The production and clearance of endothelin and its influence on kidney function after liver transplantation in rats

To assess the involvement of endothelin-1 (ET-1) in rat liver allograft rejection, we evaluated ET-1 expression in tissues obtained from BN (RT1ⁿ) to BN rats (group 1), and DA (RT1^a) to BN rats (group 2). The ET-1 levels in group 1, determined by radioimmunoassay, remained low in the serum, liver, and bile, but in group 2, they peaked on postoperative day (POD) 5 in the liver, kidney, bile, and urine, at 344 ±31.6pg/gwet, 306 ± 97.4pg/gwet, 1008 ± 258 pg/day, and 156 ± 45 pg/day, respectively, whereas levels in the serum peaked on POD 7 at 38.7 ± 13.1 pg/ml. In the portal vein (PV) ET-1 showed extremely high levels without statistical difference between groups 1 and 2, at 93.0 ± 15.5, and 83.0 ± 9.84 pg/ml on POD 7, respectively. However, in the suprahepatic vena cava (SHVC) and the abdominal aorta (AO), the ET-1 levels were statistically higher in group 2 compared to group 1 (P < 0.01). Immunohistochemical staining showed decreased staining of the liver and kidney in group 2 on POD 7. In conclusion, increasing levels of ET-1 were released from the liver and kidney during the early stage of rejection, resulting in the high ET-1 levels in these tissues, which were cleared promptly. However, an increased production of ET-1 was not observed in association with the release of ET-1.     

Involvement of endothelin in graft-versus-host disease after rat small bowel transplantation

Endothelin (ET-1) expression was evaluated by radioimmunoassay in both plasma and various tissue specimens serially obtained from LBN-F1 recipients of LEW heterotopic small bowel allografts. The recipients showed graft-versus-host disease (GVHD), which histologically became apparent on postoperative day (POD) 13. The ET-1 levels peaked on POD 9 in the kidney, lung, and host intestine at 51.0 ± 21.1, 90.9 ± 59.6, and 25.4 ± 11.8 pg/g wet, respectively, and peaked on POD 11 in the plasma at 7.7 ± 3.2 pg/ml; thereafter, they decreased to basal levels in both the plasma and tissue specimens on POD 13. An immunohistochemical study of these organs showed a corresponding increase in ET-1 staining in both the endothelial and epithelial cells on PODs 5 and 9, and a reduction in staining on POD 13. In conclusion, ET-1 was found to be increasingly released from the target cells of GVHD before any histological changes became apparent, thus suggesting the pathophysiological involvement of ET-1 in intestinal GVHD. Received: 11 June 1996 Received after revision: 3 September 1996 Accepted: 28 October 1996     

Changes in blood ketone body ratio with reference to graft viability after liver transplantation in rats

Arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate; KBR), which reflects hepatic mitochondrial redox potential, was measured during a 2-week period after orthotopic liver transplantation in three groups of rats: group 1, the isogenic combination of LEW (RT1¹) graft to LEW recipient as control; group 2, the allogenic combination of ACI (RT1^a) graft to LEW recipient without immunosuppressive treatment; and group 3, the allogenic combination of ACI to LEW with immunosuppressive treatment using cyclosporin (CyA). Isogenic recipients survived indefinitely. Allogenic recipients in group 2 had severe rejection with a mean survival of 10.3±0.54 days, while 77.8% of the allogenic recipients in group 3 survived more than 30 days. KBR of rats surviving more than 2 weeks in groups 1 and 3 gradually increased post-transplantation and was maintained at a high level. By contrast, though KBR in group 2 was restored at 3 days, it gradually fell and remained at a significantly low level (P<0.001). It is suggested that KBR provides an accurate indicator for evaluating metabolic viability of the critically deteriorating liver graft accompanied by severe rejection.     

Changes in blood ketone body ratio with reference to graft viability after liver transplantation in rats

Abstract. Arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate; KBR), which reflects hepatic mitochondria] redox potential, was measured during a 2-week period after orthotopic liver transplantation in three groups of rats: group 1, the isogenic combination of LEW (RT1^l) graft to LEW recipient as control; group 2, the allogenic combination of ACI (RT1^a) graft to LEW recipient without immunosuppressive treatment; and group 3, the allogenic combination of ACI to LEW with immunosuppressive treatment using cyclosporin (CyA). Isogenic recipients survived indefinitely. Allogenic recipients in group 2 had severe rejection with a mean survival of 10. 3 ± 0. 54 days, while 77. 8% of the allogenic recipients in group 3 survived more than 30 days. KBR of rats surviving more than 2 weeks in groups 1 and 3 gradually increased post-transplantation and was maintained at a high level. By contrast, though KBR in group 2 was restored at 3 days, it gradually fell and remained at a significantly low level ( P < 0. 001). It is suggested that KBR provides an accurate indicator for evaluating metabolic viability of the critically deteriorating liver graft accompanied by severe rejection.     

The characterization of reconstituted passenger leukocytes on the induction of tolerance in rat liver transplantation

The tolerance induced by orthotopic liver transplantation [DA (RT1^a) rats to PVG (RT1^c) rats] can be prevented by total body irradiation of the donor rat. Reconstitution of the irradiated donor with DA splenic leukocytes reintroduces this tolerance. To investigate the major histocompatibility complex (MHC) specificity of passenger leukocytes, irradiated DA donors were reconstituted by third-party BN (RT1ⁿ) splenic leukocytes. The reconstitution with BN splenocytes re-established DA-specific tolerance in PVG recipients, as confirmed by subsequent DA cardiac allografting, while BN hearts were rejected with second-set tempo. To determine which cell components play an important role in re-establishing liver graft tolerance, DA splenic leukocytes were further purified into three types: T, B, and adherent cells. Only “T-cell-enriched” preparations restored liver graft tolerance in three out of five PVG recipients. These results suggest that passenger leukocytes of differing MHC types can help to induce liver-specific tolerance and that T cells in the liver graft may be essential to regulate tolerance induction. Received: 31 December 1996 Received after revision: 14 April 1997 Accepted: 15 April 1997     

Host immune suppression after small bowel/liver transplantation in rats

Simultaneous liver grafting in the Lewis (RT1¹)-to-DA (RT1^a) rat strain combination protects small intestinal grafts from rejection. The present study examined host immune responses after combined small bowel/liver transplantation (SBL) in this model. Orthotopic liver transplantation and heterotopic small intestinal transplantation were performed simultaneously and compared with isolated small bowel allografts (SBA) and isolated small bowel isografts (SBI). All rats were sacrificed on postoperative day (POD) 7 or 14 for immunological and histological studies. The mean time to rejection of the SBA was 6.6±0.3 days. Incontrast, there was no clinical or histological evidence of intestinal rejection in SBL recipients during the 14 days of follow-up. The SBL recipients showed clinical and histological evidence of graft-versushost disease (GVHD). Lmphocyte proliferation and IL-2 production in response to donor antigens were suppressed after SBL transplantation compared with the SBA or the SBI controls (P<0.05). Cell-mediated cytotoxicity and lymphocytotoxic antibody production against donor cells were also significantly inhibited in the SBL recipients compared with the SBA control group (P<0.05). We conclude that SBL transplantation in the Lewis-toDA rat strain combination: (1) suppresses host alloimmune responses, (2) prevents early intestinal rejection, and (3) favors the development of GVHD.     

Evidence that both cyclosporin and azathioprine prevent warm ischemia reperfusion injury to the rat liver

The present work was undertaken to study whether the immunosuppressive agents cyclosporin (CyA) and azathioprine (AZA) ameliorate hepatic injury after warm ischemia. A temporary, normothermic liver ischemia was induced in female Sprague-Dawley rats. The rats were treated with CyA (10 mg/kg per day p.o.), AZA (8 mg/kg per day p.o.), or vehicles for 4 days before surgery. Seven-day survival rates after 60 min of ischemia improved significantly with CyA (76.2%, P<0.005) and AZA (78.6%, P<0.001) treatment, compared with 43.0% for the control group. The highest levels of serum aminotransferases in the treatment groups tended to be lower than those in the control group. The peak values for the percentage of liver necrosis, an indicator of the extent of hepatic necrosis, in the animals treated with CyA (26.1%±7.2%, mean±SEM) and AZA (32.1%±5.7%) were significantly lower than in the control group (47.4%±3.7%). Lipid peroxidative damage after reperfusion, assessed as the hepatic malondialdehyde (MDA) concentration, was significantly suppressed by pretreatment with CyA and AZA. Histological findings coincided with other parameters. This study demonstrates that both AZA and CyA have beneficial effects on normothermic liver ischemia in rats. It is suggested that the diminished lipid peroxidative damage with these agents might be one of the mechanisms responsible for this.     

Endotoxin in the peripheral blood during acute intestinal allograft rejection

Intestinal rejection is associated with increased gut permeability and bacterial translocation. The present study examined endotoxin and proinflammatory cytokines in the peripheral circulation during acute intestinal rejection. Heterotopic intestinal transplants were performed using Lewis rats (RT1¹) as donors and DA rats (RT1^a) as recipients. DA rats with intestinal isografts were used as controls. Serum samples were obtained at sacrifice on postoperative days (POD) 7 and 14. Lipopolysaccharide (LPS) was measured using the limulus amoebocyte lysate assay. Interleukin-1 (IL-1) and 6 (IL-6) and tumor necrosis factor- (TNF-) were measured using bioassays. Large amounts of LPS were detected in the serum of intestinal allograft recipients concurrent with the development of graft rejection. Serum IL-6 and TNF- levels were significantly elevated in the allograft recipients on both POD 7 and 14 when compared to DA isografts (P<0.05). Serum IL-1 activity was not detected in the allograft or isograft recipients at either of the two time points. Further studies are warranted to determine the role of intraluminal bacteria and their products in the pathophysiology of intestinal allograft rejection.     

Clinical pharmacokinetics of Neoral in pediatric recipients of primary liver transplants

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i. v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22 % and 21 % for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability. Received: 29 November 1996 Received after revision: 10 April 1997 Accepted: 15 May 1997     

Endothelin-1 plasma levels and hypertension in cyclosporine-treated renal transplant patients

Experimental models suggest that endothelin-1 (ET-1) has a significant role in the pathogenesis of cyclosporin A (CyA)-induced hypertension. However, its serum levels evaluated in different studies, including patients who received solid organ transplants, exhibited controversial results. Our study population consisted of 43 renal transplant patients: 33 were taking CyA as a component of their immunosuppressive regimen (CyA group) and 10 that were not taking CyA (control group). Baseline laboratory data, blood pressure and ET-1 levels were taken at baseline and 3 and 4 h after the ingestion of CyA. In the control group samples were collected in the corresponding periods of time. Blood pressure was significantly higher in the CyA group (mean blood pressure: 101.2 +/- 9.5 vs. 91.1 +/- 10.7 mmHg; p < 0.001), who also presented higher serum creatinine (1.2 +/- 0.28 vs. 0.97 +/- 0.13 mg/dL; p < 0.001) and ET-1 levels. In the CyA group an ET-1 peak was evident by the third hour after CyA ingestion that showed its maximum concentration after 1-2 h; the control group exhibited significantly lower levels of ET-1 (p = 0.044). ET-1 levels compared between patients with and without hypertension showed a non-statistically significant difference (1.54 +/- 0.76 vs. 1.27 +/- 0.62 ng/mL; p = 0.27, respectively). In conclusion, in the present study chronic CyA ingestion was associated with higher blood pressure and plasma ET-1 levels.     

内皮素-1单克隆抗体对肝移植缺血再灌注损伤保护作用的实验研究

目的: 探讨内皮素-1(ET-1)抗体对移植肝缺血再灌注损伤的保护作用.方法: 选用雄性SD大鼠108只,分为对照组、肝移植组与ET-1抗体组,观察应用抗ET-1单抗前后移植肝热缺血15 min,冷缺血40 min再灌注后第4小时血浆ET-1、丙氨酸转移酶(ALT)、透明质酸(HA)以及肝组织中ET-1和丙二醛(MDA)含量及肝组织病理学变化;同时,在移植肝再灌注后的第1,4,12,24小时观察ET-1的变化规律.结果: 移植肝缺血再灌注后,血浆和肝组织中ET-1,血浆HA,ALT和肝组织中MDA显著升高,而ET-1抗体组血浆和肝组织中ET-1,血浆HA,ALT和肝组织中MDA与肝移植组相比显著降低(P<0.01,P<0.05 ),且肝组织的淤血程度和损伤程度显著改善.结论: ET-1单克隆抗体对移植肝缺血再灌注损伤有保护作用.     

Systemic liberation of interleukin-8 in the perioperative phase of liver transplantation

Serum levels of interleukin-8 (IL-8) were investigated in the perioperative phase of liver transplantation (LTx) in order to help determine whether this cytokine might serve as a parameter for preservation injury. In a study of 45 patients undergoing LTx, systemic IL-8 was estimated at the end of the anhepatic phase, at 30, 60, and 120 min after reperfusion of the graft, and 24 h and 7 days after LTx. A maximum mean concentration of 665 ± 135 pg/ml was seen 60 min after LTx. The minimum was found on the 1st postoperative day (POD 1): 328 ± 33 pg/ml. Significant changes were found between 60 min and PODs 1 and 7, as well as between 120 min and POD 1. Differences in cold ischemia time were not found to be significant. We conclude that monitoring of systemic IL-8 levels is not useful in the development of new liver preservation concepts. Received: 12 September 1996 Received after revision: 27 February 1997 Accepted: 3 March 1997     

A rat model of monitoring liver allograft rejection

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection. Received: 2 July 1996 Accepted: 28 October 1996     

Restoration of tolerance to rat hepatic allografts by spleen-derived passenger leukocytes

The tolerance induced by orthotopic liver transplantation (OLT) in certain combinations of rat strains can be prevented by total body irradiation (TBI) of the donor. We demonstrate here that the intravenous inoculation of splenic leukocytes into irradiated donors before OLT could re-establish tolerance in association with a state of microchimerism detected in the recipients. When donor DA (RT1^a) strain rats were irradiated with 1000 rad 24 h before liver harvesting and subsequent liver implantation into PVG recipients, five out of six rats died from rejection in this normally tolerogenic OLT (DA-PVG) combination. Injection of 1.5x10⁸ splenic leukocytes from naive DA rats into the irradiated DA donor rats 24 h before OLT restored the tolerogenic potential of the liver allografts. Immunofluorescence assay revealed an increased number of donor (DA) type cells in the PVG recipient bearing a repopulated DA liver, compared to the PVG recipient of an irradiated liver. These results suggest that passenger leukocytes reconstituted by splenic leukocytes have the capacity to protect liver allografts.     

rhALR在大鼠部分肝移植术后肝再生中的作用及其机制研究

目的 探讨大鼠部分肝移植术后腹腔注射重组人肝再生增强因子(recombinant human augmenter ofliver regeneration,rhALR)促进肝移植术后肝细胞再生的作用及其机制.方法 建立大鼠原位60% 肝脏移植模型,部分肝移植术后腹腔注射rhALR 40 μg/kg 2 次/d(实验组,对照组注射等体积的注射用水);取术后第1、2、3、5、7 天大鼠血清及肝组织,检测血清谷丙转氨酶(ALT),测定肝细胞PCNA LI 的变化,RT-PCR 检测肝组织IL-6 mRNA Cyclin-D1 mRNA 的表达.结果 实验组(A 组)与对照组(B 组)比较,术后第1、2 天A 组血清ALT 显著低于B 组.A 组术后第1、2、3、5 天的PCNA LI 均明显高于B 组同一时点的PCNA LI(P<0.05).A 组术后第2 天的肝细胞AI 明显低于B 组同一时点的肝细胞AI(P<0.05);A 组术后肝组织IL-6 mRNA 的表达与B 组在各观察时点间比较均无统计学差异(P>0.05);A 组术后第1 天肝组织Cyclin D1 mRNA 的表达明显高于B 组同时点的表达(P<0.05),其余观察时点无明显差异.结论 大鼠部分肝移植术后应用rhALR 可以明显促进肝细胞的再生,降低血清ALT,稳定肝细胞膜,保护肝细胞功能.rhALR 促进大鼠部分肝移植术后的肝再生可能并不是通过上调启动阶段重要因子IL-6 mRNA 的表达发挥作用,而是通过上调增殖阶段重要因子CyclinD1mRNA 的表达发挥作用.     

Adenovirus-mediated gene transfer using in-situ perfusion of the liver graft

To establish an efficient technique for adenovirus-mediated gene transfer in liver transplantation, we evaluated the in situ perfusion of liver grafts. The grafts were perfused in situ with 1 × 10¹⁰ of E1-deleted, replication-defective adenoviral vectors encoding the LacZ gene driven by the human CMV promoter, either through the hepatic artery (group 1) or the portal vein (group 2). Group 3 animals served as negative controls; their liver grafts were perfused with lactated Ringer's solution through the portal vein. PCR confirmed the presence of viral DNA in every graft perfused with viral vectors. In X-gal staining, positive staining was observed almost exclusively at the portal triad in group 1, whereas in group 2 minimal staining was observed, predominantly in the parenchymal area. Protein production from the transfected gene was confirmed by a functional protein assay; the values were 0.16 % ± 0.07 % liver protein in group 1, 0.13 % ± 0.02 % in group 2, and 0.007 % ± 0.0003 % in group 3 on postoperative day 2. In conclusion, in situ perfusion of the viral vectors through the hepatic artery resulted in an effective expression of the transfected gene, predominantly at the portal triad. Received: 15 July 1996 Received after revision: 1 November 1996 Accepted: 12 November 1996     

Amelioration of tumor necrosis factor release by cyclosporine in warm ischemia/reperfusion injury of the rat liver: with special reference to hepatic ultrastructure

Mechanisms by which an immunosuppressant (cyclosporine, CsA) ameliorates warm ischemic injury of the liver were studied. Female Sprague-Dawley rats were subjected to 60-min normothermic liver ischemia. Animals were assigned to one of two groups: group I, controls with vehicle treatment; group II, treatment with CsA (10 mg/kg). CsA was given orally for 4 consecutive days prior to the induction of hepatic ischemia. In addition to a survival study, plasma levels of endotoxin, serum activity of tumor necrosis factor-α (TNF), and serum levels of aminotransferases were measured in blood samples collected from the suprahepatic vena cava, and hepatic ultrastructural alterations were examined under an electron microscope. The 7-day survival rate was significantly higher in the CsA-treated animals. In the control group, serum TNF levels were elevated following reperfusion and peaked at 3 h. When the values at 3 h post reflow were compared, the animals given CsA had significantly lower levels of TNF (170.0 ± 30.5 pg/ml for group I, 67.6 ± 13.7 for group II, mean ± SEM; P < 0.05). The sinusoidal lining cells and hepatocytes were drastically destroyed at 6 h post reflow in the control group, although the degree of injury at 1–3 h was less severe. On the other hand, the endothelium and parenchymal liver cells in the CsA-treated group were well preserved at 6 h in comparison with those in the control group. Our data suggest that modulation of TNF production is one of the mechanisms through which CsA prevents the exacerbation of ischemia/reperfusion injury of the liver. Received for publication on Aug. 12, 1998; accepted on Feb. 2, 1999     

Liver allograft rejection in rats depleted of CD8+ cells

The mechanism(s) of rejection or tolerance induction is a competitive, complex process that presumably involves interactions between multiple subpopulations of T lymphocytes. We investigated the roles of CD8⁺ cytolytic and CD4+ helper T cells in rat strains that tolerate liver allografts and that differ at both the major histocompatibility complex (MHC) (RT1) and minor histocompatibility genes. Orthotopic liver transplantation (OLT) with arterial reconstruction was performed with Brown Norway (BN) (RT1ⁿ) donors and Lewis (RT1¹) recipients, some of which were untreated, others treated with anti-CD8 antibody, and still others treated with anti-CD4 antibody. Liver graft rejection was monitored for 28 days on the basis of two criteria: (1) serum levels of AST enzyme at 3-day intervals and (2) liver biopsies at weekly intervals and at the time of sacrifice at the end of the study period. In the untreated control group, an elevation of AST was found to peak at day 6 after grafting, and it remained elevated until day 28 (AST 542±72 U/l). Histologically, signs of severe rejection were first observed on day 9; these changed to moderate rejection about day 21 and to mild rejection by day 28, when the animals were sacrificed. Recipients pre-treated with anti-CD8 demonstrated a significant elevation of AST within 6 days that, unlike in the control recipients, continued to rise sharply through the observation period (AST 1127±181 U/1, P=0.009 vs control group). Liver biopsies showed mild rejection at day 9 and moderate rejection at days 21 through 28. Recipients pretreated with anti-CD4 showed a time course of enzyme elevation and severity of rejection that was not significantly different from that observed in the control group. However, anti-CD4 treatment resulted in only 75% depletion of CD4⁺ cells in peripheral blood as compared to complete elimination of CD8⁺ cells following anti-CD8 treatment. Functional studies of spleen and liver-infiltrating lymphocytes obtained after 28 days showed low proliferative response in mixed lymphocyte culture with both BN and PVG stimulator spleen and lymph node cells. These results suggest that in this donor/recipient combination, removal of CD8⁺ cells increases the severity of rejection as demonstrated by a progressive rise in AST and histology. Moreover, OLT in this combination results in a profound, nonspecific inhibition of proliferative T-cell responses to MHC alloantigens.     

大鼠肝移植排斥反应时γ干扰素及白细胞介素10的表达及意义

目的 探讨大鼠肝移植排斥反应时γ干扰素(IFN-γ)及白细胞介素10(IL-10)的表达及意义.方法 采用改良的Kamada"二袖套法"制备大鼠原位肝移植模型,同系移植组供、受者均为SD大鼠;同种异体移植组的供者为Wistar大鼠,受者为SD大鼠;另设假手术组.术后7 d处死动物,观察移植肝脏的组织学变化,检测血清IFN-γ和IL-10的含量,以及移植肝脏内IFN-γ和IL-10 mRNA的表达.结果 同种异体移植组移植肝脏有较多坏死肝细胞,汇管区及中央静脉周围可见以淋巴细胞为主的炎症细胞浸润,胆管上皮细胞可见胞浆空泡变性、核固缩或碎裂,整个肝小叶结构紊乱.同系移植组肝脏组织结构仅有轻度缺血再灌注损伤表现,汇管区有较少炎症细胞浸润,胆管上皮细胞结构和肝小叶结构基本正常.同种异体移植组血清IFN-γ为(386.7±14.4)Pg/ml,明显高于同系移植组的(159.8±16.5)pg/ml(P<0.05);同种异体移植组血清IL-10为(126.3±13.1)pg/ml,明显低于同系移植组的(288.3±17.1)pg/ml(P<0.05).同种异体移植组移植肝组织内IF-γ mRNA表达水平明显高于同系移植组(P<0.05),而IL-10 rnRNA表达水平明显低于同系移植组(P<0.05).结论 大鼠肝移植排斥反应时IFN-γ表达明显升高,IL-10表达明显降低;T_H1/T_H2型细胞因子的动态平衡可能在大鼠肝移植排斥反应中起着重要作用.