腺病毒介导FasL基因转染供肾对大鼠肾移植排斥反应的抑制作用

目的 以大鼠肾移植为载体,研究腺病毒Fas配体重组体(Ad-FasL)局部转染供肾对肾移植排斥反应的抑制作用.方法 供者为近交系Lewis大鼠,受者为近交系Wistar大鼠,建立大鼠的肾移植模型.实验分为3组,每组供、受者各8只.(1)Ad-FasL组:供者麻醉后,开腹,夹闭肾血管以下的腹主动脉、下腔静脉和肝门血管,经腹主动脉插管先向肾动脉内注入5 ml UW液,随后灌注9× 109 PFU/ml Ad-FasL液1 ml,灌注时间为3 min,取左肾作为供肾进行移植,取右肾检测Ad-FasL转染效率;(2)CsA组:受者肾移植术日至术后5 d采用CsA 5 mg/kg灌胃;(3)对照组:实验方法与Ad-FasL组相同,不同的是灌注液为AdV-5(Pfg140)空载体.术后比较各组的存活时间、移植肾组织学、肾功能和免疫组织化学等的改变.结果 Ad-FasL组受者平均存活时间为31.3 d,其中2例超过48 d;CsA组平均存活为16.5 d;对照组平均存活为9.1 d;Ad-FasL组与CsA组和对照组比较,差异均有统计学意义.Ad-FasL组的移植肾功能基本保持稳定,对照组在术后5 d切除对侧肾脏后血清肌酐浓度迅速上升;CsA组血清肌酐浓度呈现缓慢上升趋势.结论 Ad-FasL能成功转染大鼠供肾;转染Ad-FasL能使移植肾存活时间延长.Ad-FasL对淋巴细胞增殖具有明显的抑制作用,从而抑制了肾移植排斥反应.     

供者骨髓基质干细胞输注延长大鼠移植心存活时间的探讨

目的 探讨供者骨髓基质干细胞(MSC)输注在大鼠同种心脏移植术后的免疫调节及延长移植心存活时间的作用.方法 供者为近交系Wistar大鼠,受者为Fisher 344大鼠.处死供者后抽取其股骨和胫骨中骨髓,分离和培养MSC.通过混合淋巴细胞试验观察不同密度的MSC对异源性T淋巴细胞增殖反应的抑制作用.建立大鼠异位心脏移植模型,根据处理方式的不同,将受者分为MSC输注组和对照组,每组8只.Msc输注组:将含有2×106个MSC的林格氏液分别于术前1周、术中及术后连续3 d经尾静脉注入受者体内;对照组:用与MSC输注组相同的方法在相同时间点注入不含MSC的林格氏液.术后第5天,采用实时逆转录聚合酶链反应检测移植心组织中细胞因子的表达情况.结果 供者MSC可明显抑制异源性T淋巴细胞的增殖反应,且MsC密度越高抑制作用越强.MSC输注组Th1类细胞因子白细胞介素(IL)-1β和γ干扰素的表达要显著低于对照组;MSC输注组Th2类细胞冈子IL-4和IL-10呈高表达,而对照组基本不表达.MSC输注组移植心平均存活时间为(12.4±5.3)d,与对照组的(6.4±2.0)d比较,差异有统计学意义(P＜0.01).结论 输注供者MSC可通过改变Th1/Th2类细胞因子的平衡向Th2偏移诱导受者产生免疫调节作用,从而延长移植心存活时间.     

供者骨髓细胞骨髓腔内输注联合低剂量照射延长大鼠复合组织移植物存活时间

目的探讨供者骨髓细胞骨髓腔内输注联合低剂量照射对大鼠复合组织移植物的影响。方法以SD大鼠为供者,Wistar大鼠为受者,实验分4组进行:A组仅进行肢体移植;B组在肢体移植前1d,受者接受亚致死量60Co照射(4.5Gy/次,共2次,间隔4h),同时腹腔内注射氟达拉滨(50mg/kg);C组于肢体移植当天受者骨髓腔内输注供者骨髓细胞;D组在B组的基础上,受者于肢体移植当天骨髓腔内输注供者的骨髓细胞。所有受者术后均不用免疫抑制剂。术后观察移植物的存活情况及排斥反应征象,对D组存活超过120d的受鼠进行单向混合淋巴细胞反应以及SD大鼠、DA大鼠皮肤移植,同时通过组织学检查,了解受鼠的移植物抗宿主病(GVHD)情况。结果与其它实验组相比,D组移植物的存活时间显著延长(P<0.01),达(284.2±11.8)d,未见排斥反应征象,也未观察到GVHD,其它组均于术后近期发生排斥反应(<20d);D组大鼠对供者的淋巴细胞呈现低反应性,移植的供者同系大鼠的皮肤得以长期存活,而对第三方DA大鼠的淋巴细胞和皮肤呈现强烈的免疫反应。结论供者骨髓细胞骨髓腔内输注联合低剂量照射和短期氟达拉滨应用,在不用免疫抑制剂的情况下,能显著延长移植复合组织的存活时间。     

门静脉预输注供者凋亡骨髓细胞延长大鼠移植心脏的存活时间

目的探讨门静脉输注供者的凋亡骨髓细胞对大鼠移植心脏存活时间的影响。方法以Wistar大鼠为供者、SD大鼠为受者,将其随机分为4组,每组15只,A组为对照组,受者术前6d经门静脉输注RPMI1640培养基0.5ml,术后不注射环孢素A(CsA);B组为骨髓细胞输注组,受者术前6d经门静脉输注供者的骨髓细胞5×107个,术后不用CsA;C组为凋亡细胞输注组,受者术前6d经门静脉输注供者的凋亡骨髓细胞5×107个,术后不用CsA;D组为CsA组,受者术前3d起腹腔注射CsA5mg/kg,直至术后10d。60Coγ射线照射诱导骨髓细胞凋亡,各组大鼠建立腹部异位心脏移植模型。观察各组移植心的存活时间、组织病理学改变,测定受者血清中白细胞介素10(IL-10)及转化生长因子β1(TGF-β1)的含量及单向混合淋巴细胞培养(MLR)结果。结果C组移植心的存活时间为(14.00±0.95)d,较A组明显延长(P<0.01),但仍未达到长期存活(存活时间短于CsA组)。术后7d,C组移植心组织切片呈现中度急性排斥反应,心肌细胞损害不明显,但有大量淋巴细胞浸润。除术后7d的TGF-β1外,C组其它各测定时点的血清IL-10及TGF-β1均高于其它3个组。C组大鼠的脾细胞在供鼠脾细胞的刺激下,细胞增殖反应明显低于A组、B组(P<0.01),而对第三品系大鼠的脾细胞仍有较强的增殖反应,具有明显的抗原特异性;CsA组的细胞增殖均被抑制。结论门静脉预输注供者的凋亡骨髓细胞,可明显延长大鼠移植心脏的存活时间,但单纯单剂量的输注凋亡细胞并不足以建立长期、稳定的免疫耐受。     

苦杏仁苷对肾脏移植大鼠存活情况的影响

目的：研究苦杏仁苷（amygdalin）是否能增加肾移植大鼠的存活时间,及评估苦杏仁苷与环孢素（cyclosprin,CsA）联合用药时对大鼠肾移植的临床疗效。方法：20只肾移植大鼠随机分为4组：空白对照组、苦杏仁苷组、CsA组和苦杏仁苷＋CsA组,观察其存活时间及移植肾病理变化。结果：空白对照组存活时间最短（5.44±0.51）d,其与苦杏仁苷组（6.29±0.74）d比较具有统计学差异（P〈0.05）;苦杏仁苷＋环孢素组存活时间最长（11.84±0.76）d,其与环孢素组（9.26±0.74）d比较亦具有统计学差异（P〈0.05）,移植肾组织病理上各组均有不同程度的急性排斥反应,并具有各自的病理特点。结论：苦杏仁苷可在一定程度上延长肾移植大鼠的存活时间;苦杏仁苷和环孢素联合用药效果优于单用环孢素,其联合用药更能延长肾移植大鼠的存活时间。     

新型HLA衍生肽延长异基因大鼠移植肾存活时间

目的观察一种新型的人类白细胞抗原衍生肽(RDP1258)对大鼠肾移植后的免疫抑制作用。方法采用标准Fmoc法人工合成RDP1258。建立异基因大鼠原位肾移植模型。将已建立肾移植模型的大鼠随机分为4组,每组8只。A组:使用RDP1258 环孢素A(CsA);B组:单独使用RDP1258;C组:单独使用CsA;D组:不用任何药物。观察各组大鼠的存活时间,监测血清肌酐浓度,并进行移植肾彩色多普勒超声和常规病理检查。采用体外混合淋巴细胞反应(MLR)法检测长期存活大鼠的供者特异性免疫耐受状态。结果A、B、C和D组平均存活时间分别为(63.4±30.6)d、(18.3±7.3)d、(16.9±6.4)d和(9.4±2.6)d。A组与其他3组比较,差异有统计学意义。另外,混合淋巴细胞培养结果提示,长期存活的受者脾细胞对供者脾细胞的刺激不表现出明显细胞增殖反应,而对无关大鼠脾细胞仍能产生较明显的增殖反应。结论肾移植术后应用RDP1258结合小剂量CsA,能显著延长异基因大鼠移植肾存活时间,其机制可能与RDP1258诱导了受者对供者的特异性移植免疫耐受有关。     

小剂量环孢素A对大鼠同种异体肢体移植的免疫抑制作用

目的通过大鼠同种异体肢体移植模型,分析小剂量环孢素A(cyvlosporinA ,CsA)对大鼠同种异体肢体移植急性排斥反应的免疫抑制作用。方法采用雄性Wistar和SD大鼠为供、受体,以CsA为免疫抑制剂。对照组14只,将Wistar大鼠肢体移植至SD大鼠,术后不用药。实验组术后按用药剂量的不同分为2组( 2mg/kg组17只大鼠和CsA 6mg/kg组18只大鼠)。2组术后用药时间均为4周(每日1次共2周,然后每周2次共2周)。术后观察大鼠一般情况、移植肢体排斥反应及存活时间;用免疫荧光染色流式细胞仪检测各组手术前后T细胞亚群的变化。结果对照组移植肢体平均存活时间为[( 7.0 0±0 .78)d , x±s ,下同] ;CsA 2mg/kg组为( 3 7.18±0 .5 1)d ,CsA 6mg/kg组为( 3 3 .2 0±1.0 5 )d。术后第3天,对照组的CD4/CD8比值显著增高,移植肢体开始出现肿胀、皮肤红斑等表现。实验组的CD4/CD8较术前无明显变化。结论小剂量CsA能抑制大鼠同种异体肢体移植术后急性排斥反应的发生,并能延长移植肢体的存活时间。     

输注供者CD8+CD28-调节性T淋巴细胞抑制大鼠肝移植急性排斥反应的作用

目的 评价具有免疫抑制作用的CD8+CD28-调节性T淋巴细胞(Treg)体内输注在抑制大鼠肝移植急性排斥反应中的作用.方法 建立近交系大鼠肝移植自发耐受及急性排斥反应模型.从肝移植自发耐受模型受者脾脏中分离CD8+CD28-Treg,于急性排斥反应模型建立前1 d输注给受者,比较不同的输注组间受者的存活时间和移植肝病理学表现.结果 来自自发耐受模型(LEW大鼠为供者,DA大鼠为受者)的CD8+CD28-Treg输注可以延长急性排斥反应模型(LEW大鼠为供者,BN大鼠为受者)受者的存活时间,由(14.0±2.2)d延长至(24.0±3.0)d(P＜0.01),移植肝病理学显示排斥反应程度减轻.结论 大鼠肝移植自发耐受模型受者体内诱导的CD8+CD28-Treg具有抑制急性排斥反应的作用,该免疫抑制作用具有抗原特异性.     

环孢素A与他克莫司对大鼠原位小肠移植慢性排斥反应的影响

目的 建立稳定可靠的长期存活大鼠原位小肠移植慢性排斥反应(CR)模型,比较环孢素A(CsA)与他克莫司(Tac)诱导的CR的特点.方法 供、受鼠分别为雄性近交系F344、Lewis大鼠,移植小肠肠系膜上动脉、门静脉分别与受鼠肾下腹主动脉及下腔静脉端侧吻合,切除受鼠原小肠,移植小肠两端分别与受鼠肠行端端吻合.研究Ⅰ为受鼠手术当天至术后第13天肌肉注射CsA,5mg·kg-1 ·d-1.研究Ⅱ为手术当天至术后第13天及术后第20、27天肌肉注射Tac,低、中、高剂量组的剂量分别为0.3、0.5、1.0 mg·kg-1 ·d-1.观察大鼠存活率、体重及组织形态学改变.结果 研究Ⅰ中,受鼠术后60、90 d的病理表现均为CR,但肠黏膜钝化不明显.研究Ⅱ中,低、中剂量组受鼠最长存活126 d,而高剂量组受鼠存活超过180 d,体重增长曲线接近同系移植组.CsA与Tac制备的受鼠移植小肠病理学表现均为中、重度CR,但Tac制备的模型更接近临床小肠移植的CR病理学特征.结论 以F344大鼠为供鼠、Lewis大鼠为受鼠,分别以CsA、Tac为免疫抑制剂均可建立稳定的大鼠原位小肠移植CR模型,Tac制备的受鼠存活时间更长,病理学特征更为典型.     

灵长类动物预致敏后肾移植加速排斥反应模型的建立

目的 建立灵长类动物预致敏后肾移植加速排斥反应模型.方法 取血型相容的正常猕猴配对,预先将供者腹部全层皮肤移植到受者背部,使受者预致敏.2周后再将同一供者的左侧肾脏移植到受者腹腔内,间时切除受者自体双肾,术后予以环孢素A、霉酚酸酯和泼尼松治疗(致敏用药组),不用免疫抑制剂者为对照(致敏对照组),以未致敏的肾移植作为对照组.术后观察受者血肌酐变化、移植物存活时间及病理特点.结果 对照组的4只移植肾存活时间分别为9、18、8、7 d;致敏对照组的3只移植肾存活时间分别为3、3、4 d;致敏用药组的3只移植肾存活时间分别为2、3、4 d.移植皮肤于术后10 d出现排斥反应,至术后14 d被完全排斥.对照组于肾移植1周以后才发牛排斥反应,而致敏者均在肾移植后3 d左右发生较严重的排斥反应.结论 受者被供者皮肤预致敏后再行肾移植,可以加速移植物的排斥,且不能被环孢素A、霉酚酸酯及泼尼松所组成的三联免疫抑制方案逆转.     

Use of sphingosine-1-phosphate 1 receptor agonist, KRP-203, in combination with a subtherapeutic dose of cyclosporine A for rat renal transplantation

BACKGROUND: We demonstrate the long-term effectiveness of KRP-203 treatment in combination with a subtherapeutic dose of cyclosporine A (CsA) on rat renal allografts. METHODS: We tested the effect of KRP-203 in combination with CsA using a rat skin allograft model. The Pharmacokinetic interaction between CsA and KRP-203 was evaluated. The selectivity of KRP-203 for sphingosine-1-phosphate (S1P)1 and S1P3 receptors were investigated in vitro. Heart rate alteration following bolus injection of phosphorylated KRP-203 (KRP-203-P) or FTY720 (FTY720-P) was also monitored in rats. Finally, the long-term effectiveness of KRP-203 in conjunction with a low dose of CsA was investigated in a rat renal transplantation model. RESULTS: Administration of KRP-203 with CsA prolonged skin allograft survival. KRP-203 and CsA had no effect on the pharmacokinetics of the other. While FTY720-P activated both S1P1 and S1P3 receptors, KRP-203-P selectively activated S1P1, but not the S1P3 receptor (EC50:>1000 nM). Compared to FTY720-P, a tenfold higher dose of KRP-203-P was necessary to induce transient bradycardia. With a low dose of CsA (1 mg/kg/day), KRP-203 (0.3 mg/kg/day) significantly prolonged renal allograft survival (P<0.05, survival time: 9.8 days (CsA) vs. >27.4 days (CsA+KRP)). Although a higher dose of CsA (3 mg/kg/day) alone kept recipients alive, this caused severe renal graft dysfunction. Use of KRP-203 (3 mg/kg/day) in conjunction with CsA markedly improved graft function (P<0.05, creatinine clearance: 0.41+/-0.25 ml/min [CsA] vs. 1.15+/-0.16 ml/min [CsA+KRP]). CONCLUSIONS: The selectivity of KRP-203 for S1P1 reduces the risk of bradycardia, and the combination therapy of KRP-203 with CsA represents a safe and effective strategy for use in renal transplantation.     

The limited efficacy of cyclosporine in preventing rejection and graft-versus-host disease in orthotopic small bowel transplantation in rats

The effect of different schedules of cyclosporine treatment on the survival of small bowel allografts was studied in rats. The administration of a short course of CsA (15 mg/kg on days 0, 1, 2, 4, and 6) had no beneficial effect on graft-vs.-host disease and survival time of the recipient compared with untreated controls. CsA, 25 mg/kg for 1 or 2 weeks prolonged survival significantly (38.3 +/- 3.8 and 42.5 +/- 2.7 vs. 16.6 +/- 2.7, P less than 0.01). When combined with maintenance therapy, 15 mg/kg of CsA 3 times weekly until day 100, only 7 of 30 rats survived more than 100 days. In addition, GVHD was not consistently abrogated in these groups. Only high doses of CsA (25 mg/kg on days 0-6, 15 mg/kg on days 7-13, followed by maintenance therapy) could prevent the onset of GVHD, although the survival time of the transplants was not prolonged compared with untreated controls due to a toxic side effect of CsA on the transplants. It can be concluded that CsA used as monotherapy is ineffective in consistently ameliorating GVHD and rejection in the WAG-BN rat model. This model exhibits at least some of the immunological problems seen in large animal models and can be useful in studying combinations of immunosuppressive drugs or methods that may be applicable to small bowel transplantation in man.     

Enhancement of allograft survival by donor-specific transfusion one day prior to transplant. Importance of timing and specificity when DST is given with cyclosporine.

Donor-specific transfusion effects were studied in the ACI-to-Lewis rat heterotopic heart allograft model using cyclosporine immunosuppression. Low-dose CsA for 1 week plus a single fresh or stored DST given 1 day before allografting significantly prolonged graft survival over CsA therapy alone (median survival time 23.5 days vs. 10 days, P less than 0.01), but third-party transfusion did not (11.5 vs. 10 days, NS). When CsA was started at the time of DST and continued for 2 weeks, maximal graft enhancement was achieved after just one DST. DST/CsA was equally efficacious if given on any day before transplantation, provided CsA was started on the same day as the transfusion. However, pretransplant DST given without CsA shortened subsequent graft survival of day -1 DST/CsA treatment (14.5 days, n = 6, vs. 60 days for controls, n = 10; P less than 0.01). The addition of methylprednisolone to the DST/CsA protocol had no effect on graft survival (51 vs. 53 days, P = NS), but extending the period of postoperative CsA therapy for 4 weeks at reduced dose (2.5 mg/kg/day) significantly prolonged median survival (111 days, n = 11) and resulted in 45% permanent engraftment (greater than 120 days survival). CsA permits graft enhancement with a single DST as early as 1 day before grafting. This avoids the risk of sensitization from DSTs and can extend DST use to cadaveric graft recipients.     

术前自体骨髓间充质干细胞输注用于肾移植诱导治疗的临床研究

目的 观察骨髓间充质干细胞( BMSC)输注预防肾移植早期急性排斥反应(AR)的有效性和安全性.方法 88例肾移植受者分为BMSC组(43例)和对照组(45例),BMSC组于肾移植当天和术后2周时分别经外周静脉输注自体BMSC,对照组不进行任何诱导治疗.观察两组AR的发生情况、移植肾功能、并发症发生情况,随访时间为24个月.结果 两组患者基本资料的差异无统计学意义(P＞0.05).BMSC组在术后3、6个月AR的发生率分别为4.7％和9.3％,明显低于对照组的20.0％和26.7％(P＜0.05).BMSC组术后7、14和30d的估算肾小球滤过率(eGFR)分别为(1.28±0.62)、(1.33±0.63)和(1.47±0.49)ml/s,明显高于对照组(P＜0.01,P＜0.01,P＜0.05).BMSC组并发症的发生率为44.2％,低于对照组的66.7％(P＜0.05).两组24个月时AR的发生率和eGFR的差异无统计学意义(P＞0.05).两组移植后感染发生率的差异无统计学意义(P＞0.05).结论 术前自体BMSC输注可降低肾移植后早期AR的发生率,可促进移植肾功能早期恢复,安全性较好.     

A novel immunomodulator KRP-203 combined with cyclosporine prolonged graft survival and abrogated transplant vasculopathy in rat heart allografts

To find more effective and less toxic immunosuppressive strategies in long-term treatment for organ transplantation patients, we examined the effects on rat heart allograft survival of a novel sphigosine-1-phosphate receptor agonist, KRP-203, combined with a subtherapeutic dose of cyclosporine (CsA). Rat heart transplantation was performed across a major histocompatibility complex-incompatible (DA to LEW) rat combination. KRP-203 alone showed little or no effect on heart allograft survival. In contrast, KRP-203 combined with a subtherapeutic dose of CsA led to prolonged allograft survival. Histologic analyses showed that the combination completely suppressed acute rejection, as characterized by allograft vasculopathy, mononuclear cell infiltration, and myocardial necrosis in the heart allografts. RT-PCR analysis showed that the allografts treated with CsA or KRP-203 alone showed no suppression of IL-10, IFN-gamma, and TNF-alpha mRNA expression, but when combined with a subtherapeutic dose of CsA it completely suppressed their mRNA expressions. Furthermore, the combination treatment reduced donor-specific antibody production. KRP-203 combined with a subtherapeutic dose of CsA synergistically prolonged rat heart allograft survival. The combination of CsA with KRP-203 may provide an option to prevent allograft rejection and reduce adverse effects.     

延迟性异种移植排斥反应的病理特征及IgG的作用

目的利用小鼠→大鼠心脏移植模型，探讨延迟性异种移植排斥反应(DXR)的病理特征及IgG的作用。方法将移植大鼠随机分成4组对照组(A组，n＝6)；环孢素A(CsA)组(B组，n＝6)，CsA每2日用药1次，每次20mg/kg，自移植当日(day0)起使用；环磷酰胺(CyP)组(C组，n＝6)，移植前1d给予CyP40mg/kg，自移植后第1天起每2日用药1次，每次20mg/kg；CsA加CyP组(D组，n=5)。血清IgG水平用ELISA法测定；C     

A randomized prospective trial comparing cyclosporine monotherapy with triple-drug therapy in renal transplantation

In a prospective trial 151 recipients of renal transplants were randomly assigned to treatment with CsA alone (74 patients) and to low dose of AZA, prednisolone, and CsA (77 patients). At two years, graft survival was 84% for the monotherapy and 90% for the triple therapy. This difference was not statistically significant. The number of rejection episodes was similar in the two groups, but the severity of rejection was significantly worse among the patients on monotherapy. More kidneys were lost because of rejection (6 versus 3), and a higher number of methylprednisolone pulses was used for treating rejection (5.2 +/- 2.3 versus 4.3 +/- 2.9; P = 0.0077). CsA nephrotoxicity episodes were more frequent among patients on monotherapy (23 versus 7; P less than 0.02). Infectious episodes were equally distributed between the two groups. Creatinine clearance was poorer in the monotherapy-treated patients at the third month (42 +/- 16 ml/min versus 48 +/- 15 ml/min; P = 0.02), but no differences were observed between the two groups since the sixth month after transplantation. Many patients on monotherapy required changes in maintenance therapy. In fact, one patient was switched to conventional immunosuppression because of Cremophor-induced anaphylaxis. Another patient who developed Kaposi's sarcoma 4 months after surgery was switched to steroids alone. Excluding 5 patients who lost their grafts a few days after transplantation, only 30 of 74 patients (40%) could be kept without steroids. We conclude that both the therapeutic protocols can give good results in renal allotransplantation; however, monotherapy could create some problems in keeping the balance between drug toxicity and significant immunosuppression. On the contrary, triple therapy is easier to handle, especially in the early posttransplant period when the differential diagnosis between acute rejection and CsA-related nephrotoxicity can be difficult even for a skilled clinician.     

肝再生增强因子对大鼠腹腔移植的肝细胞的影响

目的 探讨肝再生增强因子(ALR)对急性肝功能衰竭大鼠腹腔移植的肝细胞的影响.方法 采用D-氨基半乳糖诱导SD大鼠急性肝功能衰竭(AHF),然后将其随机分为空白对照组(仅接受生理盐水腹腔注射)、移植对照组(腹腔移植SD大鼠的肝细胞2×107个)、环孢素A组(CsA组,接受肝细胞移植后腹腔注射CsA 6 d)、ALR组(接受肝细胞移植后腹腔注射ALR 6 d)和ALR对照组(仅腹腔注射ALR 6 d).实验期为14 d,观察受者的存活情况及移植肝细胞存活情况,检测腹腔内细胞CD4、CD8及CD68的表达情况,测定血清及腹腔冲洗液中自细胞介素1β(IL-1β)和肿瘤坏死因子a(TNF-a)的水平.结果 空白对照组、移植对照组、CsA组、ALR组及ALR对照组的受者2周存活率分别为0、46.7%、20%、66.7%和14.3%,ALR组显著高于空白对照组(P=0.001).移植后1～2 d,ALR组血清TNF-a和IL-1β明显低于空白对照组和移植对照组(P<0.01);移植对照组腹腔冲洗液中TNF-a和IL-1β水平明显高于其它各组(P<0.05,P<0.01).至移植后14 d,各组存活大鼠的血清TNF-a和IL-1β水平接近正常水平.移植后1～2 d,ALR组移植物内CD68表达水平为(0.5±0.3)%,明显低于移植对照组和CsA组(P<0.01);ALR组腹腔内细胞CD68、CD4及CD8表达水平分别为(1.3±1.2)%、(0.1±0.3)%和(0.2±0.1)%,均明显低于移植对照组(P<0.01,P<0.01,P<0.05).移植后1～3 d,接受肝细胞移植的大鼠腹腔内可见聚集成团的肝细胞结节,ALR组存活的肝细胞数明显多于移植对照组和CsA组,且炎症细胞浸润较少,至移植后14 d,仅ALR组可见少量形态正常的肝细胞.结论 腹腔内肝细胞移植联合ALR腹腔注射能提高AHF大鼠的存活率;ALR能短期改善移植肝细胞的存活状况.