相似文献   

4.
目的 探讨不同剂量的强效免疫抑制剂环孢素(CsA)对同种异基因心脏移植大鼠急性排斥反应程度和血清吲哚胺2,3双加氧酶(IDO)活性的影响.方法 分别以SD和Wistar大鼠为供、受体,建立同种异基因大鼠颈部异位心脏移植模型.18只受体大鼠随机分为对照组、低剂量CsA组(CsA 2 mg·kg-1·d-1)和高剂量CsA组(CsA 15 mg·kg-1·d-1),每组6只.术后第7天,所有受体大鼠经腹主动脉采集血样后处死,取移植心脏制备组织学检查标本.ELISA法检测血清白介素2(IL-2)和γ干扰素(IFN-γ)水平;高压液相色谱法检测血清犬尿氨酸和色氨酸浓度,计算两者比值并以此估算IDO活性.移植心脏标本常规HE染色,采用Stanford标准进行急性排斥反应程度分级.结果 三组血清IL-2和IFN-γ水平以及IDO活性比较显示,对照组>低剂量CsA组>高剂量CsA组,差异均有统计学意义(P<0.05或P<0.01).三组移植心脏急性排斥反应程度分级结果显示,对照组>低剂量CsA组>高剂量CsA组,差异均有统计学意义(P<0.01).结论 CsA可明显减轻同种异基因大鼠移植心脏急性排斥反应程度并降低血清IDO活性,两者变化趋势一致且与CsA的使用剂量有关.提示血清IDO活性监测有可能成为一种无创性移植器官急性排斥反应及其程度的预测和评估方法.  相似文献   

5.
目的:探讨缺血再灌注损伤对移植心脏急性排斥反应的影响.方法:分别建立有IRI(同种系和异系)和避免IRI(同种系和异系)4种大鼠异位心脏移植模型,并设立空白对照组,于术后第7天取供心检测移植心脏,采用RT-PCR方法检测移植心脏MHC-2 mRNA、B7-1/B7-2 mRNA表达情况及应用免疫组织化学染色方法观察CD4+T细胞在供心的浸润情况.结果:同种系两组心脏移植研究表明,IRI增强了移植心脏的免疫源性,但CD4+T细胞浸润情况两组间无明显差异(P>0.05);结合同种异系两组心脏移植研究表明,同种异系移植心脏的免疫源性比同种系两组心脏移植均明显增强,且IRI的异系组增加更明显,CD4+T细胞浸润情况更显著(P<0.05).结论:IRI促进移植心脏排斥反应的发生,不停跳心脏移植由于避免了IRI,因此有助于减轻急性排斥反应发生的强度或延缓急性排斥反应的发生.  相似文献   

6.
目的探讨脾切除对同种异体心脏移植大鼠外周血CD4+、CD25+T淋巴细胞及Foxp3的影响及意义。方法行Wistar(供体)到SD(受体)大鼠的腹部异位心脏移植并按实验设计行实验动物分A组(对照组)、B组(单纯脾切除组)、C组(单纯心脏移植组)、D组(心脏移植+脾切除组)四组。以光镜、电镜观测心肌的病变特点、以流式细胞术检测外周血CD4+、CD25+T淋巴细胞的动态变化,RT-PCR检测CD4+、CD25+T淋巴细胞的功能基因及Foxp3的表达情况并观测大鼠移植心脏的存活情况。结果 C、D组移植心脏的心肌病理及亚显微结构改变均在术后第5天最重,第7天减轻,且D组的病理改变明显轻于C组。D组移植心脏存活时间为:(17.63±4.54)d(n=12),较C组存活时间[(7.47±2.24)d(n=12)]明显延长(P〈0.05)。CD4+、CD25+T淋巴细胞的数量与其功能基因及Foxp3在A组中无明显变化,在B组中术后第3、5天升高,术后第7天恢复正常,在C组、D组中术后四个时间点的变化有显著差别且成正相相关,D组CD4+、CD25+T淋巴细胞的数量与功能基因及Foxp3在术后分别为:3d(13.60±3.22、31.9±5.5)、5d(9.93±1.26、29.8±3.3)、7d(9.49±0.95、27.3±2.9)明显高于C组:3d(4.83±0.94、12.3±3.3)、5d(3.69±0.63、8.0±1.8)、7d(3.29±0.60、4.2±1.5)(P均〈0.01)。结论脾切除具有诱导心脏移植大鼠免疫耐受形成的作用,在此过程中心脏移植大鼠CD4+、CD25+T淋巴细胞数量增加及其功能基因及Foxp3表达上调,且与急性排斥反应成负相关,提示CD4+、CD25+T淋巴细胞的数量与功能变化可能参与免疫耐受的形成。  相似文献   

7.
目的 观察供体脾细胞(SPC)与环磷酰胺(CP)联合预处理对大鼠移植心脏存活时间的影响.方法 应用大鼠颈部心脏移植模型,实验分为对照组(未干预组)、CsA组、SPC CP组.CsA组心脏移植后予环孢霉素A(CsA)10 mg/kg,SPC CP组采用供体SPC和CP预处理移植受体,然后行大鼠颈部心脏移植术.观察移植心脏存活情况及组织病理变化.结果 对照组、CsA组、SPC CP组移植心脏存活时间分别为(7.2±2.4)、(15.8±4.3)、(30.4±10.7)天;组织病理检查显示,经SPC PC预处理的移植心脏排斥反应明显减弱.结论 SPC和CP预处理可以诱导受体对移植物的免疫耐受,延长移植心脏的存活期,效果优于CsA.  相似文献   

8.
目的:运用基因芯片技术分析同种异基因大鼠心脏移植后急性排斥反应的基因表达谱. 方法:建立大鼠颈部心脏移植模型,以同种同基因和异基因移植动物作为对照,术后5 d移植心脏中抽提总RNA,纯化后的mRNA进行逆转录制备杂交探针,应用含有4 096个靶基因的表达谱芯片对两组移植心脏组织进行差异表达谱分析.结果:在同种异基因心脏移植术后差异表达基因共有210条(下调96条,上调114条);其中已知基因有33条(下调13条,上调20条);未知基因177条(下调83条,上调94条),其中有15条已知基因(上调2条,下调13条)尚未见报道.结论:运用基因芯片技术研究同种异基因心脏移植术后急性排斥相关基因,可为进一步研究其发病机制和治疗提供新思路.  相似文献   

9.
目的探讨腺病毒介导CD40Ig基因(AdCD40Ig)在大鼠肝脏移植中的作用。方法随机将供受体大鼠分4组,A:同基因移植组,B:免疫排斥组,C:AdLacZ对照组,D:基因治疗组。观察大鼠存活时间,CD40Ig、细胞因子水平和移植肝病理情况。结果 D组存活时间长于B、C组(P<0.05);CD40Ig浓度于术后7天达高峰;D、A组IL-2、IFN-γ水平较B、C组明显降低(P<0.05),D组IL-10较其他组明显增加(P<0.05);B、C两组术后出现中、重度排斥反应,汇管区淋巴细胞浸润明显,D组汇管区轻度炎症,无明显血管损伤证据,病理评级较B、C组有统计学意义(P<0.05)。结论 CD40Ig通过阻断CD40/CD40L通路,可延长移植肝存活时间,在受体内长期表达,减少汇管区淋巴细胞浸润,影响相关细胞因子的表达,对大鼠肝脏急性排斥反应有抑制作用。  相似文献   

10.
目的研究Foxp3基因转染的受体na ve CD4 CD25-T淋巴细胞对小鼠同种异体心脏移植物存活的影响。方法将Foxp3重组逆转录病毒载体转染的CD4 CD25-T细胞于术前1d经尾静脉输入受体体内。实验分为3组:A组:Foxp3组,术前输入转染PLXSN-mFOXP3-IRES2-EGFP的受体CD4 CD25-T细胞;B组:调节性T细胞组,术前输入受体CD4 CD25 调节性T细胞;C组:空白对照组术前没有加任何干扰措施。术后第3天、第7天各组随机取2只小鼠,进行病理学检查。其余小鼠每日观察心脏移植物存活情况。结果4组移植物的存活时间分别为:A组(56.7±13.5)d(n=15),B组(59.1±11.5)d(n=15),C组(14.0±4.4)d(n=15)。A、B组移植物的存活时间较对照组显著延长,差异有统计学意义(P<0.01),但A、B两组之间差异无统计学意义(P>0.05),病理检查显示A、B组移植物排斥反应轻于C组。结论转染Foxp3基因的小鼠na ve CD4 CD25-T细胞,可以明显延长小鼠异位心脏移植物存活时间,其能力与自然发生的CD4 CD25 调节性T细胞相当。  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP). Methods:Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin(HE) staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results:Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin(9/9 cases), AAT(9/9 cases), NSE(9/9 cases), ACT(7/9 cases), CK20(2/9 cases), CgA(1/9 cases), S-100(3/gcases), PR(4/gcases), Syn(3/9 cases) and CD56(5/9cases), negative in CEA and ER. Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.  相似文献   

18.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

19.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

20.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

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