川芎嗪对肝缺血再灌注损伤保护作用的实验研究

采用大鼠肝缺血再灌注损伤模型，观察了川芎嗪对肝缺血再灌注损伤的防护作用，结果提示川芎嗪可显著减少血清转氨酶，ＬＤＨ的溢出，减轻肝缺血再灌注后肝细胞病理性损伤，明量降低肝组织ＬＰＯ，ＴＸＢ２的升高，维持缺血及再灌注期ＳＯＤ活性，川芎嗪通过抑制肝缺血再灌注时氧自由基产生，提高组织抗氧化能力，维持Ｔ／Ｋ平衡，对肝缺血再灌注损伤起到保护作用。     

中性粒细胞在肝缺血再灌注损伤中的作用及川芎嗪的保护效应

目的探讨肝缺血再灌注损伤时中性粒细胞（ＰＭＮ）的聚集及川芎嗪的保护作用．方法应用家兔肝缺血再灌注损伤模型，观察肝缺血再灌注损伤过程中ＰＭＮ的浸润、脂质过氧化物（ＬＰＯ）、肝细胞形态学变化及川芎嗪的防护效应．结果随着肝缺血再灌注时间的延长，肝组织中ＰＭＮ浸润程度逐渐加重，肝细胞形态学异常变化越发显著，川芎嗪可明显减轻上述的异常变化．结论中性粒细胞聚集、粘附、活化是肝缺血再灌注损伤的重要原因，川芎嗪通过抑制ＰＭＮ聚集、粘附、活化而减轻肝缺血再灌注损伤．     

氧自由基在腹主动脉阻断所致内脏缺血再灌注损伤中的作用

目的探讨氧自由基在腹主动脉阻断所引起的肝、肾和小肠缺血再灌注损伤中的作用。方法建立在小猪腹腔动脉开口以上阻断腹主动脉的实验模型，检测在不同再灌注时点肝、肾、小肠组织及血液中丙二醛（ＭＤＡ）和ＳＯＤ的变化，同时检测主要肝肾功能和动脉血气分析的改变。结果在各再灌注时点血和组织中ＭＤＡ的含量升高，而ＳＯＤ的活性下降，多数时点同缺血前比较差异有显著性；再灌注２ｈ时血中谷丙转氨酶（ＡＬＴ）、尿素氮（ＢＵＮ）和肌酐（ＣＲＥ）较缺血前有明显升高，代谢性酸中毒也极为明显。结论氧自由基在腹主动脉阻断引起的多个脏器缺血再灌注损伤中起重要作用，且氧自由基的变化有一定的特点。     

川芎嗪对老龄鼠再灌注肾损伤中一氧化氮的作用研究

目的 观察川芎嗪对老龄鼠肾缺血再主中一氧化氮合酶（ＮＯＳ）和一氧化氮（ＮＯ）的影响及对肾脏的保护作用。方法 制做老龄鼠肾缺血再灌注模型,分为用川芎嗪组和未用川芎嗪组,检测缺血６０ｍｉｎ,再灌注１５ｍｉｎ和２４ｈ的肾组织ＮＯＳ、ＮＯ及丙二醛（ＭＤＡ）浓度。结果 缺血再灌注后肾组织中ＮＯＳ明显升高（Ｐ〈０．０１）,ＮＯ明显升高（Ｐ〈０．０１）,ＭＤＡ明显升高（Ｐ〈０．０１）,与此结果相比,用川芎嗪组Ｎ     

肝缺血再灌注损伤对乳酸脱氢酶活性的变化和川芎嗪的？…

目的：探讨肝缺血再灌注损伤（ＨＩＲＩ）时乳酸脱氢酶（ＬＤＨ）活性的改变及川芎嗪的保护作用。方法：制备ＨＩＲＩ模型，随机将２１只家兔发为三组（对照组，７只，盐水组，７只，川芎组，７只）观察血清及肝组织ＬＤＨ活性的动态变化及川芎嗪对它们的影响，结果：盐水组血清ＬＤＨ活性进行性升高，肝组织ＬＤＨ则明显下降，川芎组变化不明显，血清及肝组织ＬＤＨ活性与盐水组比较，均有显著性差异。结论：川芎嗪对ＨＩＲＩ时ＬＤ     

预处理对兔缺血再灌注损伤心肌的保护作用

目的：确定顶处理对兔缺血再灌注损伤心肌是否具有保护作用和氧自由基在兔预处理机制中的作用。方法：采用麻醉开胸兔急性心肌缺血再灌注损伤模型。心肌梗死面积和危险区分别采用组织学和荧光粒子技术测定。实验分４组：对照组（ｎ＝９），预处理组（ｎ＝８），高剂量超氧化物歧化酶预处理组（ＨＤＳＯＤ－ＰＣ，ｎ＝８）和低剂量超氧化物歧化酶预处理组（ＬＤ－ＳＯＤ－ＰＣ，ｎ＝９）。左冠状动脉回旋支４次５分钟缺血和５分钟再灌注完成预处理。对照用于３０分钟缺血后再灌注１２０分钟；其余各组在预处理后的缺血与再灌注同对照组。结果：梗死面积占危险区百分比在对照组与预处理组、ＨＤ－ＳＯＤ－ＰＣ组和ＬＤ－ＳＯＤ－ＰＣ组之间差异有统计学显著意义（Ｐ均＜０．０５）；预处理组、ＨＤ－ＳＯＤ－ＰＣ组和ＬＤ－ＳＯＤ－ＰＣ组之间差异无统计学显著意义。结论：预处理对兔缺血再灌注损伤心肌有保护作用，氧自由基在该预处理机制中不起明显作用。     

川芎嗪对肝缺血再灌注损伤大鼠P-选择素表达的影响

[目的]观察川芎嗪干预肝缺血再灌注损伤大鼠P-选择素表达,探索可能的病理机制,为预防治疗肝细胞缺血再灌注损伤提供依据.[方法]将64只SD大鼠随机分为4组,肉眼观察肝脏形态变化,光镜、电镜观察肝细胞形态变化,免疫组化SABC法检测肝组织中P-选择素表达.[结果]缺血再灌注组可见肝细胞水肿明显,伴空泡形成,间质充血水肿及炎性细胞浸润,再灌注6 h可见肝组织出现明显的点状坏死灶,并可见到灶性坏死;再灌注24 h肝组织可见多发性灶性坏死及片状坏死灶.川芎嗪干预组各时间点肝组织外观与正常肝相似,光镜下肝细胞无明显肿胀,有极少量空泡形成,但无变性或坏死,且间质无明显变化.免疫组化SABC法检测显示,缺血再灌注早期P-选择素即在肝组织中表达,与川芎嗪干预组及假手术组比较,差异有统计学意义(P＜0.01).缺血再灌注组P-选择素表达以1 h时最为明显,与再灌6 h及24 h相比,差异有统计学意义(P＜0.01).[结论]川芎嗪能有效抑制P-选择素的表达,减轻肝缺血再灌注损伤.P-选择素主要在缺血再灌注损伤早期表达.P-选择素介导中性粒细胞滚动黏附,可能是肝缺血再灌注损伤的主要机制之一.     

一氧化氮供体对离体大鼠心脏心肌缺血再灌注损伤不同时间的作用

目的：探讨在心肌缺血再灌注过程的不同时期补充一氧化氮（ＮＯ）对心肌损伤的影响。方法：以离体灌流大鼠心脏作为缺血（３０分钟）再灌注（６０分钟）模型。４８只心脏分为４组：Ａ组（ｎ＝１１）仅于再灌注期初２０分钟内给予硝酸甘油（ＮＯ供体）；Ｂ组（ｎ＝１２）于低流量缺血期及再灌注期初２０分钟内均给予硝酸甘油；Ｃ组（ｎ＝１４）为缺血再灌注对照组；Ｄ组（ｎ＝１１）仅于低流量缺血期给予硝酸甘油。测定心功能及肌酸激酶漏出量，同时测定心脏ＮＯ释放量。结果：Ｂ组及Ｄ组缺血后心功能的恢复明显低于Ｃ组和（或）Ａ组。Ｂ组缺血后冠状动脉流量的恢复显著低于Ａ组。Ｂ组及Ｄ组缺血再灌注期肌酸激酶漏出量明显大于Ｃ组及Ａ组。结论：Ｂ组对心肌组织的损伤最重；Ｄ组可损伤心肌细胞；Ａ组对心肌组织无损害。     

茶多酚对大鼠肝脏缺血-再灌注损伤的保护作用

目的探讨茶多酚对大鼠肝脏缺血再灌注损伤的保护作用及其机制。方法健康雄性SD大鼠30只，随机均分为4组：假手术正常对照组6只；肝脏缺血再灌注损伤模型组8只；茶多酚低浓度于预组8只（75mg／kg）；茶多酚高浓度于预组8只（150mg／kg）．缺血30min再灌注60min检测肝组织MDA含量、GSH-PX活性及血浆ALT含量。光镜下比较各组肝组织损伤情况。结果肝缺血再灌注模型组ALT、MDA含量明显高于假手术正常对照组（P〈0．01），GSH-PX活力则降低（P〈0．01）；茶多酚低浓度及高浓度组ALT，MDA含量均明显低于肝缺血再灌注模型组（P〈0．01），而GSH-Px活力均高于肝缺血再灌注模型组（P〈0．01）；光镜观察茶多酚低浓度及高浓度预处理组肝细胞损伤明显小于肝缺血再灌注模型组。结论茶多酚对大鼠肝脏缺血再灌注损伤具有显著的保护作用。     

丹参对大鼠肝硬化门脉高压缺血再灌注胃粘膜损伤的实验研究

实验制成大鼠肝硬化门脉高压（ＰＨＴ）缺血再灌注模型，用电子自旋共振技术测定缺血再注前后及丹参治疗后胃粘膜中氧自由基（ＯＦＲ）以及脂质过化物（ＬＰＯ）和超氧化物歧化酶（ＳＯＤ）的变化，同时光镜、电镜观察其病理改变，探讨丹参对胃粘膜再注损伤的防治作用。实验结果提示，ＰＨＴ胃粘膜较正常胃膜更易受缺血再灌注损伤，粘膜损伤的严重程度与ＯＦＲ、ＬＰＯ及ＳＯＤ密切相关；早期使用丹参可显著降低胃粘膜中ＯＦＲ及ＬＰ     

Mild hypothermia protects liver against ischemia and reperfusion injury

AIM: To determine whether mild hypothermia could protect liver against ischemia and reperfusion injury in pigs. METHODS: Twenty-four healthy pigs were randomly divided into normothermia, mild hypothermia and normal control groups. The experimental procedure consisted of temporary interruption of blood flow to total hepatic lobe for different lengths of time and subsequent reperfusion. Hepatic tissue oxygen pressure (PtiO2) and aspartate aminotransferase (AST) values were evaluated, and ultrastructural analysis was carried out for all samples. RESULTS: Serum AST was significantly lower, and hepatic PtiO2 values were significantly higher in the mild hypothermia group than in the normothermia group during liver ischemia-reperfusion periods (P= 0.032, P= 0.028). Meanwhile, the histopathologic injury of liver induced by ischemia-reperfusion was significantly improved in the mild hypothermia group, compared with that in the normothermia group. CONCLUSION: Mild hypothermia can protect the liver from ischemia-reperfusion injury in pigs.     

Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

AIM： To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. METHODS： Thirty rats were divided into three groups as sham （Group 1）, control （Group 2）, and Nigella sativa （NS） treatment group （Group 3）. All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS （0.2 mL/kg） intraperitoneally, before ischemia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrifi ced. Serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, and lactate dehydrogenase （LDH） levels were determined. Total antioxidant capacity （TAC）, catalase （CAT）, total oxidative status （TOS）, oxidative stress index （OSI） and my-eloperoxidase （MPO） in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. RESULTS： The levels of liver enzymes in group 3 weresignifi cantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were signifi cantly lower in group 3 than the group 2. Histological tissue damage was milder in the NS treatment group than that in the control group. CONCLUSION： Our results suggest that Nigella sativa treatment protects the rat liver against to hepatic ischemia-reperfusion injury.     

交感神经递质去甲肾上腺素与肝脏缺血再灌注损伤的研究进展

本文概述交感神经递质去甲肾上腺素在肝脏缺血再灌注损伤中的作用及相关机制。在肝脏缺血再灌注期间,交感神经兴奋去甲肾上腺素释放的增加具有双向作用,不仅可以促进炎症的进展,而且还有一定的肝脏保护作用,促进肝细胞再生。这一双向作用可能和去甲肾上腺素的释放量以及其作用于不同受体有关。进一步研究这双向机制对临床治疗肝脏缺血再灌注损伤有十分重要的意义。     

应用S-腺苷蛋氨酸预处理在大鼠肝脏缺血再灌注损伤中的保护作用

目的 研究S-腺苷蛋氨酸预处理对大鼠肝脏缺血再灌注损伤的保护作用及其机制.方法 将54只大鼠随机分为假手术组、缺血再灌注(I/R)组和S-腺苷蛋氨酸预处理(S-arleneyslmethioaine,SAM)组.SAM组大鼠缺血前2 h行腹腔注射SAM预处理.假手术组仅做分离,不阻断肝门;其余两组大鼠均在阻断肝门左、中...     

Suprahepatic vena cava manipulative bleeding alleviates hepatic ischemia–reperfusion injury in rats

BACKGROUND: Little is known about time course and peak level of reactive oxygen species in suprahepatic vena cava after liver ischemia-reperfusion. OBJECTIVE: To determine time course and peak level of reactive oxygen species in suprahepatic vena cava after liver ischemia-reperfusion. To focus on the effects of suprahepatic vena cava manipulative bleeding on the hepatic ischemia-reperfusion injury in rat model. METHODS: In experiment Part I, blood was taken from suprahepatic vena cava and infrahepatic vena cava for malondialdehyde detection at different time points after reperfusion. Furthermore, we treated the experimental rats in Part II by suprahepatic vena cava manipulative bleeding or infrahepatic vena cava manipulative bleeding at 10 min after reperfusion. RESULTS: In experiment Part I, malondialdehyde concentration in suprahepatic vena cava elevated obviously with time and peaked at 10 min after reperfusion. The numbers of accumulated polymorphonuclear neutrophils was significantly increased in ischemia-reperfusion group from 10 min after reperfusion, compared with sham-operated group. In Part II, 2% of body weight suprahepatic vena cava manipulative bleeding with blood transfusion at 10 min after reperfusion significantly decreased circulating malondialdehyde, tumour necrosis factor-alpha, endothelin-1, hyaluronic acid, alanine aminotransferase, aspartate aminotransferase levels and polymorphonuclear neutrophil infiltrations in the liver. The 7-day survival rate of this group was 68.75% (11/16) which was significantly higher than other groups. CONCLUSIONS: We provided the first evidence that 2% of body weight suprahepatic vena cava manipulative bleeding with blood transfusion at 10 min after reperfusion significantly prevented liver ischemia-reperfusion injury.     

Effects of Wy14643 on hepatic ischemia reperfusion injury in rats

AIM： To investigate the effects and possible mechanisms of Wy14643 on hepatic ischemiareperfusion （I/R） injury in rats. METHODS： Thirty male Sprague-Dawley rats weighing 220-280 g were randomly divided into five experimental groups： sham group （G1, n = 6）： a sham operation was performed （except for liver I/R）, I/R-untreated group （G2, n = 6）： rats underwent liver ischemia for 90 min followed by reperfusion for 4h; and I/R ＋ Wy14643 groups （G3, G4, G5; n = 6）： after the same surgical procedure as in group 2, animals were pretreated with Wy14643 at the dose of 1, 5 and 10 mg/kg 1 h before ischemia, respectively. Hepatic ischemia-reperfusion （I/R） was induced by clamping blood supply to the left lateral and median lobes of the liver for 90 min, and atraumatic clamp was removed for 4 h reperfusion. Blood samples and liver tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase （ALT）, aspartate aminotransferase （AST）, myeloperoxidase （MPO）, serum interleukin- 1β（IL-1β） and tumor necrosis factor alpha （TNF-α）, as well as activity of superoxide dismutase （SOD） and content of malondialdehyde （MDA） in the hepatic tissue homogenate. RESULTS： Hepatic I/R induced a significant increase in the serum levels of ALT, AST, TNF-α, IL-1β and MPO, as well as the levels of ALT, AST and MDA in the liver tissue homogenate, which were reduced by pretreatment with Wy14643 at the dose of 1, 5 and 10 mg/kg, respectively. The activity of SOD in the liver tissue homogenate was decreased after hepatic I/R, which was enhanced by Wy14643 pretreatment. In addition, serum and liver tissue homogenate ALT and AST in the Wy14643 10 mg/kg group were lower than in the Wy14643 1 mg/kg and 5 mg/kg groups, respectively. CONCLUSION： Wy14643 pretreatment exerts significant protection against hepatic I/R injury in rats. The protective effects are possibly associated with enhancement of anti-oxidant and inhibition inflammation res     

Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver

AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.     

甘氨酸对大鼠肝移植缺血再灌注损伤库普弗细胞CD14和核因子-κB的影响

目的 探讨甘氨酸对大鼠肝移植缺血再灌注损伤库普弗细胞CD14和核因子-κB(NF-κB)的影响。 方法 将大鼠分为肝移植缺血再灌注组、等渗盐水预处理组、甘氨酸预处理组,检测再灌注后受体存活率、肝脏功能和病理组织学改变。分离培养再灌注后库普弗细胞,检测细胞CD14 mRNA的表达、NF-κB活性、培养上清液肿瘤坏死因子α和白细胞介素-1分泌情况。 结果 甘氨酸预处理能明显提高大鼠术后1周存活率(x2值分别为6.67和8.57,P值均<0.0 1)、改善肝功能、减轻肝脏病理组织学改变;甘氨酸预处理能明显下调库普弗细胞CD14 mRNA的表达(F=7.64,P<0.01)、降低NF-κB活性(F=11.47,P<0.01)、减少上清液肿瘤坏死因子α和白细胞介素-1分泌(F值分别为14.08和9.56,P值均<0.01)。 结论 甘氨酸能够有效地减轻肝移植后缺血再灌注损伤,其机制可能与抑制库普弗细胞CD14表达和NF-κB活性、减少肿瘤坏死因子α和白细胞介素-1的分泌有关。     

Role of NK,NKT cells and macrophages in liver transplantation

Liver transplantation has become the treatment of choice for acute or chronic liver disease. Because the liver acts as an innate immunity-dominant organ, there are immunological differences between the liver and other organs. The specific features of hepatic natural killer(NK), NKT and Kupffer cells and their role in the mechanism of liver transplant rejection, tolerance and hepatic ischemia-reperfusion injury are discussed in this review.