热蒸馏水加药物灌注治疗恶性胸腔积液临床研究

将72例恶性胸水患者随机分为治疗组与对照组,治疗组胸部上、下植入两根胸管,放尽胸液后与心泵相连,建立起与体循环隔离的胸腔体外循环,以蒸馏水为预充液加入40 mg顺铂,加热到44～45℃连续灌注80～100min,停机拔除上胸管,将下胸管接水封瓶。对照组仅行胸腔闭式引流+胸腔内注入顺铂。与对照组比较,治疗组总有效率明显升高,拔管时间明显缩短,1 a存活率明显增高。

肝动脉灌注栓塞治疗中晚期肝癌36例长期随访观察

目的探讨肝癌对介入治疗后长期随访观察进行研究．方法本组36例均属于中晚期不能手术切除的肝癌，其中男31例，女5例，年龄28岁～68岁．原发性肝癌34例，转移性肝癌2例．采用Seldinger氏法，经皮股动脉穿刺插管，做选择性肝动脉造影证实．治疗方法：灌注抗癌药物表阿霉素40mg～60mg、丝裂霉素30mg～40mg、卡铂150mg～300mg、栓塞剂为无水酒精5mL～8mL，碘化油10mL～15mL，明胶海绵颗粒20粒～40粒．结果本组36例中有32例均有不同程度的症状改善和肿块缩小．18例AFP转阴，全部病例均随访8a，其中失访4例，随访率90％．36例中有18例在治疗后8mo～14mo死亡，生存1a以上仅有14例，生存率38．9％，生存2a8例，生存率22．2％，生存8a以上5例，至今健在，8a生存率13．8％．结论肝动脉灌注栓塞术对中晚期肝癌是一种姑息治疗方法．肝动脉栓塞主要针对肿瘤血管，使肿瘤组织有不同程度缺血坏死，最后达到萎缩和消失，对正常肝组织细胞影响不大，对较大肝脏肿瘤行肝动脉栓塞时，应掌握一定的栓塞剂量，分期进行栓塞才能达到治愈目的．从而提高生存率，优于外科手术切除治疗．

肝动脉灌注栓塞术治疗老年人肝癌的术后副反应、并发症及其处理

目的主要提出肝动脉灌注栓塞术治疗老年人肝癌术后并发症及其处理方法．方法本组125例，其中男98例，女27例，年龄60岁～78岁．全部病例均按全国防治组制定肝癌诊断标准，采用Seldinger法，行肝动脉造影，然后再讲行肝动脉灌注及栓塞术治疗肝癌．结果副反应：①恶心、呕吐，发生率在42％，多在1d～2d出现，持续2d～4d左右，应给予吸氧、肌注甲氧氯普胺后可以缓解消失．②右上腹部疼痛，发生率在95％，给予镇痛方可缓解．③发热，发生率在98．2％，应给予消炎痛可以缓解，如体温过高，可以给予地塞米松10mg静脉滴注．并发症：①肝脓肿：本组5例，表现肿区剧烈疼痛，体温较高，应用大量抗生素保守治疗1wk后好转．一旦发生较大脓肿可以穿刺引流术，同时向内注入抗生素治疗．②上消化道出血：在选择插管时，将导管尽量插到病变附近（越过胃十二指肠动脉）．如有上消化道出血，应给予H受体拮抗剂以保护胃粘膜．③右侧胸腔积液：可以保守治疗就能达到吸收治愈．④油酯性肺炎：应给予适当抗生素治疗均可痊愈．⑤胆囊炎：其发生率在10％，本组发生一例，经应用抗生素后症状好转．⑥EPI心肌中毒：文献报道约2％～3％，本组发生一例，当时给予吸氧和保护心肌方面治疗后好转．

支气管动脉灌注化疗结合放疗治疗非小细胞肺癌16例临床分析

支气管动脉灌注化疗结合放疗治疗非小细胞肺癌１６例临床分析王武章１王子斌１张春燕２公维松２１９９３～１９９６年，我们应用支气管动脉灌注大剂量以顺铂为主的联合化疗药物（局部化疗），并结合放疗治疗非小细胞肺癌１６例，效果良好。现将结果报告如下。１临床资料１...

心脏手术中心肌保护的展望

心脏手术中心肌保护的展望王世端自１９５５年Ｍｅｌｒｏｓｅ首先使用心脏停跳液灌注行心脏手术中心肌保护以来，为了达到最佳效果，已发展了多种不同配方的停跳液和灌注技术，但至今为止，仍没有一种完美、通用的技术。本文对近几年来在心肌保护方面的进展，如心肌缺血的...

The effects of anisodamine and dobutamine on gut mucosal blood flow during gut ischemia/reperfusion

AIM: To determine if anisodamine is able to augment mucosal perfusion during gut I/R ischemia-reperfusion. METHODS: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted into the sac which was filled with saline. The superior mesenteric artery was occluded (SMAO)for 60 minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO, either 0.2 mg/kg of anisodmine or dobutamine was injected into the jejunal sac. Laser Doppler mucosal blood flow and regional PCO2 (PrCO2)measurements were made. RESULTS: Mucosal blood flow was significantly increased at 30,60 and 90 minutes of reperfusion (R30, R60, R90) when intraluminal anisodamine or dobutamine was present compared to intraluminal saline only(44+/-3.3% or 48+/-4.1% vs 37+/-2.6% at R30, 57+/-5.0% or 56+/-4.7% vs 45+/-2.7% at R60, 64+/-3.3% or 56+/-4.2% vs 48+/-3.4% at R90,respectively P【0.05). Blood flow changes were also reflected by lowering of jejunal PrCO2 measurements after intraluminal anisodamine or dobutamine compared with that of the saline controls (41+/-3.1 mmHg or 44+/-3.0 mmHg vs 49+/-3.7 mmHg at R30,38+/-3.7 mmHg or 40+/-2.1 mmHg vs 47+/-3.8 mmHg at R60,34+/-2.1 mmHg or 39+/-3.0 mmHg vs 46+/-3.4 mmHg at R90, respectively, P【0.05). Most interesting finding was that there were significantly higher mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in dobutamine group at 90 minutes of reperfusion(64+/-3.3% vs 56+/-4.2% for blood flow or 34+/-2.1 mmHg vs 39+/-3.0 mmHg for PrCO2, respectively, P【0.05), suggesting that anisodamine had a more lasting effect on mucosal perfusion than dobutamine. CONCLUSION: Intraluminal anisodamine and dobutamine can augment mucosal blood flow during gut I/R and alleviate mucosal acidosis. The results provided beneficial effects on the treatment of splanchnic hypoperfusion following traumatic or burn shock.

Interaction of L-Arginine-methyl ester and Sonic hedgehog in liver ischemia-reperfusion injury in the rats

AIM： To investigate the role of Sonic hedgehog （Shh） on the course of liver ischemia and reperfusion （I/R） in rats, and the interaction between treatment with nitric oxide donor L-Arginine-methyl ester （L-Arg） and up-regulation of Shh expression.METHODS： A total of 30 male Sprague-Dawley rats weighing 220-240 g were used in this study. Shamcontrol group （G1, n = 10）： a sham operation was performed （except for liver I/R）. I/R-untreated group （G2, n = 10）： rats underwent liver ischemia for 1 h followed by reperfusion for 45 min. I/R-L-Arg group （G3, n = 10）： after performing the same surgical procedure as in group 2, animals were treated with L-Arg. Liver tissues were taken for determination of malondialdehyde （MDA） levels, and biochemical and histological evaluations were made.RESULTS： Plasma alanine aminotransferase （ALT）, aspartate aminotransferase （AS-T）, lactate dehydrogenase （LDH） and T-glutamyltranspeptidase （GGT） activities were higher in group 2 than in group 3. MDA values and the hepatic injury score decreased in the L-Arg treated group compared to the I/R-untreated group. In group 2, the hepatoo/tes were swollen with marked vacuolization. Group 3 rats showed well-preserved liver parenchyma, with hepatocytes extending from the central vein. The morphology of the hepatocytes and the sinusoidal structures was normal, without any signs of congestion. Mild Shh positive immunostaining was detected in group 2 animals. The expression of immunoreactive cells was increased markedly in liver tissue from I/R-L-Arg rats.CONCLUSION： Our findings suggest that Shh molecules are critical factors in the pathophysiology of inflammatory liver injury induced by I/R. In addition, NO plays an important role in the immunohistochemical expression of these molecules.

New progress in roles of nitric oxide during hepatic ischemia reperfusion injury

Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1 alpha-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.

Organ preconditioning: the past, current status, and related lung studies

Preconditioning (PC) has emerged as a powerful method for experimentally and clinically attenuating various types of organ injuries. In this paper related clinical and basic research issues on organ preconditioning issues were systemically reviewed. Since lung injuries, including ischemia-reperfusion and others, play important roles in many clinical results, including throm-boembolism, trauma, thermal injury, hypovolemic and endotoxin shock, reimplantation response after organ transplantation, and many respiratory diseases in critical care. It is of interest to uncover methods, including the PCs, to protect the lung from the above injuries. However, related studies on pulmonary PC are relatively rare and still being developed, so we will review previous literature on experimental and clinical studies on pulmonary PC in the following paragraphs.

Protective effect of prednisolone on ischemia-induced liver injury in rats

AIM: To investigate the effects of prednisolone on cell membrane bleb formation, calpain μ activation and talin degradation during hepatic ischemia-reperfusion injury in rats. METHODS: The hilar area of the left lateral and median lobes of rat liver (68%) was clamped for 60 min and followed by 120 min reperfusion. Prednisolone was administered at 1.0, 3.0, or 10 mg/kg at 30 min before ischemia. In addition to biochemical and microscopic analyses, activation of calpain μ was determined using specific antibodies against the intermediate (activated) form of calpain μ. Degradation of talin was also studied by Western blotting. RESULTS: In the control and prednisolone (1.0 mg/kg) groups, serum aspartate transaminase (AST) and alanine transaminase (ALT) level were elevated, and cell membrane bleb formation was observed after 120 min of reperfusion. Moreover, calpain μ activation and talin degradation were detected. Infusion of prednisolone at 3.0 or 10 mg/kg significantly suppressed serum AST and ALT, and prevented cell membrane bleb formation. At 10 mg/kg, prednisolone markedly suppressed calpain μ activation and talin degradation. CONCLUSION: Prednisolone can suppress ischemia- reperfusion injury of the rat liver. Its cytoprotective effect is closely associated with the suppression of calpain μ activation and talin degradation.

Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

Objective： To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods： lschemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons （CGNs） by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation （OGD）. Results： The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential （its maximal protection ratio was 73.26%） and release of cytochrome c （its maximal inhibition ratio was 42.52%） and the subsequent activation of caspase-3 （its maximal protection ratio was 59.32%） in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion： Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfiusion.

INFLUENCE OF LOCAL INFILITRATION ANESTHESIA OF SCALP-POINT ON ACUPUNCTURE INDUCED CHANGES OF CEREBRAL BLOOD PERFUSION DETECTED BY SPECT

Objective: To observe the influence of local infiltration anesthesia at the scalp point on acupuncture stimulation induced changes of cerebral blood perfusion in the brain. Methods: Experiments were conducted in 10 healthy volunteer subjects (8 males and 2 females) who were ordered to take a lying position on a specific bed with their heads keeping in a fixed position. Scalp point used was Motor Area (MS 6). The first syringe needle (gauge 5) was inserted into the scalp from the upper 1/5 of MS 6 and the second syringe needle inserted into the scalp from the middle 2/5 of MS 6 and advanced downward, with the two needles connected to a HAN’s Therapeutic Apparatus. Images of the brain were then taken before and after electroacupuncture (EA) stimulation, and after local injection of 1% lidocaine [mixed with epinephrine (1∶200,000, 3 mL)] plus EA by using Siemens ECAM/ICON Single Photo Emission Computed Tomography (SPECT). Intravenous injection of Ethyl cysteinate dimmer 555 MBq was performed before displaying cerebral images. Data of blood functional changing rat (BFCR%) were analyzed quantitatively using a mathematic model. Results: Before EA stimulation, the blood perfusion and function of cerebral cortex, thalamus, basal ganglion and cerebellum on both sides of the brain were basically symmetry. Following EA of MS 6, BFCR% of the contralateral thalamus, parietal lobe and the frontal lobe increased significantly. Following local infiltration anesthesia, BFCR% of the contralatral thalamus declined markedly (P<0.05). The results of quantitative analysis were in agreement with those of visual observation. Conclusion: Local infiltration anesthesia of the scalp point can significantly weaken or block EA stimulation induced changes of BFCR%.

Intestinal microflora in rats with ischemia/reperfusion liver injury

Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.

CHANGES OF ENDOTHELIN－1 GENE EXPRESSION IN RAT BRAINS DURING ISCHEMIA AND ISCHEMIC REPERFUSION

Objective. The experiment was designed to study the association of cerebral ischemia and reperfusion with endothelin- 1 (ET- 1) gene expression of rat brains and time-dependent changes of ET- 1 gene expression during cerebral ischemia.Materials and methods. Thirty- three male SD rats were divided into dot blot hybridization(n = 27) and in silu hybridization groups(n= 6). The focal cerebral ischemia and reperfusion models were made with suture embolism of middle cerebral artery. Dot blot hybridization groups were redivided into control and ischemic subgroups (ischemia for 0. 5 , 1 , 1. 5 , 3 , 6 , 12 , 24 , 48 and 72 h respectively). In situ hybridization groups were redivided into ischemia and reperfusion groups. After 24 h ischemia and 24 h reperfusion,ET1 gene expressions were investigated with in situ hybridization and the resuhs were analyzed with IBAS 2000 Image Analysis System.Results. Dot blot hybridization showed that ET-1 mRNA of cerebral cortex and caudate- putamen was increased at 6 h of ischemia and reached peak at 24 h (3. 9 and 3. 7 fold respectively) ,and at 72 h of ischemia it remained at high levels(3. 5 and 2. 1 fold respectively). In silu hybridization showed that the levels of ET- 1 mRNA of cerebral cortex and caudate-putamen were also markedly increased both in 24 h ischemia and 24 h reperfusion groups (P<0. 01 , P<0. 05 respectively) .Conclusions. ET-1 gene expression in focal ischemic brain tissue were markedly and progressively increased during cerebral ischemia and reperfusion and downregulation of ET- 1 gene expression may be a new approach to the treatment of ischemic cerebrovascular diseases.

Heme oxygenase-1 alleviates ischemia/reperfusion injury in aged liver

AIM: To investigate if ischemia/reperfusion (I/R) injury in aged liver could be alleviated by heme oxygenase-1 (HO-1).METHODS: Three groups of SD rats (16 mo old) were studied. Group 1: control donors received physiological saline 24 h before their livers were harvested; group 2: donors were pretreated with hemih 24 h before their livers were harvested; and group 3: donors received hemin 24 h before their livers were harvested and zinc protoporphyrin (ZnPP,HO-1 inhibitor) was given to recipients at reperfusion. The harvested livers were stored in University of Wisconsin solution (4 ℃) for 6 h, and then transplanted to syngeneic rats. Serum glutamic oxaloacetic transaminase (SGOT),apoptotic cells, and apoptotic gene were measured 3, 6,12, 24, 48 h after reperfusion. We measured the apoptotic index by TUNEL, determined the expression of antiapoptotic Bcl-2 and proapoptotic (caspase-3) gene products by Western blot.RESULTS: After 3, 6, 12, 24, and 48 h of reperfusion, the SGOT levels (584.4±85.8 u/L, 999.2±125.2 u/L, 423.4±161.3u/L, 257.8±95.8 u/L, and 122.4±26.4 u/L) in hemin group were significantly (all P＜0.05) lower than those in saline group (1082.2±101.2 u/L, 1775.2±328.3 u/L, 840.4±137.8 u/L,448.6±74.3 u/L, and 306.2±49.3 u/L). Liver HO-1 enzymatic activity correlated with beneficial effects of hemin and deleterious effects of adjunctive ZnPP treatment. Markedly less apoptotic (TUNEL+) liver cells 3, 6, 12, 24, and 48 h after reperfusion (5.16±0.73, 10.2±0.67, 9.28±0.78, 7.14±1.12,and 4.78±0.65) (P＜0.05) could be detected in hemin liver grafts, as compared to controls (7.82±1.05, 15.94±1.82,11.67±1.59, 8.28±1.09, and 6.36±0.67). We detected the increased levels of Bcl-2 (1.5-fold) expression and compared with saline controls. These differences were most pronounced at 12 h after transplantation. In contrast, an active form of proapoptotic caspase-3 (p20) protein was found to be 2.9-fold lower at 24 h in hemin-pretreated group, as compared to saline liver transplant controls.CONCLUSION: HO-1 overexpression can provide potent protection against cold I/R injury. This effect depends, at least in part, on HO-1-mediated inhibition of antiapoptotic mechanism.

Relevance of proteolysis and proteasome activation in fatty liver graft preservation: An Institut Georges Lopez-1 vs University of Wisconsin appraisal

To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions.METHODSFatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to “ex vivo” normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPS: measured as chymotryptic-like activity and 20S and 19S proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3).RESULTSProfiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (P < 0.05) after cold ischemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPS activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPS activation correlated with the prevention of liver injury (AST/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 levels.CONCLUSIONOur comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a higher UPS inhibition and reduced liver proteolysis.

Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically

AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.

Inhibition of p38 mitogen-activated protein kinase may decrease intestinal epithelial cell apoptosis and improve intestinal epithelial barrier function after ischemia- reperf usion injury

AIM: To investigate the role of p38 mitogen-activated protein kinase in rat small intestine after ischemia-reperfusion (I/R)insult and the relationship between activation of p38 MAPK and apoptotic cell death of intestine.METHODS: Ninety Wistar rats were divided randomly into three groups, namely sham-operated group (C), I/R vehicle group (R) and SB203580 pre-treated group(S).In groups R and S, the superior mesenteric artery(SMA)was separated and occluded for 45 min, then released for reperfusion for0.25, 0.5, 1, 2, 6, 12 and 24 h. In group C, SMA was separated without occlusion. Plasma D-lactate levels were examined and histological changes were observed under a light microscope. The activity of p38 MAPK was determined by Western immunoblotting and apoptotic cells were detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUDP-biotin nick end labeling (TUNEL).RESULTS: Intestinal ischemia followed by reperfusion activated p38 MAPK, and the maximal level of activation (7.3-fold vs sham-operated group) was reached 30 min after I/R. Treatment with SB 203580, a p38 MAPK inhibitor,reduced intestinal apoptosis (26.72±3.39% vs62.50±3.08%in I/R vehicle, P＜0.01) and decreased plasma D-lactate level (0.78±0.15 mmol/L in I/R vehicle vs0.42±0.17 mmol/L in SB-treated group) and improved post-ischemic intestinal histological damage.CONCLUSION: p38 MAPK plays a crucial role in the signal transduction pathway mediating post-ischemic intestinal apoptosis, and inhibition of p38 MAPK may attenuate ischemia-reperfusion injury.