紫杉醇抑制大鼠移植动脉硬化的作用

目的 探讨紫杉醇防治大鼠移植动脉硬化的作用及其机制.方法 采用大鼠胸腹主动脉移植模型,同系移植组供、受者均为Wistar大鼠,同种移植组和紫杉醇治疗组的供者均为Wistar大鼠,受者均为SD大鼠,紫杉醇治疗组术后第1～14天腹腔注射紫杉醇2 mg·kg-1·d-1,其它组则每日腹腔注射相同体积的生理盐水.术后30 d取出移植动脉,光镜下观察移植动脉的内膜增生情况,同时采用电镜和末端脱氧核苷酸转移酶介导的三磷酸脱氧尿嘧啶缺口末端标记法(TUNEL)检测血管平滑肌细胞(VSMCs)凋亡情况.结果 术后30 d,同系移植组血管形态基本保持正常;同种移植组血管内膜明显增厚,内外膜有大量炎症细胞浸润,管腔显著狭窄;紫杉醇治疗组移植血管内膜无明显增厚,内外膜炎症细胞浸润较同种移植组明显减轻,管腔无狭窄.电镜及TUNEL检测结果显示紫杉醇治疗组VSMCs凋亡较其它两组明显增高.结论 紫杉醇能明显抑制移植动脉的硬化,其作用机理可能与其诱导移植动脉VSMCs凋亡有关.     

反义寡核苷酸防治移植物动脉硬化的作用

目的　探讨防治移植物动脉硬化的途径。方法　通过大鼠胸腹主动脉移植简化模型 ,用各种增殖细胞核抗原 (PCNA)寡核苷酸在脂质体介导下转染大鼠胸主动脉后 ,移植到大鼠腹主动脉 ,于术后 15、3 0和 60d取移植动脉作病理学检查及PCNA逆转录PCR检测。结果　病理学结果示 ,在 3个时相点 ,反义寡核苷酸组移植动脉再狭窄率 (8.3 %、12 .4%、19.5 % )均显著低于对照组 (P <0 .0 5 )。逆转录PCR结果显示 ,在 3个时相点 ,反义寡核苷酸组PCNAmRNA的表达(5 9.2 4、80 .16、18.5 8)均明显低于对照组 (P >0 .0 5 )。结论　PCNA反义寡核苷酸可明显抑制移植动脉PCNA蛋白的表达 ,抑制动脉内膜增生 ,防治移植物动脉硬化。     

大鼠腹腔心脏移植术后移植物血管病模型的建立

目的探讨建立大鼠腹腔心脏移植物血管病动物模型的方法。方法将40只W istar大鼠和40只SD大鼠随机配对分为对照组和实验组,建立大鼠的异位心脏移植;对照组不注射环孢霉素A(C sA),实验组腹腔注射小剂量的C sA,两组分别于移植术后2周和4周切取移植心脏,在光学显微镜下观察移植心脏冠状血管的改变。结果对照组术后2周和4周冠状血管内膜无变化;实验组术后2周冠状血管内膜增厚,4周后冠状血管内膜成同心圆样改变,管腔明显狭窄,出现移植后移植物血管病改变。结论该模型是一种可靠的移植物血管病的动物模型。     

冬虫夏草提取物抑制大鼠移植物血管病的实验研究

目的 探讨冬虫夏草提取物抑制大鼠移植动脉硬化的效果及其机制.方法 制备大鼠腹主动脉移植模型,分为4组进行实验:同系对照组供、受者均为Lewis大鼠,生理盐水灌胃60d;同种对照组,以Brown-Norway大鼠(BN大鼠)为供者,Lewis大鼠为受者,生理盐水灌胃60d;低剂量实验组,以BN大鼠为供者,Lewis大鼠为受者,以冬虫夏草提取物(1.5 g·kg-1·d-1)灌胃60 d;高剂量实验组,以BN大鼠为供者,Lewis大鼠为受者,以冬虫夏草提取物(3.0g·kg-1·d-1)灌胃60d.于移植后60 d取移植动脉,HE染色,进行病理学观察;免疫组织化学和蛋白质印迹法检测血管内皮生长因子(VEGF)和血小板衍生生长因子BB(PDGF-BB)在移植动脉中的表达.酶联免疫吸附试验检测受鼠血清中VEGF和PDGF- BB含量.结果 同系对照组移植动脉形态正常;同种对照组移植动脉呈移植物血管病表现,血管内膜显著增厚;2个实验组移植动脉呈内膜炎症改变,内膜厚度与同种对照组相比,差异有统计学意义(P＜0.05).同种对照组移植动脉中VEGF和PDGF-BB的表达高于同系对照组(P＜0.05);2个实验组移植动脉中VEGF和PDGF-BB的表达低于同种对照组(P＜0.05).同系对照组受鼠血清中几乎无VEGF和PDGF-BB;同种对照组血清中VEGF和PDGF-BB浓度高于同系对照组(P＜0.05);和同种对照组相比较,2个实验组血清VEGF和PDGF-BB浓度较低(P＜0.05).结论 冬虫夏草提取物能明显抑制动脉内膜的增生,可缓解慢性排斥反应所致的移植动脉硬化,这种保护作用可能与下调VEGF和PDGF-BB表达有关.     

人arresten重组蛋白对移植物动脉硬化的抑制作用

目的观察人arresten重组蛋白对移植物动脉硬化的抑制作用。方法用pRSET原核表达系统表达并纯化人arresten重组蛋白。建立腹主动脉移植大鼠模型，将受体鼠分为同系动脉移植组、异系移植对照组和异系移植实验组。自术后第3天起，皮下给予arresten重组蛋白（每日5mg／kg体重）处理。8周后取移植动脉组织标本，进行病理组织学观察与免疫组织化学染色，分析移植动脉新生内膜增生及新生内膜细胞α-平滑肌肌动蛋白（α-SMA）和PCNA的表达。结果异系移植组移植动脉新生内膜中α-SMA表达阳性平滑肌细胞大量增生，致动脉内膜增厚，管腔狭窄。异系移植实验组移植动脉内膜增生受到明显抑制，新生内膜面积（0．14±0．03）mm^2。及新生内膜／中膜面积比（0．807±0．073）均显著低于异系移植对照组[（0．33±0．07）mm^2，（1．794±0．089），P〈0．01]；并且异系移植实验组移植动脉新生内膜细胞PCNA标记指数（31．72±5．26）％显著低于异系移植对照组（69．53±4．38）％（P〈0．01）。结论人arresten重组蛋白能有效抑制移植物动脉硬化的发生发展，在抗移植物慢性排斥反应方面显示出良好的应用前景。     

乙酰肝素酶诱导大鼠移植动脉硬化的作用

目的探讨乙酰肝素酶在同种异体血管移植中的作用及其与移植动脉硬化的关系。方法实验分为两组,实验组:以Wistar大鼠为供者,SD大鼠为受者,取供者肾下腹主动脉(长约1 cm),正位替换受者同部位主动脉,建立腹主动脉移植模型。对照组:仅将SD大鼠相应的腹主动脉切断后再行原位吻合。术后60 d时,应用逆转录聚合酶链反应、免疫组织化学法和计算机图像分析方法分别检测各组腹主动脉的乙酰肝素酶水平、炎性细胞浸润程度(ED1、CD4细胞)、腹主动脉内膜厚度及管腔面积。结果实验组移植的腹主动脉中乙酰肝素酶表达较对照组明显增加;实验组ED1及CD4细胞阳性表达率分别为(44.8±12.5)%和(37.6±7.9)%,对照组分别为(8.9±3.7)%和(10.3±5.6)%,两组相比,差异有统计学意义(P<0.01)。实验组移植腹主动脉内膜厚度增加,管腔面积减少,与对照组比较,差异有统计学意义(P<0.05)。结论免疫炎性细胞可通过激活乙酰肝素酶介导移植的腹主动脉损伤,促进动脉硬化形成。     

联合转染eNOS基因反义ET核酸对自体移植静脉内膜增生的影响

目的;探讨联合转染eNOS基因和反义ET核酸对自体移植静脉内膜增生的影响。方法：制作20只自体颈静脉腹主动脉移植Wistar大鼠模型,实验组,对照组各10只,实验组移植血管行腺病毒介导的eNOS溶液浸泡和反义ET核酸凝胶涂布,对照组仅行空载腺病毒溶液浸泡和凝胶兴布。术后2周取出移植血管,利用病理学,免疫组织化学,RT－PCR方法检测移植血管内膜厚度,管腔狭窄度,内膜VSMC数及PCNA阳性表达,血管ETmRNA,eNOSmRNA表达情况。结果：实验组移植血管内膜厚度,管腔狭窄及VSMC数均较对照组减小或减少,PCNA阳性表达及ETmRNA表达较对照组减少,而eNOSmRNA表达则明显增加。结论;联合转染NOS基因和反义ET核酸可有效地抑制移植静脉内膜的增生,是一种有效地防治移植静脉再狭窄的基因疗法。     

腹主动脉移植后小鼠外周血内皮祖细胞数量的动态变化及意义

目的 观察腹主动脉移植后小鼠移植物动脉硬化的病变过程及外周血内皮祖细胞(EPC)数量的动态变化,探讨EPC与动脉内膜损伤和修复的相互关系.方法 以C57BL/6小鼠和Balb/c小鼠为供、受者,建立腹主动脉原位移植后移植性模型.术后3 d、2周、4周、6周,观察移植动脉病理改变,并采用计算机图像分析系统分析移植血管内膜增生情况.使用流式细胞仪监测术后外周血中EPC数量的变化.结果 术后3 d,移植动脉内皮细胞损伤,并伴有明显的炎症细胞浸润.术后2周,即可观察到移植动脉新生内膜形成,存在急性排斥反应;术后4周、6周内膜厚度逐渐增生,移植动脉管腔明显狭窄.术后早期外周血中EPC的数量增多,3 d时达到高峰,此后迅速减少,术后14和28 d时,显著低于术前水平(P＜0.05).结论 通过同种小鼠腹主动脉原位移植可成功复制出移植物动脉硬化的病变特点;外周血中EPC的数量与移植动脉内膜损伤的修复密切相关,可能成为移植物动脉硬化的发病指标和干预靶点.     

维拉帕米抑制大鼠心脏异位移植术后冠状血管内膜增厚

目的观察钙离子阻滞剂维拉帕米对心脏异位移植术后冠状血管内膜的影响。方法选用健康成年SD大鼠160只,随机平均分为对照组、实验1组、实验2组和实验3组。建立大鼠同种腹腔异位心脏移植模型。从移植当日到术后第9d,所有大鼠均接受环孢素A治疗,按5mg·kg-1·d-1腹腔注射,共10d;实验1、2、3组术后当天起加用维拉帕米,其剂量分别为0.1mg/kg、0.5mg/kg、1.0mg/kg,均为2次/d,连用3个月。移植后60d和90d切取移植心脏,将每例心尖组织进行HE和弹力纤维染色,根据移植心脏心尖部冠状动脉平均内膜增厚和管腔狭窄程度判定心脏移植物血管病变。结果对照组冠状血管狭窄程度较实验组明显加重,组间比较,差异有统计学意义。结论维拉帕米对大鼠移植心脏冠状血管内膜增厚有明显抑制作用。     

腹主动脉移植后小鼠外周血内皮祖细胞数量的动态变化及意义

目的 观察腹主动脉移植后小鼠移植物动脉硬化的病变过程及外周血内皮祖细胞(EPC)数量的动态变化,探讨EPC与动脉内膜损伤和修复的相互关系.方法 以C57BL/6小鼠和Balb/c小鼠为供、受者,建立腹主动脉原位移植后移植性模型.术后3 d、2周、4周、6周,观察移植动脉病理改变,并采用计算机图像分析系统分析移植血管内膜增生情况.使用流式细胞仪监测术后外周血中EPC数量的变化.结果 术后3 d,移植动脉内皮细胞损伤,并伴有明显的炎症细胞浸润.术后2周,即可观察到移植动脉新生内膜形成,存在急性排斥反应;术后4周、6周内膜厚度逐渐增生,移植动脉管腔明显狭窄.术后早期外周血中EPC的数量增多,3 d时达到高峰,此后迅速减少,术后14和28 d时,显著低于术前水平(P＜0.05).结论 通过同种小鼠腹主动脉原位移植可成功复制出移植物动脉硬化的病变特点;外周血中EPC的数量与移植动脉内膜损伤的修复密切相关,可能成为移植物动脉硬化的发病指标和干预靶点.     

选择性5-HT2A受体拮抗剂沙格雷酯延缓大鼠移植动脉急性排斥反应后纤维化

目的 研究选择性5-羟色胺2A(5-HT2A)受体拮抗剂沙格雷酯延缓大鼠移植动脉急性排斥反应后纤维化的作用。方法 实验分为3组,同种移植对照组（供、受者分别为Wistar大鼠和SD大鼠）、同系移植对照组（供、受者均为SD大鼠）和实验组（供、受者分别为Wistar大鼠和SD大鼠）,建立大鼠腹主动脉移植急性排斥反应后纤维化模型。术后各组大鼠喂养条件相同,仅实验组大鼠每天给予沙格雷酯灌胃,25 mg/kg。术后第14天和第60天对移植动脉行病理组织学及免疫组织化学检测,观察移植动脉内膜增生情况以及增殖细胞核抗原(PCNA)和平滑肌肌动蛋白(α-SMA)的表达情况。结果 所有移植手术均获成功。术后第14天时,同种移植对照组移植动脉出现典型的急性排斥反应改变。术后第60天,同种移植对照组、同系移植对照组和实验组内膜指数分别为(62.41±6.54)％、(0.94±0.33)％和(16.71±3.94)％,3组间内膜指数的两两比较,差异均有统计学意义(P＜0.05); PCNA和α-SMA细胞阳性率分别为(0.99±0.54)％和(0.79±0.33)％、(22.43±3.40)％和(23.70±2.78)％及(7.37±4.61)％和(8.21±3.11)％,3组间PCNA阳性率的两两比较及α-SMA阳性率的两两比较,差异均有统计学意义(P＜0.05)。结论 大鼠移植动脉急性排斥反应后可继发严重纤维化,沙格雷酯可显著延缓急性排斥反应后纤维化的发生、发展,其作用机制可能与下调PCNA和α-SMA的表达有关。     

Effect of a novel inducible nitric oxide synthase inhibitor in prevention of rat chronic aortic rejections

BACKGROUND: Cytotoxic nitric oxide (NO) is produced during ischemia-reperfusion injury and acute and chronic rejection in allografts by expression of inducible (i) NO synthase (NOS). Therefore, continuous inhibition of iNOS may prevent early graft dysfunction and immune injury (rejection) and consequently improve graft survival. FR260330 is a potent and selective inhibitor of iNOS activity that works by preventing iNOS monomers from dimerization. In this study, the authors evaluated the effect of FR260330 in prevention of chronic rejection in a model of rat aortic allografts. METHODS: Male Lewis (LEW, RT1l) rats received male ACI (RT1a) aorta allografts or LEW aorta isografts. Fourteen groups (n > or = 6) were involved in this study. FR260330, tacrolimus, or both were administered orally for 14 or 90 days, according to protocol. The degree of intimal proliferation of graft aorta was determined by a computerized image system. RESULTS: Both low and high doses of FR260330- or tacrolimus-treated grafts showed significantly decreased intima/(intima+media) ratios at day 90 compared with placebo controls. Combination therapy of low-dose FR260330 with low-dose tacrolimus produced a significant decrease of intima/(intima+media) ratios with intact endothelium compared with placebo controls. Anti-alpha-actin immunohistochemical staining demonstrated that one of the mechanisms of intimal proliferation is related to migration of vascular smooth muscle cells. CONCLUSIONS: A selective inhibitor of NOS, FR260330 plays a protective role in chronic aortic allograft rejection in the rat. Combination therapy of low-dose FR260330 with tacrolimus produces significant protection of immune injury and may serve to improve long-term graft survival and function.     

The combined use of prostaglandin I2 analogue (OP-2507) and thromboxane A2 synthetase inhibitor (OKY-046) strongly inhibits atherosclerosis of aortic allografts in rats

BACKGROUND: Atherosclerosis is the main lesion in allografts undergoing chronic rejection. We investigated the effect of OP-2507 (prostaglandin I2 analogue) and OKY-046 (thromboxane A2 synthetase inhibitor) on graft atherosclerosis morphologically and the production of eicosanoids in grafts in a rat aortic allograft model. METHODS: Abdominal aortic allografts of Lewis (RT-1(l)) rats were transplanted orthotopically into fully major histocompatibility complex mismatched Wistar King A/Qdj (RT-1(u)) rats that were subcutaneously administered OP-2507 (0.1 mg/kg/d) or OKY-046 (125 mg/kg/d), or both, with an osmotic pump. Four, 8, or 12 weeks later, the grafts were harvested and examined histologically, and the concentration of eicosanoids in the grafts were analyzed. RESULTS: Lewis aortic allografts in Wistar King A recipients with no treatment displayed atherosclerosis, which involved gradual intimal thickening and medial thinning with continuous inflammation in adventitia. Neither OP-2507 nor OKY-046 treatment affected the intensity of adventitial inflammation. Although inhibition of medial thinning or a decrease in medial nuclear density was not observed, OKY-046 administration alone significantly inhibited an increase in intimal thickness. OP-2507 administration alone significantly inhibited a decrease in medial nuclear density and intimal thickening. Combined treatment with OP-2507 and OKY-046 further decreased the alteration of media and intima. The ratio of thromboxane B2 and 6-keto-prostaglandin F(1alpha) in the grafts was significantly reduced by OKY-046 but not by OP-2507 alone. CONCLUSIONS: We have demonstrated that atherosclerosis in aortic allografts is inhibited by the continuous administration of either OP-2507 or OKY-046, and a combination of both agents strongly increases this inhibitory effect. Amelioration of balance in eicosanoid production in the grafts by the use of thromboxane A2 synthetase inhibitor and the simultaneous usage of stable prostaglandin I2 analogue may be a strategy for preventing atherosclerosis that results from chronic rejection.     

The myofibrosis mechanism of differentiation growth factor-8 on rat abdominal aorta grafts

OBJECTIVE: The objective of this study was to investigate the role of differentiation growth factor-8 (GDF-8) in inhibiting myofibrosis of abdominal aorta grafts. METHODS: Male Spague-Dawley (SD) rats that received abdominal aorta grafts from male Wistar rats were randomly divided into 2 groups: prolonged cold ischemia (PCI) and control groups. Hematoxylin-eosin (HE) staining was performed to examine aortic graft morphology and to measure neointimal thickness. RT-PCR demonstrated the expression of GDF-8. Immunohistochemical staining (IHC) was performed to detect the expression of Smad4, a pivotal molecule of the transforming, growth factor-beta (TGF-beta)/Smad signal pathway. RESULTS: The intimal thickness increased by 14 days following transplantation in the PCI group (P<.05), reaching 381.952+/-44.334 microm at 28 days, which was higher than that of the control group (56.898+/-17.543 microm; P<.05). The GDF-8 expression in the PCI group was only 3.6%-33.8% of that among the control group. There was a much higher expression of Smad4 on the endothelium of the PCI than the control group at the same time. CONCLUSIONS: Prolonged cold ischemia accelerated grafts myofibrosis by down-regulating the expression of GDF-8, which plays a key role in the myofibrosis process of rat abdominal aortic grafts.     

Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting

BACKGROUND: Fucoidan, a new low molecular weight sulfated polysaccharide (LMWF), has previously been shown to mobilize bone marrow-derived progenitors cells via stimulation of stromal derived factor (SDF)-1 release. Mobilized progenitor cells have been suggested to repair intimal lesions after immune-mediated endothelial injury and thus prevent intimal proliferation. The aim of this study was to evaluate the effect of LMWF treatment in a rat aortic allograft model of transplant arteriosclerosis (TA). METHODS: Aortic grafts were performed in Brown Norway (BN, donor) and Lewis (Lew, recipient) rats. The recipient rats were treated with LMWF (5 mg/kg/day) and sacrificed at 30 days. To determine the role of SDF-1 in mediating the effects of LMWF, a specific inhibitor of the SDF-1 receptor CXCR4, AMD 3100 (20 microg/kg/day), was used. The grafted segments were evaluated by morphometric (histochemical) analyses. RESULTS: Untreated aortic allografts exhibited severe intimal proliferation, indicative of TA. In contrast, LMWF treatment significantly prevented allograft intimal proliferation as compared with controls (5.7+/-3 vs. 66.2+/-6 microm, P<0.01) and permitted a normalization of the intima/media ratio (0.1+/-0.1 vs. 1.7+/-0.3, P<0.01). Further, LMWF treatment stimulated allograft reendothelialization, as evidenced by strong intimal endothelial nitric oxide synthase antibody and CD31 signals. Unexpectedly, AMD treatment failed to prevent the protective effect of LMWF on intimal thickening and AMD treatment alone was found to reduced intimal proliferation in allografts. CONCLUSIONS: We found that LMWF treatment reduced intimal thickness and induced the presence of an endothelial cell lining in the vascular graft at 30 days. Our findings may suggest a novel therapeutic strategy in the prevention of TA.     

Effect of cryopreservation on patency and histological changes of arterial isogeneic and allogeneic grafts in the rat model

Vascular grafting is used frequently in the management of length discrepancies between blood vessels. Cryopreservation permits vascular graft storage and aids availability; however, long-term patency of cryopreserved arterial allografts is not well established. Fifty Fisher and 55 Wistar rats were used in the study. Thirty-eight cryopreserved Fisher femoral arterial grafts were transplanted into the femoral arteries of 15 Fisher (cryoisografts) and 23 Wistar rats (cryoallografts). Thirty-two fresh Fisher arterial grafts were implanted into 32 Wistar femoral arteries (fresh allografts). The animals were killed at 1, 4, and 8 months in each group, and graft patency was assessed. One-month graft patency was 100% in all groups. At 4 months, graft patencies were 86%, 100%, and 75% in the cryoisografts, cryoallografts, and fresh allografts respectively. All cryoisografts and fresh allografts were patent, whereas all the cryoallografts were occluded at 8 months ( < 0.01). Cryopreserved rat arterial allografts offered satisfactory graft patency up to 4 months after implantation and may therefore be applicable clinically in selected cases.     

紫杉醇在大鼠原位肝移植中的作用及其对细胞毒性T淋巴细胞实验的影响

目的观察紫杉醇在大鼠原位肝移植中的作用及其对细胞毒性T淋巴细胞(CTL)的影响。方法建立Wistar→SD大鼠肝移植的急性排斥模型。将大鼠分为对照组(阻断全肝血流)、急排组(Wistar→SD肝移植)、紫杉醇组(Wistar→SD肝移植,紫杉醇腹腔注射0.75mg·kg-1·d-1,观察生存时间、病理改变、生化指标及CTL、T淋巴细胞凋亡情况。结果紫杉醇组大鼠的术后存活时间高于急排组,[(18.2±1.5)dvs(8.8±1.9)d,P0.01)。急排组的HE评分(Banff)高于紫杉醇组(7.80±0.83vs4.80±0.82,P0.01)。紫杉醇组的白蛋白水平高于急排组(P=0.003);紫杉醇组的谷丙转氨酶水平低于急排组(t=25.23,P0.01)。CTL检测中,急排组的特异性杀伤靶细胞的百分率均高于紫杉醇组(P0.01)。急排组的T淋巴细胞的凋亡率低于紫杉醇组[(7.16±1.56)%vs(16.47±2.51)%,P0.01]。结论紫杉醇在大鼠肝移植中具有免疫抑制作用,可能通过诱导T淋巴细胞凋亡来抑制T淋巴细胞的活化发挥作用。     

Immune Tolerance of Amniotic Fluid Stem Cell–Induced Rat Kidney Graft and Influences on Oxidative Stress

Objective

This study aimed to use amniotic fluid stem cells of donors to induce immune tolerance of heterogenous rat kidney graft for investigating the formation mechanism of immune tolerance.

Methods

With Wistar rats as donors and Sprague-Dawley (SD) rats as receptors, the heterogenous kidney graft animal model was established, and amniotic fluid stem cells of Wistar rats were isolated and cultured. Moreover, 40 SD rats were randomly divided into 4 groups. Creatinine (Cr), blood urea nitrogen (BUN), interleukin (IL) 2, interferon (IFN) γ, and oxidative stress levels in serum were detected, flow cytometry was used to detect changes of CD4 and CD8 cells, and quantitative changes of urinary protein and pathologic changes of transplanted kidney were observed.

Results

BUN, Cr, IL-2, IFN-γ, and oxidative stress levels and urinary protein quantity in rat serum of the test group were significantly lower than those of the control group, creatinine clearance rate was significantly higher than that of the control group, and renal pathologic injury extent was significantly milder than that of the control group.

Conclusions

Amniotic fluid stem cells can induce immune tolerance of rat kidney graft and inhibit oxidative stress level, improve kidney function, and alleviate kidney injury.     

Immunomodulation with intrathymic grafts or anti-lymphocyte serum promotes long-term intraspinal allograft survival

In this study, we sought to test whether introduction of fetal cells into the adult rat thymus would promote immunotolerance to subsequent donor-type allografts in the injured spinal cord. To first evaluate intrathymic survival of fetal central nervous system (CNS) tissue, fragments of E₁₄ Sprague-Dawley (SD) fetal spinal cord FSC_SD were injected into the thymuses of either adult, outbred SD, or Wistar rats. Histological examination revealed well-differentiated grafts in both the SD (10 out of 13) and Wistar (7 out of 13) recipients. We next examined whether prior intrathymic exposure to FSC graft-derived alloantigens leads to enhanced survival of subsequent allografts into the injured, adult spinal cord. Wistar rats thus first received FSC_SD tissue as intrathymic grafts coupled with single-dose, anti-lymphocyte serum (ALS) ablation of the circulating host T-cell population. Ten days later, FCS_SD was transplanted into an aspiration lesion of each intrathymic graft recipient's spinal cord. After 60 days, 87% of two-stage graft recipients (n = 15) exhibited viable intraspinal (IS) grafts compared to 38% (3 out of 8) observed in the controls (i.e., not receiving intrathymic grafts). Another group of Wistar rats that had received ALS (only) at the time of the IS FSC_SD transplant (n = 8) also had 75% graft survival rates after 60 days. These initial findings show that the intrathymic microenvironment can be a compatible ectopic site for fetal SC graft development and survival. Also, the enhanced survival of intraspinal grafts in animals with previous intrathymic implants or ALS administered at the time of grafting suggests the potential for inducing immunoprotection of some fetal neural allografts in adult recipients.     

紫杉醇抑制大鼠原位肝移植急性排斥反应的机制

目的 探讨紫杉醇抑制大鼠原位肝移植急性排斥反应的机制。方法 建立大鼠原位肝移植模型（Lewis-BN），将大鼠分为生理盐水对照组（A组），紫杉醇低剂量干预组（B组），高剂量干预组（C组）检测病理组织学改变，细胞免疫学指标。结果 紫杉醇明显延长术后生存（A组与B组，Log Rank=9．06，B组与C组，Log Rank=7．81，P均〈0．05），减轻肝脏病理组织学改变，降低外周血单核细胞特异的Th前体细胞的比率（t=8．9和11．8，P均〈0．05），促进脾CI）4^＋的淋巴细胞凋亡（T0=27．49和93．4，P均〈0．05），同时使Th1／Th2细胞平衡向Th2移动（t=4．93和5．92，P值均〈0．05）。结论 紫杉醇能够有效减轻肝移植大鼠的急性排斥反应，其机制可能与诱导活化的CD4^＋Th细胞凋亡，从而降低受体对供体细胞的反应，并促使Th1／Th2细胞平衡向Th2移动有关。