肝移植后丝裂素活化蛋白激酶级联途径与肝细胞抗应激反应

目的 探讨肝脏移植后丝裂素活化蛋白激酶（MAPK）级联途径与抗应激反应的变化。方法 根据组织病理表现将肝脏标本分为正常肝对照组（A组），移植肝无排斥反应组（B组）和移植肝急性排斥反应组（C组），每例标本行MAPK，Ras,Jun及热休克蛋白70（HSP70蛋白）检测和RasmRNA及HSP70mRNA表达水平检测。结果 MAPK，Ras及Jun蛋白表达在A、B、C组依次增高，HSP70蛋白表达在B组最高，C组较B组有下降；RasmRNA和HSP70mRNA的表达与相应蛋白表达呈现同步性。结论 肝移植后肝细胞MAPK级联途径与抗应激反应发生变化。体现出肝细胞自我修复和保护效应，这种精细的调节机制对维持个体存活有积极意义。     

Combined treatment with cytoprotective agents and radiotherapy

Radiotherapy is associated with several toxicities affecting healthy tissues. One of the strategies aimed at decreasing radiation toxicity is the use of radioprotective agents, such as amifostine and palifermin, or factors stimulating hemopoetic stem cells (colony stimulating factors, CSFs): granulocyte-CSF, granulocyte macrophage-CSF and recombinant erythropoetins. The potential beneficial effect of these substances demonstrated in preclinical in vitro and in vivo studies led to numerous clinical trials. This review addresses the current experience on the use of cytoprotective agents in combination with radiotherapy, with particular focus on the safety of these approaches. Despite a relatively large body of literature data, the role of cytoprotective agents combined with radiotherapy remains controversial. Overall, their use in this application is still limited due to modest radioprotective effect for normal tissues, potential risk of tumor protection and increased treatment toxicity. The use of erythropoetins in combination with radiotherapy should generally be discouraged, whereas the safe and effective application of other agents warrants further investigations.     

DRDE-07 and its analogues as promising cytoprotectants to nitrogen mustard (HN-2)—An alkylating anticancer and chemical warfare agent

Nitrogen mustard (HN-2), also known as mechlorethamine, is an alkylating anticancer agent as well as blister inducing chemical warfare agent. We evaluated the cytoprotective efficacy of amifostine, DRDE-07 and their analogues, and other antidotes of mustard agents against HN-2. Administration of 1 LD₅₀ of HN-2 (20 mg/kg) percutaneously, decreased WBC count from 24 h onwards. Liver glutathione (GSH) level decreased prominently and the maximum depletion was observed on 7th day post-HN-2 administration. Oxidised glutathione (GSSG) level increased significantly at 24 h post-administration and subsequently showed a progressive decrease. Hepatic malondialdehyde (MDA) level and percent DNA damage increased progressively following HN-2 administration. The spleen weight decreased progressively and reached a minimum on 3–4 days with subsequent increase. The antidotes were administered repeatedly for 4 and 8 days after percutaneous administration of single sublethal dose (0.5 and 0.25 LD₅₀) of HN-2. Treatment with DRDE-07, DRDE-30 and DRDE-35 significantly protected the changes in spleen weight, WBC count, GSH, GSSG, MDA and DNA damage following HN-2 administration (0.5 and 0.25 LD₅₀). There was no alteration in the transaminases (AST and ALT), and alkaline phosphatase (ALP) activities, neither with HN-2 nor with antidotes. The present study shows that HN-2 is highly toxic by percutaneous route and DRDE-07, DRDE-30 and DRDE-35 can partially protect it.     

Gastric mucosal phospholipids in dogs with familial stomatocytosis−hypertrophic gastritis

In dogs, hypertrophic gastritis, which resembles Ménétrier's disease in man, has been demonstrated to be part of a hereditary syndrome called familial stomatocytosis–hypertrophic gastritis. In addition to hypertrophic gastritis, affected dogs exhibit abnormal blood phospholipid composition. Phospholipids may play a role in maintaining gastric mucosal integrity, and this may be compromised in gastritis. The question arises whether the differences in blood phospholipids may result from a disorder that might also be revealed in the composition of gastric mucosal phospholipids. We analysed the phospholipid composition of gastric mucosa from four dogs with familial stomatocytosis–hypertrophic gastritis. The general phospholipid composition and the molecular composition of phosphatidylcholine from mucosal tissue in the corpus of the stomach where hypertrophic gastritis was evident were not different from that of the antrum, where the tissue was normal. These results do not corroborate a relation between the gastric mucosal phospholipid composition and hypertrophic gastritis.     

党参及其有效成分抗胃粘膜损伤作用与机制研究——Ⅲ、党参部位Ⅶ中的分离物抗胃粘膜损伤作用观察

用三种不同工艺流程均可从党参部位Ⅶ中得到抗大鼠胃粘膜损伤的有效分离物,从而进一步说明党参部位Ⅶ是党参抗胃粘膜损伤的有效部位,值得进一步研究。     

肺动脉灌注低温肺保护液抑制肺内实质细胞凋亡的研究

目的　探讨体外循环中肺动脉灌注低温保护液对肺内实质细胞凋亡的影响。方法　将4 0例行法洛四联症根治术的患儿分为肺保护组和对照组 (各 2 0例 )。肺保护组体外循环期间肺动脉灌注低温肺保护液 ,对照组行常规法洛四联症根治术。 2 0例患儿 (两组各 10例 )术后取右下肺组织活检标本 ,原位末端标记免疫组化染色法检测肺内实质细胞凋亡情况。同时监测围手术期肺功能及临床指标。结果　肺保护组肺内实质细胞凋亡率为 (10± 2 ) % ,而对照组肺内实质细胞凋亡率为 (18± 7) % ,两者比较 ,差异有显著性 (t=- 2 95 ,P <0 0 5 )。肺保护组术后氧指数较对照组高 ,回ICU病房后 0、6和 12h均有显著差异 [分别为 (4 92± 172 )、(4 4 4± 10 4 )、(4 89± 5 8)mmHg和 (36 9± 12 6 )、(347± 10 7)、(340± 119)mmHg ,t =2 5 9,P <0 0 5 ;t=2 88,P <0 0 1;t =5 0 6 ,P <0 0 1];肺保护组呼吸机辅助通气时间短于对照组 [(15± 11)h和 (2 6± 15 )h ,t=- 2 76 ,P <0 0 1]。结论　肺动脉灌注低温保护液可抑制肺组织内实质细胞凋亡 ,减轻体外循环肺损伤     

经上腔静脉逆行灌注脑保护在主动脉瘤手术中的应用

目的　探讨在主动脉瘤手术中应用经上腔静脉逆行灌注的脑保护效果。　方法　 65例主动脉瘤患者分 2组 ,15例采用深低温停循环 (DHCA) ,5 0例经上腔静脉逆行灌注 (RCP)进行脑保护。术中比较 2组患者不同时间颈内静脉的血乳酸含量 ,对部分RCP患者测定了灌注血和回流血的流量分布 ,以及灌注血和回流血的氧含量。　结果　DHCA组停循环时间为 10 0～ 63 0min ,平均(3 5 9± 18 8)min ;RCP组为 16 0～ 81 0min ,平均 (45 5± 17 2 )min。术后至清醒时间DHCA组为4 4～ 9 4h ,平均 (7 1± 1 6)h ;RCP组 2 0～ 9 0h ,平均 (5 4± 2 2 )h。DHCA组手术死亡 3例 ,RCP组死亡 1例 ;术后神经系统并发症DHCA组 3例 (死亡 2例 ,成活 1例 ) ,RCP组 1例 (存活 )。手术总成功率和神经系统并发症发生率RCP组分别为 96%和 2 % ,DHCA组为 67%和 2 0 % (P <0 0 5 )。RCP组再灌注期间颈内静脉血乳酸含量增高幅度低于DHCA组 [(4 4± 0 6)mmol/Lvs (6 2± 0 9)mmol/L ,P <0 0 1],经头臂和下腔静脉血流量测定显示约 2 0 %血液经头臂动脉回流 ,灌注血和回流血氧差9 0 0～ 13 67ml/L ,证实RCP期间脑组织有氧利用。　结论　在主动脉瘤手术中 ,应用RCP可以延长停循环的安全时限 ,是可行的脑保护方法     

Roles of cyclooxygenase-2 and prostaglandin E receptors in gastric mucosal defense in <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-infected mice

Background/Aim: Helicobacter pylori (H. pylori) induces cyclooxygenase-2 (COX-2) expression. The aim of this study was to assess the roles of COX-2 and PGE₂ receptors (EPs) in gastric defense in H. pylori-infected mice. Methods: Gastric lesions were induced by oral administration of 0.15 N HCl in 60 % ethanol (HCl/EtOH) to mice infected with H. pylori, and macroscopically evaluated 30 min later. Mice were administered NS-398 (COX-2 selective inhibitor) concomitantly with selective EP agonists 4 hours before HCl/EtOH challenge. Results: H. pylori infection prevented the gastric damage induced by HCl/EtOH, and this protective effect was abolished by NS-398. Selective agonists of EP1, EP2, and EP4, but not the EP3 agonist, reversed the inhibitory effect of NS-398 on prevention of damage by H. pylori infection. The EP4 agonist and EP2/EP4 agonists inhibited the increase in TNF-α mRNA expression and neutrophilic infiltration caused by NS-398, respectively. Conclusion: COX-2-derived PGE₂ may play an important role in resistance to HCl/EtOH damage in H. pylori-infected mice by activating EP1, EP2, and EP4. Received 1 August 2006; accepted 21 August 2006     

新生鼠肠道缺乏适应性细胞保护

目的探讨新生大鼠肠道是否存在适应性细胞保护作用。方法新生大鼠称重后随机分到各组,分别予生理盐水(NS)、生理盐水 盐酸(NS HCl)、盐酸(HCl)、醋酸1(AA1)灌肠作预处理,30min后再给予醋酸(AA)灌肠(另设一组用NS作预处理,30min后再予NS灌肠);24h后称重,然后断颈处死;取出近端结肠用以组织病理学评分,并留取血清标本做髓过氧化物酶(MPO)活性检测和白细胞介素6(IL-6)浓度检测。结果(NS HCl) AA、HCl AA、AA1 AA各组与NS AA组比较,组织病理学评分、髓过氧化物酶活性、血清白细胞介素6(IL-6)浓度各方面反而增加,P>0.05;试验前后24h体重增长反而较少,P>0.05。(NS HCl) AA、HCl AA、AA1 AA各组与NS NS组比较,组织病理学评分、髓过氧化物酶活性、血清白细胞介素6(IL-6)浓度各方面明显增加,P<0.05;试验前后24h体重增长明显减少,P<0.05。结论新生鼠的肠道缺乏适应性细胞保护作用。     

Expression of the inducible nitric oxide synthase in distinct cellular types after traumatic brain injury: an in situ hybridization and immunocytochemical study

The Marmarou’s acceleration traumatic brain injury (TBI) model, in situ hybridization and immunocytochemistry were utilized to study the temporal expression of the inducible form of nitric oxide synthase (iNOS) mRNA and protein in different cellular compartments of the rat brain. Four hours following TBI, expression of iNOS was observed in the endothelial cells of cerebral blood vessels, macrophages and many cortical and hippocampal neurons. In the cortex labeled neuronal and non-neuronal cells were primarily found in the superficial layers. In the hippocampus the strongest neuronal labeling was observed in the CA1 and CA3 (lateral part) regions. By 24 h post TBI endothelial cells no longer expressed iNOS mRNA, and the macrophage and neuronal iNOS expression was reduced by 30–50%. The reduction was assessed by automated quantitation of the silver grains that occupy individual cellular profiles using an image analysis system. Immunocytochemistry revealed de novo iNOS synthesis in non-neuronal cells at the different time points, thus paralleling the changes in iNOS mRNA expression. In contrast, iNOS immunoreactivity in neurons was not observed before 24 h post TBI, suggesting failure of iNOS protein translation at 4 h after trauma. The results demonstrate complex spatial and temporal patterns of iNOS expression in discrete cellular populations, indicating different times of nitric oxide synthesis (and release) following TBI. Uncoupling of iNOS mRNA and protein synthesis in neurons suggests differential synthesis of nitric oxide in these cells as compared to non-neuronal cellular populations after trauma. Received: 27 July 1999 / Revised: 4 October 1999 / Accepted: 3 November 1999