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。     

西罗莫司对人肝癌裸鼠肝脏移植瘤生长的影响

Objective To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice. Methods HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus (FK506). The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected by immunohistology, microvessel density (MVD) was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynuclcotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Results The tumor weight was (352±38) mg, (683±53) mg and (675±45) mg in SRL, FKS06 and control group respectively. The tumor weight was significantly decreased in SRL group (P < 0.0 I), and there was no difference between FKS06 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group (P < 0.05), and it was not significantly different between FK506 group and control group (P > 0.05). Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group (P < 0.01). Conclusion SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.     

西罗莫司对人肝癌裸鼠肝脏移植瘤生长的影响

Objective To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice. Methods HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus (FK506). The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected by immunohistology, microvessel density (MVD) was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynuclcotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Results The tumor weight was (352±38) mg, (683±53) mg and (675±45) mg in SRL, FKS06 and control group respectively. The tumor weight was significantly decreased in SRL group (P < 0.0 I), and there was no difference between FKS06 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group (P < 0.05), and it was not significantly different between FK506 group and control group (P > 0.05). Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group (P < 0.01). Conclusion SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.     

嗜酸性粒细胞升高在诊断肝移植术后迟发性急性排斥反应中的价值

目的 评价外周血嗜酸性粒细胞升高诊断肝移植6个月后发生的急性排斥反应(acute rejection,AR)的价值.方法 回顾性分析肝移植术后肝穿刺活检患者的临床资料,根据病理确诊结果分为AR组和非AR组,比较2组患者肝穿刺当天或前1天血常规中白细胞的分类,比较嗜酸性粒细胞升高在早期(术后1个月内)、中期(1～6个月)和后期(6个月后)AR组中的发生率,并评价嗜酸性粒细胞升高诊断后期AR的敏感性和特异性.结果 共185例次肝穿刺、161例肝移植患者资料入组,110例次AR,其中早期32例(29.1％)、中期54例(49.1％)、后期24例(21.8％).AR组白细胞总数、中性粒细胞绝对值和相对值显著低于非AR组,但淋巴细胞相对值、嗜酸性粒细胞绝对值和相对值显著高于非AR组.嗜酸性粒细胞绝对值≥0.4×109/L或相对值≥4％共28例,其中AR组25例(22.7％),早期、中期和后期AR分别为2例(6.3％)、13例(24.1％)和10例(41.7％),嗜酸性粒细胞升高诊断后期AR的敏感性和特异性分别为41.7％和100％.结论 肝移植术后急性排斥反应患者嗜酸性粒细胞显著高于非排斥患者,嗜酸性粒细胞升高对肝移植术后迟发性急性排斥反应具有很高的诊断价值.     

抗CD40L单克隆抗体在异种胰岛移植排斥反应中的作用

目的 探讨抗CD40L单克隆抗体在异种胰岛移植排斥反应中的作用及其机理.方法 建立人-大鼠异种胰岛移植模型,用抗CD40L单克隆抗体进行干预治疗,观察糖尿病大鼠行异种胰岛移植后的血糖变化,糖尿病大鼠和移植物的生存情况及移植物病理形态学改变,采用 ELISA法检测糖尿病大鼠细胞因子IL-2和TNF-α水平的变化.结果 ①全部糖尿病大鼠在胰岛移植后第(2.3±0.2) d血糖降至正常,对照组血糖在移植后第(8.1±0.6) d开始明显升高,治疗组血糖在移植后第(18.5±1.2) d开始明显升高,明显晚于对照组(P＜0.01).②治疗组移植物存活时间[(22±8.2) d]较对照组[(10±2.1) d]显著延长(P＜0.01).③糖尿病大鼠生存时间,治疗组[(35±6.5) d]显著长于对照组[(21±5.7) d ],P＜0.05.④对照组在移植后第(3.2±0.3) d IL-2及TNF-α的水平均急剧上升,至移植后第(7.3±0.5) d达到高峰; 治疗组IL-2及TNF-α的水平在移植后第(22.6±1.7) d开始明显上升,至移植后第(28.5±2.2) d达到高峰,明显晚于对照组(P＜0.01).结论 抗CD40L单克隆抗体可抑制异种胰岛移植的排斥反应,延长受体大鼠和移植物的存活时间.     

供肝动脉变异和植入前动脉重建

目的探讨供肝动脉变异类型,术中损伤原因及植入前重建的方法。方法1993年10月至2004年12月,中山大学附属第三医院肝脏移植中心共行供肝切取和修整术600例,术中记录肝动脉变异类型和术中动脉误伤,重建变异肝动脉,形成单一的备吻合血管。结果在600例供肝中,19·2%(115/600)供肝动脉变异。53例(53/600)变异动脉须血管重建,其中39例(39/53)代替性或副肝右动脉来自肠系膜上动脉,1例(1/53)代替性肝右动脉来自腹腔干,5例(5/53)代替性或副肝左动脉来自胃左动脉,2例(2/53)变异肝左动脉和3例(3/53)变异肝右动脉离断后来源不清,3例(3/53)变异肝左和肝右动脉双重替代。6例(6/485)供肝切取术中意外损伤正常肝动脉,需要动脉重建。变异肝动脉损伤19例(19/115),均行动脉重建。动脉重建方法包括变异动脉与脾动脉(36/53)、胃十二指肠动脉(12/53)以及复杂的吻合方法(5/53)。结论供肝快速切取过程中,肝动脉变异增加肝动脉意外损伤发生率,损伤变异动脉均须在植入前重建。变异动脉重建方法的选择取决于肝动脉解剖学特点。     

肝移植术后乙肝病毒再感染的危险因素及对策

目的探讨肝移植术后乙型肝炎病毒再感染的危险因素和对策。方法对2003年9月到2004年12月间在我院肝脏移植中心施行肝移植术且符合研究标准的130例病例进行前瞻性研究，采用肌注剂型HBIg联合核苷类抗病毒药物联合预防HBV再感染并长期随访，分析HBV再感染的危险因素。结果130例中128例术后血清HBsAg转为阴性并检测到HBsAb，平均随访12．2个月，HBV再感染率为6．3％（8／128例）。结论肝移植术前HBeAg阳性、HBVDNA定量达到或超过10^5eopies／ml、术后1dHBsAg阳性及HBsAb〈200U／L是HBV再感染的危险因素。     

缺血预处理对大鼠肝脏部分切除术后残留肝脏的保护作用及其机制的研究

目的　探讨缺血预处理 (ischemicpreconditioning ,IPC)对大鼠肝脏部分切除术后残留肝脏的保护作用及其机制。方法　 5 0只雄性SD大鼠随机均分为假手术 (Sham)、单纯热缺血 (warmis chemia ,WI)、IPC、IPC L arginine(NO供体 )和WI NAME(NO合成酶抑制剂 ) 5组。术前、术后 1、2、3d检测血清AST和ALT ,术前、IPC后、热缺血后 0 5、1、2、3h检测肝脏组织NO浓度。AST和ALT用自动生化分析仪检测 ,NO用硝酸还原法检测。结果　WI、IPC、IPC L arginine及WI NAME组术后AST和ALT均高于Sham组 (P <0 0 5或P <0 0 1) ,IPC和WI NAME组术后AST和ALT低于WI和IPC L arginine组 (P <0 0 5 )。WI、IPC、IPC L arginine及WI NAME组术后 0 5h肝脏组织NO浓度开始升高(P <0 0 5或P <0 0 1) ,IPC和WI NAME组术后肝脏组织NO浓度低于WI和IPC L arginine组 (P <0 0 5 )。结论　IPC对大鼠肝脏部分切除术后残留肝脏的缺血再灌注损伤有保护作用。IPC通过抑制大鼠热缺血再灌注肝脏产生NO ,减少NO所诱发的肝脏组织细胞的凋亡或坏死 ,保护肝脏功能。     

老年女性低位直肠癌保肛手术的临床探讨

目的 探讨采用低位直肠癌根治性手术对老年女性患者是否切实可行。方法 对23例女性低位直肠癌患者，采用经腹行低位直肠癌直肠癌直肠前切除术，并在盆腔内实施超低位人工端端吻合术，保留肛门。结果 本组23例癌肿距肛门在5－6cm以内的病人术后效果良好，无并发症及副损伤出现。术后直肠指检证实吻合口距肛门仅2.5-3.0cm；术后均能维持良好的排便功能。23例均行定期复查及化疗，分别经1．5－2．0年的临床追踪，目前尚未发现复发情况。结论 根治性直肠癌直肠前切除及保留肛门的手术方式，对于老年女性低位直肠癌患者是有效可行的，从而提高其生活质量。     

西罗莫司对人肝癌裸鼠肝脏移植瘤生长的影响

Objective To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice. Methods HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus (FK506). The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected by immunohistology, microvessel density (MVD) was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynuclcotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Results The tumor weight was (352±38) mg, (683±53) mg and (675±45) mg in SRL, FKS06 and control group respectively. The tumor weight was significantly decreased in SRL group (P < 0.0 I), and there was no difference between FKS06 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group (P < 0.05), and it was not significantly different between FK506 group and control group (P > 0.05). Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group (P < 0.01). Conclusion SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.