精神分裂症患者的脑功能显像与神经心理测验的相关研究

本研究应用单光子发射断层摄影术（ＳＰＥＣＴ）、ＨＲ成套神经心理测验（成人）修订本［ＨＲＢ（Ａ）－ＲＣ］和修订韦氏记忆测验（ＷＭＳ－ＲＣ）对３２例住院精神分裂症患者的脑功能改变及脑功能显像与神经心理测验之关系进行探讨。结果显示，精神分裂症患者存在额叶、颞叶和基底节的脑血灌流量降低，同时表现程度不同的神经心理功能损害，此改变在阴性症状和阳性症状的病人间无差异。脑血灌流量降低与损伤指数（ＤＱ）和记忆商数（ＭＱ）未见明显关系。相关分析表明，ＤＱ与ＴＥＳＳ评分呈显著正相关（ｒ＝０．３６，Ｐ＜０．０５）；ＭＱ与住院次数（ｒ＝－０．４２，Ｐ＜０．０５）、ＢＰＲＳ评分（ｒ＝－０．５６，Ｐ＜０．０１）、ＳＡＰＳ评分（ｒ＝－０．３９，Ｐ＜０．０５）和ＳＡＮ评分（ｒ＝－０．３７，Ｐ＜０．０５）呈显著负相关，与ＧＡＳ评分（ｒ＝０．５３，Ｐ＜０．０１）呈显著正相关     

精氨酸加压素在内毒素热限形成中的作用

本文观察了家兔静脉注射不同剂量ＥＴ后中隔区，下丘脑组织及血浆中ＡＶＰ含量的变化。结果显示：在ＥＴ发热过程中，中隔区，下丘脑及血浆ＡＶＰ含量均显著增多（Ｐ＜０．０１）；ＥＴ发热达热限时，体温不再升高，中隔区与血浆ＡＶＰ含量也不再增多，且中隔区及血浆ＡＶＰ含量变化与体温变化呈明显正相关（ｒ＝０．９８４，０．０５＜Ｐ＜０．０１；ｒ＝０．９９４，Ｐ＜０．０１）；此时，下丘脑升高的ＡＶＰ含量开始下降（Ｐ０。     

急性脑血管病患者血浆内皮素水平升高的意义以及与血管紧张素Ⅱ、心钠素关系的探讨

我们用放射免疫分析（ＲＩＡ）测定了２５名健康志愿者和２８例急性脑卒中病人（脑出血１２例、脑梗塞１６例）血浆内皮素（ＥＴ）、心钠素（ＡＮＰ）和血管紧张素Ⅱ（ＡＴⅡ）的含量。急性脑卒中病人的血浆ＥＴ、ＡＴⅡ均高于正常对照（Ｐ＜０．０１），ＡＮＰ含量则低于正常对照（Ｐ＜０．０１），脑出血与脑梗塞患者血浆上述指标差异不明显。同时发现基底节区病变者血浆ＥＴ虽然比正常高，但无统计学意义，而大脑皮层和其它部位病变者则明显高于正常对照（Ｐ均＜０．０１），且血浆ＥＴ和ＡＴⅡ均与ＡＮＰ成负相关（ｒ＝－０．４８和－０．４７，Ｐ＜０．０１），血浆ＥＴ和ＡＴⅡ之间成正相关（ｒ＝０．５６，Ｐ＜０．０１）．结果提示，ＥＴ与急性脑卒中病人的发病及部位有关，且与血管活性多肽（如ＡＮＰ、ＡＴⅡ）之间存在明显的相关性。     

血浆内皮素—1和肿瘤坏死因子与急性心肌梗塞的关系

本文对２０例急性心肌梗塞（ＡＭＩ）患者检测了血浆内皮素－１（ＥＴ－１）和肿瘤坏死因子（ＴＮＦ）的水平，结果表明，ＡＭＩ组的ＥＴ－１、ＴＮＦ均较正常对照明显升高（Ｐ〈０．００１），且二者与肌酸磷酸激酶的ＭＢ同功酶（ＰＣＫ－ＭＢ）均呈正相关（ｒ＝０．０６９８４，Ｐ〈０．００１；ｒ＝０．６０５３，Ｐ〈０．０１）。研究结果说明ＥＴ－１和ＴＮＦ参与了ＡＭＩ的病理损伤过程。     

非胰岛素依赖型糖尿病人血浆内皮素水平与游离脂肪酸浓度的关系

为探讨非胰岛素依赖型糖尿病（Ｎｏｎｉｎｓｕｌｉｎ－ｄｅｐｅｎｄｅｎｔｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓ,ＮＩＤＤＭ）人内皮细胞损伤的可能机制,作者采用放射免疫法和反相高效液相色谱技术（ＨＰＬＣ）同时测定了３４例正常人和５６例ＮＩＤＤＭ病人血浆内皮素（ＥＴ）和游离脂肪酸（ＦＦＡ）浓度。结果显示：ＮＩＤＤＭ病人血浆ＥＴ和ＦＦＡ浓度较正常对照明显升高（均ｐ＜０．０１）,且血浆ＥＴ与空腹血糖（ＦＢＧ）水平和ＦＦＡ总浓度呈明显正相关（ｒ＝０．３２４和,ｒ＝０．３５１,均Ｐ＜０．０１）。结果提示：ＮＩＤＤＭ患者高血糖、脂肪酸代谢紊乱及胰岛素抵抗在其血管内皮损伤中可能有重要作用。     

高血压患者离体胃动脉平滑肌细胞内心钠素和内皮素的测定

采用正常血压者（ＮＴ）和高血压患者（ＥＨ）的离体动脉血管，并分离，培养动脉平滑肌细胞（ＡＳＭＣ），观察了ＡＳＭＣ合成和分泌心钠素（ＡＮＰ）内皮素（ＥＴ）的情况，探讨它们之间的相互关系及在高血压发病中的作用，结果发现：体外培养和ＡＳＭＣ能够合成和分泌ＡＮＰ，ＥＴ。ＥＭ组ＡＳＭＣ及培养液中的ＡＮＰ和ＥＴ含量显著高于ＮＴ组（Ｐ〈０．０１），ＥＴ与ＡＮＰ呈显著正相关（ｒ＝０．９２，Ｐ〈０．０１）ＥＴ与收缩     

冠状动脉造影后血浆肾上腺髓质素的改变

本文研究冠状动脉造影前后血浆肾上腺髓质素（ＡＤＭ １３－ ５２）及内皮素（ＥＴ－ １）水平。用特异性放射免疫法测定冠状动脉正常人和冠状动脉病患者，冠脉造影前后血浆ＡＤＭ（１３－５２）及ＥＴ－１含量。结果表明冠脉造影后即刻血浆ＡＤＭ（１３－５２）和ＥＴ－１均明显升高，ＡＤＭ（１３－５２）从基础时３１．２３ ±１．１２ｐｇ／ｍＬ升高到４０．９１±１．２８ｐｇ／ｍＬ（Ｐ＜０．００１），ＥＴ－１从８８．８４±１０．５８ｐｇ／ｍＬ升高到１５８．２６ ± １３．６６ｐｇ／ｍＬ（Ｐ＜０．０１）。正常组及冠脉病组冠造术后血浆ＡＤＭ（１３－５２）及ＥＴ－１均较术前明显升高；但两组间比较，无论冠脉造影前后，ＡＤＭ或ＥＴ－１均无显著差异。ＡＤＭ（１３－５２）与ＥＴ－１的变化呈中等度的正相关（ｒ＝０．４４８４， Ｐ＜ ０． ００１）。因此，冠脉造影可使ＡＤＭ（１３－５２）及ＥＴ－１均升高，可能与造影剂对血管刺激、导管直接对血管内皮的刺激及交感神经兴奋性增高有关。ＥＴ—１可能作为一种中介因子，与冠脉造影的部分并发症有关，而与之作用相反的ＡＤＭ（１３－５２）升高可能是机体维持自身稳定的一种代偿性保护机制。     

缺血再灌注时大鼠心肌局部血管紧张素Ⅱ的变化及其与能量代谢的关系

本实验用高效液相色谱法测定了不同缺血／再灌注条件下心肌组织内高能磷酸化合物的含量，并用放色法测定了大鼠心肌组织内血管紧张素Ⅱ（ＡＴ－Ⅱ）的含量。结果表明：缺血３０ｍｉｎ和缺血４０ｍｉｎ组ＡＴ－Ⅱ明显高于缺血１５ｍｉｎ组（Ｐ＜０．０５），再灌后ＡＴ－Ⅱ含量进一步升高，此变化与在缺血再灌注过程中的高能磷酸化合物改变恰好相反。在缺血４０ｍｉｎ再灌２０ｍｉｎ组的灌流液中预先加入血管紧张素转换酶抑制剂－巯甲丙脯酸，则心肌中磷酸肌酸（ＰＣｒ）、三磷酸腺苷（ＡＴＰ），ＴＡＮ（ＡＭＰ＋ＡＤＰ＋ＡＴＰ）与能荷Ｅ（１／２ＡＤＰ＋ＡＴＰ／ＴＡＮ）均非常显著高于未加巯甲丙脯酸组（Ｐ＜０．００１），可见心肌缺血／再灌注时心肌高能磷酸化合物含量的变化与肾素－血管紧张素系统关系密切，两者呈显著负相关（ｒ＝－０．８３）。抑制ＡＴ－Ⅱ的生成能有效地保护缺血心肌的能量贮备     

肾上腺髓质素对内皮素促家兔气道平滑肌细胞增殖的抑制作用

在体外培养的家兔气道平滑肌细胞（ＡＳＭＣ）上，观察肾上腺髓质素（ＡＭ）对内皮素（ＥＴ）促ＡＳＭＣ增殖的影响及丝裂素活化蛋白激酶（ＭＡＰＫ）活性的变化。以探讨ＡＭ对ＡＳＭＣ增殖的调控。结果显示１０－８ｍｏｌ／ＬＥＴ－１显著刺激ＡＳＭＣ３Ｈ－ＴｄＲ参入及ＭＡＰＫ激活（Ｐ＜０．０１）。ＡＭ（１３－５２）呈剂量依赖地抑制ＥＴ－１的上述作用（Ｐ＜０．０５，Ｐ＜０．０１）。单独应用ＡＭ（１３－５２）对ＡＳＭＣ３Ｈ－ＴｄＲ参入及ＭＡＰＫ活性无明显影响。表明ＡＭ（１３－５２）可抑制ＡＳＭＣ对ＥＴ－１的增殖反应，其机理可能涉及ＭＡＰＫ活性的抑制。     

抗退饮对LP性发热家兔的下丘脑cAMP含量及脑腹中隔区AVP含量的影响

目的：探讨抗退饮解热机制。方法：建立家兔ＬＰ 发热模型,观察抗退饮灌胃对家兔体温的影响和用放射免疫分析法检测腹 中隔ＡＶＰ 含量及下丘脑ｃＡＭＰ 含量的变化。结果：（１） 抗退饮灌胃＋ 静注ＬＰ 组的△Ｔ 为（０－５１ ±０－２５） ℃、中隔区ＡＶＰ 含量为（１１－９５ ±４－５２） ｐｇｍｇ 、下丘脑ｃＡＭＰ 含量为（０－９１３ ±０－４５０） ｐｍｏｌｍｇ 、分别低于ＮＳ 灌胃＋ 静注ＬＰ 组的△Ｔ（１－１８ ±０－２７） ℃、中隔区ＡＶＰ 含量（２２－３７ ±３－５８） ｐｇｍｇ 、下丘脑ｃＡＭＰ 含量（１－５６２ ±０－３６０） ｐｍｏｌｍｇ（ Ｐ＜０－０１） 。（２） 中隔区ＡＶＰ 含量变化与体温变化呈明显正相关（ｒ ＝ ０－７８２ ,Ｐ＜ ０－０１） 。结论：抗退饮解热机制可能是通过抑制下丘脑ｃＡＭＰ 含量升高,同时促进腹中隔ＡＶＰ 释放两种途径发挥作用     

肢体缺血预处理大鼠肝损伤保护效应中内皮素1的变化和意义

背景：研究体内最强的缩血管物质内皮素1在肢体缺血预处理保护大鼠肢体缺血再灌注后肝损伤中的变化和意义,有助于从肝脏微循环角度探讨肢体缺血预处理的保护作用。 目的：探讨内皮素1在肢体缺血预处理保护大鼠肢体缺血再灌注后肝损伤中的变化和意义。 方法：雄性Wistar大鼠随机分为对照组、肢体缺血再灌注组和肢体缺血预处理组。肢体缺血预处理组以橡皮带预先阻断双后肢血流5 min,然后恢复血流灌注5 min,反复4次进行缺血预处理。然后肢体缺血再灌注组和肢体缺血预处理组以橡皮带环绕结扎大鼠双后肢根部,阻断血流4 h后松解,恢复血流灌注4 h制备肢体缺血再灌注模型,并于再灌注前20 min于左侧颈外静脉插管滴注生理盐水。对照组双后肢松弛环绕橡皮带但不阻断血流,其后操作同肢体缺血再灌注组。 结果与结论：大鼠肢体缺血再灌注后血浆内皮素1、透明质酸酶、丙二醛、谷丙转氨酶、谷草转氨酶水平和肝组织内皮素1、丙二醛、髓过氧化物酶水平均明显升高(P < 0.05),肢体缺血预处理干预后上述指标均明显降低(P < 0.05)。光镜下可见肢体缺血再灌注组肝细胞肿胀,肝索排列不规则;肢体缺血预处理组上述损伤表现减轻。结果可见大鼠肢体缺血预处理对肢体缺血再灌注后肝损伤的保护作用可能与抑制了内皮素1的缩血管作用从而改善肝脏的微循环有关,也可能与内皮素1含量的降低减少了白细胞过度聚集活化和减弱脂质过氧化有关。     

Increased sinusoidal resistance is responsible for the basal state and endothelin-induced venoconstriction in perfused cirrhotic rat liver

The localization of increased intrahepatic vascular resistance and the segmental vascular responsiveness to endothelin-1 are not well known in liver cirrhosis. We determined the segmental vascular resistances and their response to endothelin-1 of isolated portally perfused bile duct ligation (BDL)-induced cirrhotic rat livers. The portal occlusion pressure (Ppo) and the hepatic venous occlusion pressure (Phvo) were obtained by analyzing the profiles of the portal (Ppv) and hepatic venous (Phv) pressures during the double occlusion maneuver of simultaneous occlusions of the inflow and outflow perfusion lines. From the pressure gradients among Ppv, Ppo, Phvo, and Phv, the portal-hepatic venous resistance was assigned to three segments of the portal [Rpv = (Ppv − Ppo)/blood flow (Q)], sinusoidal [Rsinus = (Ppo − Phvo)/Q] and hepatic venous [Rhv = (Phvo − Phv)/Q] resistances. Rsinus, but not Rpv or Rhv, was significantly greater in BDL livers than in sham livers. Endothelin-1 (0.1–1 nM) increased Rpv and Rsinus to a similar magnitude, but not Rhv, in both sham and BDL. At 3 nM, the responsiveness of Rpv was smaller in BDL than in sham, but that of Rsinus were similar between in BDL and sham. In conclusion, increased sinusoidal resistance accounts for increased intrahepatic resistance of BDL-induced liver cirrhosis. Endothelin-1 contracts portal veins and sinusoids, but not hepatic veins, in both sham and cirrhotic livers. Sinusoidal contractility to endothelin-1 is not impaired in cirrhotic livers.     

丹参对大鼠移植肝血红素氧合酶1表达的影响

背景：器官移植前使用丹参预处理能够保护组织缺血-再灌注损伤,改善移植器官存活率。 目的：观察含丹参的冷灌注液对同种异体大鼠移植肝脏中血红素氧合酶1表达的影响,以及对供体肝脏缺血-再灌注损伤的保护作用。 方法：将SD雄性大鼠随机分成UW液组(术中使用UW液灌注保存)、丹参+UW液组(术中使用丹参+UW液灌注保存)、ZnPP预处理组(移植前24 h腹腔内注射ZnPP,术中使用丹参+UW液灌注保存),建立稳定的大鼠同种异体肝移植模型。同时取10只正常大鼠作为正常对照。 结果与结论：丹参+UW液组和UW液组血清总胆红素、谷丙转氨酶、谷草转氨酶水平明显低于ZnPP预处理组(P < 0.01)。血红素氧合酶1mRNA及其蛋白在丹参+UW液组中较UW组表达更明显,在ZnPP预处理组中表达明显受到抑制(P< 0.05)。丹参+UW液组肝脏Suzuki标准评分明显低于ZnPP预处理组及UW液组(P < 0.05)。表明丹参能上调同种异体的大鼠移植肝脏中血红素氧合酶1 mRNA及其蛋白的表达,减轻供肝缺血-再灌注损伤,保护移植大鼠肝脏。     

核黄素预处理减轻大鼠肝缺血再灌注损伤

目的: 探讨核黄素对肝缺血再灌注损伤的影响及其机制。方法: 将24只SD大鼠随机分为3组,每组8只。假手术对照组(sham组)和缺血再灌注组(I/R组)大鼠喂以正常饲料,核黄素预处理组(R+I/R组)大鼠补充核黄素。喂养4周后,阻断大鼠肝门1 h,再灌注1 h建立I/R模型。术后采血并收集肝脏标本,分别检测血清及肝组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)水平和血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)的活性;蛋白印迹法检测肝组织血红素加氧酶-1(HO-1) 表达情况;HE染色观察肝组织病理学改变。结果: 与sham组比较,I/R组大鼠血清AST、ALT活性及MDA水平均明显升高,SOD活性显著降低(P<0.01);肝组织中SOD活性亦明显下降(P<0.01),MDA水平及HO-1蛋白表达则显著增高(P<0.05)。而R+I/R组较I/R组大鼠血清AST、ALT活性及MDA水平均明显下降,SOD活性显著增强(P<0.01);肝组织中MDA水平亦明显降低,SOD及HO-1蛋白表达显著增高(P<0.01)。组织切片显示I/R组大鼠肝细胞肿胀,炎症细胞浸润,小叶结构紊乱;R+I/R组大鼠肝细胞仅轻度肿胀,几乎无气球样变,小叶结构清晰。结论: 核黄素预处理对缺血再灌注肝脏具有显著的保护作用,其作用机制可能与核黄素通过降低MDA水平、提高SOD活性及HO-1蛋白表达,增强肝脏的抗氧化能力,减轻脂质过氧化反应有关。     

乙酮可可碱对大鼠肝脏缺血／再灌注损伤影响的实验研究

目的探讨乙酮可可碱保护大鼠肝缺血／再灌注损伤的机制。方法采取大鼠第一肝门阻断的缺血再灌注模型,将健康雄性SD大鼠64只随机分为四组：对照组及乙酮可可碱给药组,观察每组动物的病理切片,分别检测血浆谷丙转氨酶（ALT）、乳酸脱氢酶（LDH）、肿瘤坏死因子-α（TNF-α）以及肝组织匀浆中内皮素-1（ET-1）的含量,免疫组化测定P-选择素的表达。结果肝脏缺血／再灌注后,病理有明显的损伤改变。PTX保护组再灌注2、4h血清ALT、LDH、TNF-α和肝组织匀浆中ET-1含量与对照组相比显著降低（P〈0．01）,PTX保护组P-选择素蛋白表达显著低于对照组（P〈0．01）。结论肝脏微循环障碍是肝脏缺血／再灌注损伤的病理基础,给予PTX预处理可降低TNF-α、ET-1产生和减少P-选择素表达,从而减轻肝脏损伤。     

Non-invasive measurement of hepatic oxygenation by an oxygen electrode in human orthotopic liver transplantation

Precise evaluation of graft reperfusion is difficult in clinical liver transplantation. The oxygen electrode (OE) is a novel technique to detect blood flow indirectly by measuring the quantity of oxygen which can diffuse from the hepatic tissue to the surface electrode. Application of the surface OE does not influence the liver blood flow or parenchymal perfusion. Adequate graft oxygenation is essential to the outcome of organ transplantation and has not previously been analysed intra-operatively in liver transplant recipients. The OE was applied to the surface of the graft intra-operatively in 22 human liver grafts after restoring portal vein and hepatic artery inflow. OE readings were compared with liver blood flow using an electromagnetic flowmeter (EMF). Intra-operative haemodynamics and donor organ parameters known to influence graft function were correlated with the OE readings. There was a significant correlation (r=0.89; p<0.001, n=14) between tissue oxygenation using the OE and total liver blood flow measured by EMF. The tissue oxygenation measurements were reproducible with a coefficient of variation of 5%. The hepatic tissue oxygenation increased significantly from baseline following venous reperfusion of the graft (282+/-23 vs 3107+/-288 (+/-SE) nA, p<0.001). Hepatic arterial revascularisation resulted in a significant (p<0.001) increase of 41+/-7% in liver oxygen perfusion. There was significant negative correlation (r=0.80, p<0.001, n=22) between cold ischaemic time and graft tissue oxygenation. The OE provides a reliable, cheap and non-invasive method of monitoring liver graft oxygenation and perfusion during transplantation.     

Matrine protects sinusoidal endothelial cells from cold ischemia and reperfusion injury in rat orthotopic liver transplantation

The effect of matrine on cold ischemia and reperfusion injury of sinusoidal endothelial cells (SEC) was investigated in rats using an orthotopic liver transplantation (OLT) model. Syngeneic Sprague-Dawley (SD) rats were randomly assigned to 4 groups of 32 rats: untreated group (controls), low-dose treated group, high-dose treated group, and sham operation group (normals). After 5 hr of preservation in Ringer's solution, orthotopic implantation of the donor liver was performed. At 1, 2, 4, and 24 hr after reperfusion, 6 rats from each group were killed to collect blood and to excise the median hepatic lobe; the other 8 rats were observed to assess the 1-wk survival rate post-transplantation. All transplant recipients in the untreated group (controls) died within 48 hr, mostly between 10 to 20 hr. Matrine treatment increased the 1-wk survival rate to 75% in both treated groups. Plasma levels of hyaluronic acid (HA) at 1, 2, and 4 hr post-implantation were decreased significantly by matrine treatment. The immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in rat liver decreased significantly in both treated groups, and the pathological changes of SEC were ameliorated. Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). Hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were improved by matrine administration. In conclusion, matrine can protect SEC from cold ischemia and reperfusion injury after rat orthotopic liver transplantation.     

大鼠肝脏冷缺血再灌注损伤时姜黄素后处理对肝细胞凋亡的影响

背景:姜黄素预处理可减轻肢体缺血再灌注对肝脏的损伤,但姜黄素后处理对肝脏冷缺血再灌注损伤是否有保护作用及其机制目前研究甚少。目的:探讨大鼠肝脏冷缺血再灌注损伤时姜黄素后处理对肝细胞凋亡的影响。方法:选取成年雄性SD大鼠80只,采用随机数字表法将其分成4组(n=20):假手术组、冷缺血再灌注组、姜黄素后处理组、地塞米松组。使肝脏血流处于完全阻断状态,随后以脾静脉作为流入道和右肾上腺静脉作为流出道注入0℃复方乳酸林格液,冷灌注30min;停止冷灌注后,结扎近端脾静脉和右肾上腺静脉,切除脾脏,随即恢复肝脏血流,完成制作冷缺血再灌注模型。在大鼠冷缺血30min后,姜黄素后处理组经尾静脉注射姜黄素60 mg/kg,地塞米松组尾静脉注射地塞米松0.5 mg/kg,其他组以等量的生理盐水替代。再灌注6 h时经下腔静脉取血,检测血清天门冬氨酸氨基转移酶、丙氨酸转移酶水平,随后处死大鼠,取肝组织检测丙二醛水平;采用苏木精-伊红染色观察肝脏病理变化;Hoechst33258染色法检测肝细胞凋亡指数;Westernblot检测肝组织Bcl-2和Bax蛋白表达;RT-PCR检测肝组织促细胞凋亡基因Caspase-9m RNA表达;ELISA检测肝组织肿瘤坏死因子α及白细胞介素1β水平。结果与结论:①与假手术组比较,冷缺血再灌注组天门冬氨酸氨基转移酶、丙氨酸转移酶、丙二醛和凋亡指数明显升高(P<0.05);苏木精-伊红染色切片可见肝血窦内有大量炎性细胞浸润,肝细胞嗜酸性变,胞浆内疏松化,肝细胞呈气球样变,偶可见斑片状坏死,散在点状坏死灶;Bcl-2表达下降,Bax表达明显升高(P<0.05);Caspase-9 mRNA表达、肿瘤坏死因子α及白细胞介素1β水平明显升高(P<0.05);②与冷缺血再灌注组比较,姜黄素后处理组天门冬氨酸氨基转移酶、丙氨酸转移酶、丙二醛和凋亡指数明显下降(P<0.05);苏木精-伊红染色可见肝血窦内炎性浸润明显减轻,胞浆嗜酸性变和气球样变的肝细胞明显减少,但偶可见少量散在的点状坏死;Bcl-2表达升高,Bax表达明显下降(P<0.05);Caspase-9 mRNA表达、肿瘤坏死因子α及白细胞介素1β水平明显下降(P<0.05);③姜黄素后处理组上述各指标与地塞米松组比较差异无显著性意义(P>0.05);④综上所述,姜黄素后处理可减轻大鼠肝脏冷缺血再灌注损伤,其作用机制可能通过上调Bcl-2/Bax比值,抑制凋亡启动子Caspase-9mRNA的表达,减少炎性因子肿瘤坏死因子α和白细胞介素1β的释放,发挥抗凋亡的肝保护作用。     

The Groningen Hypothermic Liver Perfusion Pump: Functional Evaluation of a New Machine Perfusion System

To improve preservation of donor livers, we have developed a portable hypothermic machine perfusion (HMP) system as an alternative for static cold storage. A prototype of the system was built and evaluated on functionality. Evaluation criteria included 24 h of adequate pressure controlled perfusion, sufficient oxygenation, a maintained 0–4°C temperature and sterile conditions. Porcine livers were perfused with pump pressures that were set at 4 mmHg (continuous, portal vein) and 30/20 mmHg, at 60 BPM (pulsatile, hepatic artery). Control livers were preserved using the clinical golden standard: static cold storage. In the HMP group, pressure, flow and temperature were continuously monitored for 24 h. At time-points t = 0, 2, 4, 8, 12, and 24 h samples of University of Wisconsin machine preservation solution were taken for measurement of partial oxygen pressure (pO₂) and lacto-dehydrogenase. Biopsies in every lobe were taken for histology and electron microscopy; samples of ice, preservation solution, liver surface, and bile were taken and cultured to determine sterility. Results showed that temperature was maintained at 0–4°C; perfusion pressure was maintained at 4 mmHg and 30/20 mmHg for portal vein and hepatic artery, respectively. Flow was approximately 350 and 80 ml/min, respectively, but decreased in the portal vein, probably due to edema formation. Arterial pO₂ was kept at 100 kPa. Histology showed complete perfusion of the liver with no major damage to hepatocytes, bile ducts, and non-parenchymal cells compared to control livers.The machine perfusion system complied to the design criteria and will have to demonstrate the superiority of machine perfusion over cold storage in transplant experiments.     

灌注速度对移植肝脏缺血再灌注的损伤

背景：近年来有学者研究发现供体灌注的压力可直接影响移植物的能量代谢从而影响其活力,适当的灌注压力能明显提高供体的质量。 目的：观察不同灌注速度对大鼠移植肝脏再灌注损伤的影响。 方法：采用改良的Kamada双袖套法建立SD→SD原位肝移植模型。供体肝脏获取时分别以50,100,150,200 mL/h进行灌注。检测移植后外周血清肿瘤坏死因子α和谷丙转氨酶水平,观察肝脏组织病理学改变和肝脏组织内皮源性一氧化氮合酶的表达变化。 结果与结论：与低灌注速度相比,供体肝脏制备过程中200 mL/h的灌注速度导致了更加明显的肝脏病理形态学改变,肝细胞变性、肝血窦扩张和炎细胞浸润也更加明显。术后24 h肝功能的检测也发现,150,200 mL/h灌注速度组外周血谷丙转氨酶活性、肿瘤坏死因子水平明显高于50,100 mL/h灌注速度组(P < 0.05,P < 0.01),内皮源性一氧化氮合酶表达明显低于50,100 mL/h灌注速度组(P < 0.01),100 mL/h灌注速度后,随着灌注速度的增加肝功能损伤也明显加重。证实适当的灌注压力和速度是获得高质量供体的保障,能够减轻移植后肝功能损伤,改善受体预后,在大鼠肝移植供体制备过程中    100 mL/h是适宜的灌注速度。