大鼠小肠缺血再灌注后肾脏损伤

通过对２０只大鼠小肠缺血再灌注模型和肾组织中脂质过氧化物的测定,并结合病理改变,以探讨小肠缺血再灌注后肾损伤的病理机制。结果表明：大鼠小肠缺血再灌注后,血脂质过氧化物明显升高,同时关浆内脂质过氧物明显高于对照组。提示小肠缺血再灌注后肾组织细胞确有明显损伤,其中氧自由基对肾组织的破坏可能是肾脏病理生理改变的主要因素。     

局部降温预防骨骨各肌再灌注伤的实验研究及临床应用

缺血再灌注伤的预防方法已有较多研究，但用局部降温方法者则少见报道。将１６只日本大耳兔随机分成四组。每组一侧后肢降温后上止血带为实验组，另一侧后肢不降温上止血带作对照组。甲乙两组缺血４ｈ，分别再灌注１和２ｈ；丙丁两组缺血５ｈ，再分别灌注１和２ｈ。用针极温度传感器测得降温后深部肌温平均为１６．６℃。去除止血带再灌注后，取双侧股静脉血作钾、乳酸、超氧化物歧化酶及脂质过氧化物检测，并取腓肠肌作光镜和电镜组织学检查。结果发现，降温组血钾、乳酸及脂质过氧化物均低于对照组，经统计学处理有显著差异（Ｐ＜０．０１）；超氧化物岐化酶高于对照侧，有显著差异（Ｐ＜０．０１）。光镜及电镜亦发现降温组横纹肌结构损害较轻，属可逆性损害范围，肌细胞有再生可能。临床应用４５例。四肢手术前将深部肌温降到２２．４℃左右，使用止血带时间平均２ｈ５７ｍｉｎ，最长达４ｈ３１ｍｉｎ，其中９例术后指尖出现一过性麻木，未发现皮肤、肌肉及神经损害。证实，局部降温确有预防或减轻再灌注伤的作用。     

E-SELECTIN AND L-SELECTIN BLOCKADE IN PURE SKIN FLAPS EXPOSED TO ISCHAEMIA AND REPERFUSION INJURY

The inflammatory recruitment of leucocytes is a main cause of tissue damage in ischaemia/reperfusion (I/R) injury. Under appropriate flow conditions, E-selectin and L-selectin participate in the initial deceleration of neutrophils (PMNs) on inflamed endothelial cells before transmigration of PMNs into the surrounding tissue. Previous work from our lab showed increased survival of I/R injured myocutaneous flaps after treatment with anti-E/L-selectin. In this study, we have evaluated a combined antibody to E-selectin and L-selectin (EL-246) in porcine pure skin flaps exposed to I/R injury. Buttock skin flaps were exposed to eight hours of ischaemia and 20 hours of reperfusion. EL-246 or saline was given intra-arterially into the flaps. Estimated surviving area was not improved in the treated group. The lack of effect of EL-246 supports our suspicion that different mechanisms are involved in I/R injury in myocutaneous flaps compared with pure skin flaps. As a certain shear stress must be present for the selectins to exert their effect, a possible explanation for the diverse results in muscle and skin might be different reflow patterns.     

兔肝缺血/再灌注损伤肝组织氧压及线粒体形态观察

目的　观察兔肝缺血 /再灌注损伤不同时相肝组织氧压及线粒体形态变化 ,研究常温下肝脏缺血 /再灌注的损伤及其机制。方法　 4 0只兔随机分为 2组即缺血组和对照组。组织气体分析仪持续测定兔肝组织氧压 (Hepatic tissue oxygeonpressure Ptio2 ) ;电镜观察肝脏病理及线粒体形态改变 ,图像分析仪对线粒体的立体形态计量分析。结果　缺血组兔在肝脏缺血后肝 Ptio2值开始下降 ,再灌注 6 0 min时肝 Ptio2仍未恢复正常 (P<0 .0 5 )。电镜观察发现 :肝缺血 30 min,线粒体肿胀、内质网扩张 ,再灌注 6 0 m in后线粒体肿胀进一步加重 ,部分线粒体破坏 ,结构不清 ,线粒体空泡变性。兔肝缺血再灌注损伤后肝细胞线粒体与对照组相比 ,其比表面减小、平均体积增大 (P<0 .0 5 )。结论　常温下入肝血流阻断可以导致肝脏缺血 /再灌注后肝细胞功能障碍和病理损害。其作用机制与缺血期肝细胞缺氧、再灌注期肝脏微循环障碍和肝细胞线粒体的损伤有关     

离体睾丸缺血再灌注损伤的实验研究

目的 探讨人离体睾丸缺血再灌注损伤的变化规律。了解益生注射液对其变化的干预效果。方法 采用13人摆脱赠尸睾丸26只,用4℃250ml高渗枸橼酸盐嘌呤液冷保存,再以此液500ml再灌注,实验组用含500μg/ml益生注射液同法操作,同一睾丸于单纯冷保存（对照组睾丸8只,实验组8只）6、12、18、24、36、48、60和72小时连续取材,冷保存6、12、18、24和36小时（对照组与实验组每时间点各1只,共10只）后,37）复温再灌注6和12小时连续取材,作组织学及酶组织化学染色。结果 实验组睾丸组织4℃冷保存24小时内无明显病理改变;36和48小时后出现精索血管内皮细胞肿胀,变性及部分脱落,曲细精管与生精上皮剥离,间质轻度水肿等损伤;冷保存12小时乳酸脱氢酶与琥珀酸脱氢酶活性增高,24小时后又降低;一氧化氮合成酶活性于冷保存18小时后降低再灌注后组织损伤加重,对照组睾丸单纯冷保存12小时即出现精索血管内皮细胞肿胀,变性,24小时后加重,再灌注后精索血管大量内皮细胞变性脱落,曲细精管基膜剥离和间质水肿严重。结论 4℃冷保存24小时内仅有内皮细胞轻微损伤,超过24小时可引起睾丸血管及组织形态结构明显异常,37℃复温再灌注使损伤程度加重,益生注射液使人离体睾丸在4℃冷保存24小时内保持正常形态结构。且对再灌注损伤有保护作用。     

枯否细胞和肝脏缺血再灌注损伤

目的 了解枯否细胞在肝脏缺血再灌注损伤中的作用。方法 采用文献回顾的方法对枯否细胞在肝脏缺血再灌注损伤中的作用加以综述。结果 活化后的枯否细胞可产生和释放多种介质直接或间接地影响肝脏微循环。结论 枯否细胞在肝缺血再灌注损伤中发挥了重要作用。     

INHIBITION OF TISSUE FACTOR EXPRESSED BY ISCHAEMIC CARDIOMYOCYTES REDUCES INFARCT SIZE AFTER MYOCARDIAL ISCHEMIA/REPERFUSION INJURY

OBJECTIVE: To determine whether lipid‐modifying therapy with atorvastatin improves impaired endothelial function in patients with nephrotic range proteinuria (NRP). METHODS: A sequential, open‐label study of the effects of atorvastatin on dyslipidaemia and endothelial dysfunction in 9 patients with NRP. Endothelial function was assessed at baseline, after 12 weeks of atorvastatin treatment and after an 8 week wash‐out period. Brachial artery endothelial function was studied by measuring post‐ischaemic flow‐mediated dilatation (FMD) using ultrasonography. Endothelium‐ independent, glyceryl trinitrate (GTN) mediated vasodilatation was also measured. RESULTS: At baseline, median serum albumin was 31g/L (range 20‐40) and 24 hour protein excretion was 4.7g (1.0‐16.23). There was no significant change in serum creatinine and 24 hour protein excretion during the study. Total cholesterol (TC) and triglycerides (TG) were significantly lower following treatment with atorvastatin 20mg (20‐40): TC 8.1mmol/L (5.9‐14.9) vs. 5.2 (4.0‐8.6), TG 2.9mmol/L (1.3‐15.0) vs. 1.6 (1.0‐3.5), both p < 0.05. Brachial artery FMD improved significantly following atorvastatin treatment: 2.1% (‐1.2‐ 5.2%) to 4.7% (0.8‐16.3%), p < 0.05. At the end of the 8 week wash‐out, FMD had significantly deteriorated to 3.2% (‐2.8‐8.2), p < 0.05 vs. week 12 FMD, and was similar to pre‐treatment values. GTN mediated dilatation was unchanged through the study. CONCLUSION: Atorvastatin significantly reduced the hyperlipidaemia of NRP. This was associated with improved conduit artery endothelial function after 12 weeks of treatment. This is consistent with the hypothesis that dyslipoproteinaemia is the primary cause of endothelial dysfunction in NRP.     

兔肝癌组织缺血再灌注后的损伤及凋亡

目的研究肝癌缺血再灌注后的损伤及凋亡。方法超声引导穿刺新西兰兔肝脏左中叶注射VX2肿瘤组织混悬液,建立肝脏肿瘤模型,阻断肿瘤所在的肝左中叶的肝动脉分支60min后去除血管阻断恢复血流,分别再灌注0min、1h、1d、3d和1w。取肿瘤组织、癌周组织和肝脏组织,除测定肿瘤组织和肝脏组织超氧化物歧化酶(SOD)、丙二醛(MDA)的含量外,还对肿瘤组织、癌周组织及肝脏组织进行了HE染色。结果缺血再灌注后肿瘤组织和正常肝组织中的SOD浓度均迅速下降并分别于再灌注1h和0min达最低水平(64.59±4.97,12.38±0.31),其后逐渐恢复(112.83±5.84,25.78±0.56)但至再灌注7d仍低于再灌注前(200.32±26.43,42.00±1.07)。但癌组织中的SOD含量下降更为显著。从缺血再灌注开始至7d肿瘤组织的MDA含量下降(21.59±0.59),而肝脏组织缺血再灌注后0min至7d(29.04±1.43),MDA含量明显升高,均高于缺血再灌注前水平(18.26±0.43)。HE染色显示,肝癌组织缺血再灌注后凋亡细胞明显增多,其中以1d最为显著(23.08%),而癌周和肝组织改变不甚明显(与同时点的癌组织相比P<0.01)。结论缺血再灌注可增强对肝癌组织的损伤并促进细胞凋亡而癌周和正常肝脏组织的改变不明显。     

兔肝脏保存─再灌注损伤模型的建立及评价

作者应用导管将受体腹主动脉血液分流至供肝，建立了兔肝脏保存一再灌注损伤模型。并对再灌注前、后供肝及受体肝脏的组织结构及功能、再灌注后供肝血流量及受体血流动力学变化进行了动态观察。结果表明，该模型具有良好的稳定性及重复性，且能准确地反映肝移植时供肝保存一再灌注损伤的病理生理过程。     

PS10PHAEOCHROMOCYTOMA IN CHILDREN

Purpose Phaeochromocytomas are rare tumours of the sympathoadrenal neuroendocrine system. It is known that these tumours are associated with Von Hippel Lindau (VHL) disease, multiple endocrine neoplasia type II and neurofibromatosis type I. Recently an association with succinate dehydrogenase type B and D gene mutations has been described. Discovery of a SDHB mutation in a girl at our hospital prompted us to review our experience with phaeochromocytoma in children. Methodology Retrospective review of case notes of all children treated for phaeochromocytoma over the period 1997–2006 at Starship Children’s Hospital, NZ. Results Seven patients with 8 tumours were identified with average age of 10 years and average systolic BP of 161. The tumours were adrenal in location in 37.5% and 62.5% extra‐adrenal. Our malignancy rate was 12.5%. Familial disease was noted in two patients with one girl having VHL disease and the other found to carry a mutation in the SDHB gene. All children received preop antihypertensives and were treated operatively with seven open resections and one laparoscopic converted to open resection. One child received adjuvant radiotherapy. There were no recurrences or deaths. Conclusions Phaeochromocytoma in children varies from the adult form. It is more likely to be extra‐adrenal and have a greater chance of a familial genetic syndrome. The discovery of SDH mutations has altered the diagnosis of familial disease and carries implications for family screening, prognosis and surveillance. We emphasize the importance of taking a good family history and suggest screening for SDH mutations in all patients with phaeochromocytoma.     

盐酸氟桂利嗪对再灌注损伤时鼠肝细胞线粒体的作用

目的 盐酸氟桂利嗪对大鼠肝脏缺血／再灌注香肝细胞线粒体的影响。方法：将Ｗｉｓｔａｒ大鼠随机分为三组,每组１２只。Ａ组为对照组,Ｂ组缺血／再灌注组组,Ｃ组为盐酸氟桂利嗪组。其中Ｂ,Ｃ两组均阻断肝门造成肝脏完全缺血３０分钟后再灌注９０分钟。测定各组动物血清中ＡＬＴ,ＬＤＨ含量,肝细胞线粒体脂质过氧化物（ＬＰＯ）含量、行超微结构的观察。结果 与Ａ组比较,Ｂ组血清ＡＬＴ,ＬＤＨ活性显著加（Ａ,Ｂ二组,ＡＬ     

ML01COMPETENCE REVIEWS IN NEW ZEALAND AND THE AFTERMATH

The inquiry into allegations concerning the treatment of cervical cancer at National Womens Hospital in 1987 and 1988 was one of the most significant medical controversies of the 20th century in New Zealand. This event brought the legal and medical professions into close contact, and the legal profession has been involved with further developments in the assessment of medical competence. Since the inquiry in 1988 the government in New Zealand has moved to provide “further protection to the community”: The appointment of a Health and Disability Commissioner to act as an advocate for the community and changes in legislation. As a result, the self regulating privilege of the medical profession has been lost. The profession was initially stunned by the outcomes of the National Womens Review, but on the positive side there has been a response by the profession to improve the standards of practice. The department of Continuing Professional Development in the RACS has been a major step forward. Over the next two days the Medico‐Legal Section will examine our response to competence reviews. The changes over the last twenty years have brought about considerable change in our professional status within the community, but we must continue to address those matters which have resulted in a loss of community trust.     

FK409对大鼠肝脏移植缺血再灌注损伤后JAK2/STAT3信号通路的影响

目的 探讨FK409对人鼠肝脏移植缺血再灌注损伤后细胞凋亡及JAK2,STAT3表达的影响.方法雄性SD 大鼠60只,随机分为假于术组、牛理盐水干预组、FK409干预组,采用Kamada's袖套法建立大鼠原位肝移植模型.干预组于新肝开放前分别鼠尾静脉注射FK409 2 mg/kg或等量生理盐水,于24 h后RT-PCR及免疫组织化学方法检测JAK2,STAT3表达水平的变化;利用原位缺口未端标记法(TUNEL法)研究肝细胞凋亡的变化.结果 与生理盐水干预组相比,FK409干预组JAK2,STAT3表达明显减少(P＜0.05);凋亡细胞也减少(P＜0.05).结论 FK409尚能通过抑制与炎性细胞因子及氧化应激有密切关系的JAK2/STAT3信号转导通路显著减轻大鼠肝移植缺血再灌注损伤后组织损伤.     

一氧化氮,血栓素／前列环素及ATP与肝硬变大鼠肝脏缺血再灌注损伤

四氯化碳复制大鼠肝硬变模型，通过大鼠肝脏缺血再灌注损伤模型，比较硬变肝与正常肝在缺血再灌注损伤时的差异和意义。结果显示：肝硬变时对缺血再灌注损伤反应与正常大鼠不同，再灌注时肝脏一氧化氮合成释放显著增加，肝组织ＡＴＰ含量明显降低且长时间难以恢复等，可能是肝硬变时对缺血再灌注损伤更敏感、更易发生肝功能衰竭的重要原因。     

MORPHOLOGICAL ANALYSIS OF ILEAL GRAFTING FOLLOWING ILEOCYSTOPLASTY IN THE RAT: A KINETIC AND ULTRASTRUCTURAL STUDY OF THE INTESTINAL EPITHELIUM

lleocystoplasty was performed in rats and the morphological and cell-kinetic changes occurring in the ileal grafts were determined at intervals up to 18 months postoperatively. The intestinal mucosa underwent no progressive changes but included villous and avillous regions associated with crypts of various sizes at all time intervals. Newly appearing and densely packed epithelial cells, shaped like petals, were always present in the lower parts of the villi associated with crypts showing no elongation, but seldom present in those with elongated crypts in the villous mucosa. Bromodeoxyuridine studies showed that the petal-shaped cells interfered with cell migration. No petal-shaped cells were observed in avillous mucosa in which the rate of cell turnover depended on crypt size. Fine-structural changes in absorptive epithelial cells in both types of mucosa included features of prematurity or hypermaturity in the cytoplasm and close adherence to the basal portions of adjacent cells and to the basal lamina. These changes may possibly contribute to the prevention of reabsorption of urine. However, some of the mechanisms responsible for adherence of the basal parts might incidentally interfere with the normal cell kinetics of the intestinal epithelium, resulting in dense packing of cells and the formation of multiple types of mucosa in ileal grafts.     

HP01METALS IN GALLBLADDER CARCINOGENESIS

Carcinoma gallbladder is the commonest malignancy in the Northern part of India. The heavy metals are known carcinogens while trace metals have protective effect. Aim The aim of the study is to estimate the heavy and trace metal (Lead, Zinc, Copper, Cadmium, Chromium, Manganese and Selenium) concentration in serum, bile, tissue and gallstone in patients with gallbladder diseases. Method This is a pilot study conducted in 45 cases (Group – I: 15 cases of carcinoma gallbladder, Group II: 15 patients of cholecystitis with cholelithiasis and Group – III: 15 patients of healthy control), to detect the relationship between the heavy and trace metal concentration and gall bladder carcinoma. Analysis of metal was done using Perkins‐Elmer model 2380 atomic absorption spectrophotometer. Results The serum concentration of copper and nickel was significantly high in carcinoma gallbladder patients as compared to patients with cholecystitis while zinc and selenium is low in carcinoma gallbladder patients. Bile concentration of zinc, selenium and manganese was significantly low in carcinoma gallbladder patients (p < 0.05) as compared to patients of cholelithiasis while cadmium and nickel was high. Tissue concentration of manganese was significantly low in carcinoma gallbladder patients as compared to patients of cholelithiasis while chromium was high. Gallstone concentration of copper, manganese and lead was significantly low in carcinoma gallbladder patients as compared to patients of cholelithiasis. Conclusion The heavy metals are in higher concentration in carcinoma gallbladder while trace metals are in lower concentration indicating possible role of heavy metal in gallbladder carcinogenesis.     

rhGH在大鼠肝脏缺血再灌注损伤中保护和修复的作用

目的 探讨重组人生长激素（rhGH）在肝脏缺血再灌注损伤中的保护和修复作用及其机理。方法 Pringles法建立180只肝脏缺血再灌注损伤模型,随机分为：A、B、C、D四组。A组：rhGH预处理组（n=50）,B组：作为A组的对照组（n=50）;A组：建模前连续7d给予重组人生长激素（rhGH）针剂皮下注射0．2IU／100g（体重）／d,B组分别给予等量的生理盐水。观察ALT、TNF-α、1L-α、丙二醛（MDA）肝脏能荷（Energycharge,EC）的变化,电镜观察肝脏超微结构变化。C组：rhGH治疗组（n=40）,D组：作为C组的对照组（n=40）实验组建立模型后7d每天给予rhGH针剂皮下注射（0．2IU／100g）,对照组分别给予等量的生理盐水;检测ALT、TNF-α、IL-1αEC、电镜观察肝脏超微结构的变化。结果 A、B两组：A组ALT、TNF—a、、IL-1α和MDA在各个时间点的水平明显低于B组（P〈0．05）。A组EC水平明显高于B组（P〈0．05）;B组电镜下可见肝窦内皮细胞破坏,肝细胞线粒体结构改变,A组肝细胞超微结构明显改善。C、D两组：ALT、TNF-α、明显降低,在7d（和）或14dC组与D组有显著性差异;C组EC7d、14d明显高于D组（P〈0．05）;C组肝细胞超微结构较D组亦有明显改善。结论 rhGH可能通过抑制了细胞因子（TNF-α、IL-1α,进一步减少MDA的生成,从而减轻了这些因子对肝脏损伤,rhGH对肝脏缺血再灌注损伤具有保护和修复作用;可以在肝脏缺血再灌注损伤后促进线粒体功能恢复,改善肝细胞能量代谢状态;rhGH在肝脏缺血再灌注损伤过程中,具有促进肝脏再生的作用。