Effect of nuclear factor kappa B on intercellular adhesionrnolecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats

AIM: To investigate the role of nuclear factor kappa B(NF-κB) in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R), and its effect on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration.METHODS: Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate (PDTC) treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery (SMA) occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid (BALF) protein were assayed. Serum IL-6, lung malondialdehyde (MDA) and myeloperoxidase (MPO) as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS: Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group (P=0.001). Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly(P＜ 0.05) when compared to I/R group.CONCLUSION: The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.     

Nuclear factor-kappaB decoy oligodeoxynucleotides attenuates ischemia/reperfusion injury in rat liver graft

AIM: To evaluate the protective effect of NF-kappaB decoy oligodeoxynucleotides (ODNs) on ischemia/reperfusion (I/R) injury in rat liver graft. METHODS: Orthotopic syngeneic rat liver transplantation was performed with 3 h of cold preservation of liver graft in University of Wisconsin solution containing phosphorothioated double-stranded NF-kappaB decoy ODNs or scrambled ODNs. NF-kappaB decoy ODNs or scrambled ODNs were injected intravenously into donor and recipient rats 6 and 1 h before operation, respectively. Recipients were killed 0 to 16 h after liver graft reperfusion. NF-kappaB activity in the liver graft was analyzed by electrophoretic mobility shift assay (EMSA). Hepatic mRNA expression of TNF-alpha, IFN-gamma and intercellular adhesion molecule-1 (ICAM-1) were determined by semiquantitative RT-PCR. Serum levels of TNF-alpha and IFN-gamma were measured by enzyme-linked immunosorbent assays (ELISA). Serum level of alanine transaminase (ALT) was measured using a diagnostic kit. Liver graft myeloperoxidase (MPO) content was assessed. RESULTS: NF-kappaB activation in liver graft was induced in a time-dependent manner, and NF-kappaB remained activated for 16 h after graft reperfusion. NF-kappaB activation in liver graft was significant at 2 to 8 h and slightly decreased at 16 h after graft reperfusion. Administration of NF-kappaB decoy ODNs significantly suppressed NF-kappaB activation as well as mRNA expression of TNF-alpha, IFN-gamma and ICAM-1 in the liver graft. The hepatic NF-kappaB DNA binding activity [presented as integral optical density (IOD) value] in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (2.16+/-0.78 vs 36.78+/-6.35 and 3.06+/-0.84 vs 47.62+/- 8.71 for IOD value after 4 and 8 h of reperfusion, respectively, P<0.001). The hepatic mRNA expression level of TNF-alpha, IFN-gamma and ICAM-1 [presented as percent of beta-actin mRNA (%)] in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (8.31+/-3.48 vs 46.37+/-10.65 and 7.46+/- 3.72 vs 74.82+/-12.25 for hepatic TNF-alpha mRNA, 5.58+/-2.16 vs 50.46+/-9.35 and 6.47+/-2.53 vs 69.72+/-13.41 for hepatic IFN-gamma mRNA, 6.79+/-2.83 vs 46.23+/-8.74 and 5.28+/-2.46 vs 67.44+/-10.12 for hepatic ICAM-1 mRNA expression after 4 and 8 h of reperfusion, respectively, P<0.001). Administration of NF-kappaB decoy ODNs almost completely abolished the increase of serum level of TNF-alpha and IFN-gamma induced by hepatic ischemia/reperfusion, the serum level (pg/mL) of TNF-alpha and IFN-gamma in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (42.7+/-13.6 vs 176.7+/-15.8 and 48.4+/-15.1 vs 216.8+/-17.6 for TNF-alpha level, 31.5+/-12.1 vs 102.1+/-14.5 and 40.2+/-13.5 vs 118.6+/-16.7 for IFN-gamma level after 4 and 8 h of reperfusion, respectively, P<0.001). Liver graft neutrophil recruitment indicated by MPO content and hepatocellular injury indicated by serum ALT level were significantly reduced by NF-kappaB decoy ODNs, the hepatic MPO content (A655) and serum ALT level (IU/L) in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the I/R group rat (0.17+/-0.07 vs 1.12+/-0.25 and 0.46+/-0.17 vs 1.46+/-0.32 for hepatic MPO content, 71.7+/-33.2 vs 286.1+/-49.6 and 84.3+/-39.7 vs 467.8+/-62.3 for ALT level after 4 and 8 h of reperfusion, respectively, P<0.001). CONCLUSION: The data suggest that NF-kappaB decoy ODNs protects against I/R injury in liver graft by suppressing NF-kappaB activation and subsequent expression of proinflammatory mediators.     

心肌缺血/再灌注损伤后的肺组织损伤

目的初步探讨心肌缺血／再灌注损伤对肺组织损伤的可能机制。方法选取雄性成年SD大鼠（4～6月龄）,体重130～160g,建立成年大鼠缺血／再灌注模型。运用CK和MPO试剂盒检测肌酸激酶（CK）和髓过氧化物酶（MPO）的含量,运用双抗体夹心ABC—ELISA法检测细胞间黏附分子-1（ICAM-1）的含量。结果与伪手术组相比,缺血／再灌注大鼠的AN／AAR比值明显增高（P〈0．05）,CK在心肌缺血／再灌注大鼠血清中的含量明显升高（P〈0．05）,MPO与ICAM-1在心肌缺血／再灌注组大鼠血清和肺组织中含量明显升高（P〈0．05）。结论大鼠心肌缺血再灌注损伤后肺组织受到一定的损伤,可能与体循环中炎性介质的作用及肺组织的炎性应激有关。     

Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats

AIM: Nuclear factor kappa B (NF-κB) regulates a large number of genes involved in the inflammatory response to critical illnesses, but it is not known if and how NF-KB is activated and intercellular adhesion molecule-1 (ICAM-1) expressed in the gut following traumatic brain injury (TBI). The aim of current study was to investigate the temporal pattern of intestinal NF-κB activation and ICAM-1 expression following TBI. METHODS: Male Wistar rats were randomly divided into six groups (6 rats in each group) including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on d 7. Parietal brain contusion was adopted using weight-dropping method. All rats were decapitated at corresponding time point and mid-jejunum samples were taken. NF-KB binding activity in jejunal tissue was measured using EMSA. Immunohistochemistry was used for detection of ICAM-1 expression in jejunal samples. RESULTS: There was a very low NF-κB binding activity and little ICAM-1 expression in the gut of control rats after sham surgery. NF-KB binding activity in jejunum significantly increased by 160% at 3 h following TBI (P<0.05 vs control), peaked at 72 h (500% increase) and remained elevated on d 7 post-injury by 390% increase. Compared to controls, ICAM-1 was significantly up-regulated on the endothelia of microvessels in villous interstitium and lamina propria by 24 h following TBI and maximally expressed at 72 h post-injury (P<0.001). The endothelial ICAM-1 immunoreactivity in jejunal mucosa still remained strong on d 7 post-injury. The peak of NF-κB activation and endothelial ICAM-1 expression coincided in time with the period during which secondary mucosal injury of the gut was also at their culmination following TBI. CONCLUSION: TBI could induce an immediate and persistent up-regulation of NF-κB activity and subsequent up-regulation of ICAM-1 expression in the intestine. Inflammatory response mediated by increased NF-κB activation and ICAM-1 expression may play an important role in the pathogenesis of acute gut mucosal injury following TBI.     

Fish oil alleviates liver injury induced by intestinal ischemia/reperfusion via AMPK/SIRT-1/autophagy pathway

AIM To evaluate whether fish oil(FO) can protect liver injury induced by intestinal ischemia/reperfusion(I/R) via the AMPK/SIRT-1/autophagy pathway.METHODS Ischemia in wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO emulsion or normal saline was administered by intraperitoneal injection for 5 consecutive days to each animal. Animals were sacrificed at the end of reperfusion. Blood andtissue samples were collected for analyses. AMPK, SIRT-1, and Beclin-1 expression was determined in lipopolysaccharide(LPS)-stimulated HepG2 cells with or without FO emulsion treatment.RESULTS Intestinal I/R induced significant liver morphological changes and increased serum alanine aminotransferase and aspartate aminotransferase levels. Expression of p-AMPK/AMPK, SIRT-1, and autophagy markers was decreased whereas tumor necrosis factor-α(TNF-α) and malonaldehyde(MDA) were increased. FO emulsion blocked the changes of the above indicators effectively. Besides, in LPS-stimulated HepG2 cells, small interfering RNA(siRNA) targeting AMPK impaired the FO induced increase of p-AMPK, SIRT-1, and Beclin-1 and decrease of TNF-α and MDA. SIRT-1 siRNA impaired the increase of SIRT-1 and Beclin-1 and the decrease of TNF-α and MDA.CONCLUSION Our study indicates that FO may protect the liver against intestinal I/R induced injury through the AMPK/SIRT-1/autophagy pathway.     

Cardioprotective effects of Guanxinshutong (GXST) against myocardial ischemia/ reperfusion injury in rats

Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong (GXST), a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion (MI/R) injury in rats and explore its possible mechanism. Methods Forty-five male Sprague Dawley rats were randomized into three groups: non-MI/R group (Sham, n = 15), MI/R group treated with vehicle (Control, n = 15) and MI/R group treated with GXST (Drug, n = 15). MI/R was induced by ligation of the left anterior descending coronary artery (LAD) for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder (in the Drug group) or saline (in the Control and Sham groups) were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery (10 rats each group) after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. Results GXST significantly decreased levels of TNF-α, IL-1β, IL-6, ICAM-1, apoptosis index (AI) and infarct size. GXST also obviously inhibited nuclear factor kappa B (NF-κB) activity when compared with the Control group (all P < 0.05). Conclusions GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.     

ICAM-1表达在大鼠重症急性胰腺炎肺损伤中的作用

目的研究大鼠重症急性胰腺炎(SAP)肺组织细胞间粘附分子-1(ICAM-1)的表达与肺损伤的关系。方法将30只SD大鼠随机分为假手术组、SAP不同时间点(1 h、4 h、8 h和12 h)各组,用逆行胰胆管注射方法制备SAP模型。采用Western Blot法检测大鼠肺组织中ICAM-1蛋白表达,同时观察肺组织髓过氧化物酶(MPO)及病理改变。结果造模SAP 1 h后大鼠肺组织中ICAM-1的表达水平即比假手术组高(P<0.05),并持续升高达12 h,同时伴有MPO水平升高和肺组织病理损害的加重, ICAM-1表达与肺损伤程度、MPO水平之间以及肺组织MPO水平与与肺损伤程度均呈正相关,相关系数分别为0.88、0.91及0.86(P<0.01)。结论SAP大鼠肺组织中ICAM-1呈过度表达,ICAM-1表达的高低与肺损伤严重程度有关。肺组织中ICAM-1过度表达及中性粒细胞浸润是SAP肺损害发生的原因之一。     

Ischemic post-conditioning to counteract intestinal ischemia/reperfusion injury

Intestinal ischemia is a severe disorder with a variety of causes. Reperfusion is a common occurrence during treatment of acute intestinal ischemia but the injury resulting from ischemia/reperfusion (IR) may lead to even more serious complications from intestinal atrophy to multiple organ failure and death. The susceptibility of the intestine to IR-induced injury (IRI) appears from various experimental studies and clinical settings such as cardiac and major vascular surgery and organ transplantation. Whereas oxygen free radicals, activation of leukocytes, failure of microvascular perfusion, cellular acidosis and disturbance of intracellular homeostasis have been implicated as important factors in the pathogenesis of intestinal IRI, the mechanisms underlying this disorder are not well known. To date, increasing attention is being paid in animal studies to potential pre- and post-ischemia treatments that protect against intestinal IRI such as drug interference with IR-induced apoptosis and inflammation processes and ischemic pre-conditioning. However, better insight is needed into the molecular and cellular events associated with reperfusion-induced damage to develop effective clinical protection protocols to combat this disorder. In this respect, the use of ischemic post-conditioning in combination with experimentally prolonged acidosis blocking deleterious reperfusion actions may turn out to have particular clinical relevance.     

NF-κB对肠缺血再灌注肝损伤P-选择素表达和中性粒细胞浸润的作用

目的:探讨核转移因子-κB(NF-κB)在肠缺血再灌注肝损伤发病机制中的作用及其对P-选择素(P-selectin)表达和中性粒细胞浸润的影响．方法:Wistar大鼠24只随机分成对照(Control 组)、肠缺血再灌注(I／R组)和脯氨酸二硫代氨基甲酸酯(PDTC)治疗组(PDTC组),每组8只．I／ R和PDTC组大鼠行肠系膜上动脉夹闭1 h再灌注2 h．PDTC组于手术前1 h给予20 g／L PDTC 100 mg／kg ip．观察肝组织病理学及其肝功能变化,检测血清IL-6,肝组织匀浆超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)水平．免疫组化法观察肝组织P-selectin和NF-κB表达并采用Western blot法检测肝NF-κB的水平．结果:肠缺血再灌注诱发了肝损伤,表现为肝水肿、出血和炎性粒细胞浸润．与对照组相比,I／R组血清ALT、AST、IL-6水平明显升高 (143．16±53．02至192．31±42．09 U／L,P<0．05; 387．46±78．74至507．56±96．26 U／L,P<0．01; 22．51±6．10至42．85±7．35 ng／L,P<0．01)．肝组织SOD活性降低、MPO含量明显升高(244．87 ±25．11至173．21±16．60 U／mgprot,P<0．01; 2．36±0．56至4.32±0．77 U／g,P<0．01);肝组织的P-selectin和NF-κB表达增强．采用PDTC 预处理,与I／R组相比,肝损伤程度减轻,血清ALT(128．63±38．94 U／L)、AST(462．86± 60．84 U／L)以及IL-6(28．08±7．55 ng／L)水平明显降低(P<0．01,P<0．05,P<0．05);肝脏氧化损伤及白细胞浸润减弱,表现为肝组织SOD活性升高(253．45±25．21 U／mgprot,P<0．01)、MPO 含量降低(3．58±0．49 U／g,P<0．05),同时伴有肝组织中的P-selectin和NF-κB表达减弱．结论:肠缺血再灌注诱发肝损伤,伴有明显的中性粒细胞浸润和肝组织P-selectin的表达增强,NF-κB的活化在此损伤过程中起重要作用． PDTC通过抑制NF-κB活性对肠缺血再灌注肝损伤起保护作用．     

FoxO1变化对糖尿病小鼠心肌缺血/再灌注损伤的影响

目的:观察心肌中插头转录因子O1（FoxO1）在糖尿病（DM）小鼠心肌中表达量变化及对小鼠心肌缺血/再灌注（I/R）损伤的影响。方法: 将90只健康雄性Swiss小鼠随机分为5组:假手术（Sham）组、I/R组、DM+Sham组、DM+I/R组及DM+FoxO1SiRNA+I/R组,每组18只。采用高糖高脂饮食加链脲菌素(Streptozocin,STZ)腹腔注射诱导建立DM小鼠模型。采用FoxO1SiRNA心肌点注射下调心肌FoxO1表达。心肌I/R损伤模型的建立,采用结扎心脏冠状动脉左前降支30 min后再灌注方案实施。心肌再灌注3 h后,用原位缺口末端标法(TUNEL)检测心肌细胞凋亡。用ELISA法检测心肌中 Caspase-3的活性。用Western blot法检测心肌中FoxO1的表达量。心肌再灌注24 h后,用2,3,5-三苯基氯化四氮唑（TTC）染色法检测心肌梗死（MI）的面积。结果: 与Sham组比较,DM+Sham组心肌中FoxO1的表达量明显增高（P<0.01）。与I/R组比,DM+I/R组MI的面积增大（P<0.05）,心肌细胞凋亡数量及Caspase-3活性明显增加（P<0.01）。与DM+I/R组相比,DM+FoxO1SiRNA+I/R组心肌FoxO1的表达量下调（P<0.05）,MI面积及Caspase-3的活性减小（P<0.05）,心肌细胞凋亡数量减少（P<0.01）。结论: DM小鼠心肌中FoxO1表达量的增加可加重心肌I/R损伤;而下调心肌中FoxO1的表达量后,心肌I/R损伤减轻。     

Impact of intestinal ischemia/reperfusion and lymph drainage on distant organs in rats

AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank,sham,I/R,and ischemia/reperfusion and drainage(I/R + D) groups(n = 8).All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion.The rats in the I/R + D group received intestinal lymph drainage for 180 min.In the sham group,the abdominal cavity was opened for 180 min,but the rats received no treatment.The blank group served as a normal and untreated control.A chromogenic limulus assay kit was used for quantita-tive detection of serum endotoxin.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,soluble cell adhesion molecules(sICAM-1),and high mobility group protein box 1(HMGB1) were determined with an enzyme-linked immunosorbent assay kit.Histological evaluations of the intestine,liver,kidney,and lung were performed by hematoxylin and eosin staining and immunohistochemistry.HMGB1 protein expression was assayed by western blot analysis.RESULTS:The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group(endotoxin,I/R and I/R + D vs sham:0.033 ± 0.004 EU/mL,0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL,respectively,P 0.05;HMGB1,I/R and I/R + D vs sham:5.473 ± 0.963 EU/mL,4.906 ± 0.552 EU/mL vs 0.476 ± 0.406 EU/mL,respectively,P 0.05).In addition,endotoxin and HMGB1 were significantly lower in the I/R + D group compared to the I/R group(P 0.05).The serum inflammatory factors IL-6,IL-1β,and sICAM-1 in the I/R and I/R + D groups were significantly higher than those in the sham group(IL-6,I/R and I/R + D vs sham:41.773 ± 9.753 pg/mL,19.204 ± 4.136 pg/mL vs 11.566 ± 2.973 pg/mL,respectively,P 0.05;IL-1β,I/R and I/R + D vs sham:144.646 ± 29.378 pg/mL,65.829 ± 10.888 pg/mL vs 38.178 ± 7.157 pg/mL,respectively,P 0.05;sICAM-1,I/R and I/R + D vs sham:97.360 ± 12.714 ng/mL,48.401 ± 6.547 ng/mL vs 33.073 ± 5.957 ng/mL,respectively;P 0.05).The serum TNF-α in the I/R group were significantly higher than in the sham group(45.863 ± 11.553 pg/mL vs 18.863 ± 6.679 pg/mL,respectively,P 0.05).These factors were significantly lower in the I/R + D group compared to the I/R group(P 0.05).The HMGB1 immunohistochemical staining results showed no staining or apparent injury in the blank group,and slight staining at the top of the microvillus was detected in the sham group.In the I/R group,both the top of villi and the basement membrane were stained for HMGB1 in most areas,and injury in the I/R + D group was less than that in the I/R group.HMGB1 expression in the liver,kidney,and lung of rats in the I/R + D group was significantly lower than the rats in the I/R group(P 0.05).CONCLUSION:Lymph drainage could block the "gutlymph" pathway,improve intestinal barrier function,and attenuate distant organ injury incurred by intestinal I/R.     

一氧化氮与肺缺血再灌注损伤的研究进展

一氧化氮（nitricoxide，NO）是一种活性很强的自由基，具有广泛的生物学活性。多项研究提示NO在急性肺缺血／再灌注（ischemia／reperfusion，I／R）损伤中具有重要作用。本文重点描述有关一氧化氮在肺I／R损伤中作用的研究进展。     

复发木尼孜其颗粒对大鼠心肌缺血/再灌注损伤的保护及其与核因子NF-κB信号通路的相关性

目的 探讨复方木尼孜其颗粒（Munziq）对大鼠模型心肌缺血/再灌注损伤（MIRI）的影响及其机制。方法 选择70只SD大鼠随机分为4组:正常假手术组（简称Con组）10只、正常缺血再灌注组（简称IR组）20只、复方木尼孜其颗粒组（5.06g/kg）20只、阿托伐他汀组（AT,20 mg/kg）20只,灌胃干预21天。检测各组心肌组织NIK, IKKα,pIKKα,及 p65表达及血清CTN-T、CK-MB、LDH、MDA IL-1β, IL-6, TNF-α, IL-10 及 ICAM-1含量。结果：心肌HE染色中复方木尼孜其组和阿托伐他汀组心肌细胞出现轻度颗粒变性和空泡变性。红细胞和淋巴细胞浸润,血管扩张和充血几乎没有观察到。同样这两组损伤心肌细胞的病理学特征均明显减轻。心肌细胞肿胀减少。cTn-T, CK-MB, LDH, 及 MDA水平变化：MIRI组的CTN-T、CK-MB、LDH、MDA水平显著高于假手术组（P＜0.05）。与MIRI组比较,复方木尼孜其颗粒和阿托伐他汀组的CTN-T、CK-MB、LDH、MDA含量显著降低（P＜0.05）。NIK, IKKα, pIKKα,及p65水平的变化：与假手术组相比,MIRI组的NIK、IKKα、PIKKα、P65水平显著高于对照组（P＜0.05）。而复方木尼孜其组和阿托伐他汀组的上述蛋白含量明显低于MIRI组（P＜0.05）。IL-1β, IL-6, TNF-α, IL-10 及 ICAM-1.水平变化： MIRI组IL-1β、IL-6、TNF-α、IL-10水平均高于假手术组（P＜0.05）。假手术组与MIRI组比较有显著性差异（P＜0.05）。复方木尼孜其与MIRI组、阿托伐他汀组和MIRI组比较差异有统计学意义（P＜0.05）。结论 复方木尼孜其颗粒在缺血再灌注损伤中具有心脏保护作用。这种作用可能通过抑制NF-κB信号通路来发挥作用。复方木尼孜其颗粒可能作为保护心脏围手术期心肌缺血再灌注损伤的干预药物。     

内皮素-1与肺缺血/再灌注损伤的实验研究

目的 :探讨内皮素 -1（ET-1）在肺缺血 /再灌注 （I/ R）损伤中的作用。方法 :健康新西兰大白兔 3 0只随机分成 3组 （每组 10只 ） :假手术组 （ 组 ）、I/ R+生理盐水 （ 组 ）和 I/ R+ ET-1抗体组 （ 组 ）。观察肺再灌注 0 ,60 ,12 0 ,2 40min各时间点肺动脉压 （PA）、动脉氧分压 （Pa O2 ）和血浆 ET-1的变化。实验结束时 ,检测支气管肺泡灌洗液（BAL F）中 ET-1和肺组织丙二醛 （MDA）的含量和肺组织光镜的变化。结果 : 组血浆和 BAL F的 ET-1水平、肺组织 MDA含量和 PA升高 ,Pa O2 降低。 组 PA和 Pa O2 没有明显变化 ,血浆和 BAL F的 ET-1水平、肺组织 MDA含量的升高得到抑制。结论 :ET-1参与肺缺血 /再灌注损伤 ,能改善 PA和 Pa O2 。     

Panax notoginseng saponins attenuate acute lung injury induced by intestinal ischaemia/reperfusion in rats

Background and objective:   Acute lung injury remains a challenge for both clinicians and scientists. The effects of Panax notoginseng saponins (PNS) on acute lung injury induced by intestinal ischaemia/reperfusion (II/R) were studied in rats.
Methods:   Forty-eight Wistar rats were randomly assigned to four groups: (1) a sham-operated group that received laparotomy without II/R ( n = 12); (2) a sham + PNS group, which was identical to group 1 except for PNS treatment ( n = 12); (3) an II/R group that had 1 h of intestinal ischaemia followed by 3 h of reperfusion ( n = 12); and (4) an II/R + PNS group that received 100 mg/kg of PNS, i.v., 15 min before reperfusion ( n = 12). The effects of PNS administration on lung tissue histology, activities of oxidant and antioxidant enzymes, levels of malondialdehyde, nitric oxide and inducible nitric oxide synthase activity were examined. Levels of surfactant protein B, cell numbers in BAL fluid and plasma levels of pro-inflammatory cytokines were also examined.
Results:   Compared with the II/R group, pulmonary parenchymal damage, activities of oxidant enzymes, levels of malondialdehyde and nitric oxide, inducible nitric oxide synthase activity in lung tissue, and plasma levels of pro-inflammatory cytokines were significantly reduced by PNS treatment. In addition, the decreases in antioxidant enzyme activities were prevented in the II/R + PNS group. Total leukocyte and neutrophil counts were significantly decreased by PNS treatment. The decline in surfactant protein B levels in BAL fluid was reduced in the II/R + PNS group compared with the II/R group.
Conclusions:   Administration of PNS before reperfusion injury alleviates acute lung injury induced by II/R, and this is attributable to the antioxidant and anti-inflammatory effects of PNS.     

Expression and significance of nuclear factor κB p65 in colon tissues of rats with TNBS-induced colitis

AIM: To investigate the role of NF-κB in the pathogenesis of TNBS-induced colitis in rats. METHODS: Thirty-two healthy adult Sprague-Dawley (SD) rats were randomly divided into four groups of eight each: normal, NS, model Ⅰ, model Ⅱ groups in our study. Rat colitis model was established through 2-,4-,6-trinitrobenzene sulfonic acid (TNBS) enema. At the end of four weeks, the macroscopical and histological changes of the colon were examined and mucosa myeloperoxidase (MPO)activities assayed. NF-~B p65 expression was determined by Western blot assessment in cytoplasmic and nuclear extracts of colon tissue, and the expressions of TNF-α (and ICAM-1 protein in colon tissue were examined by immunohistochemistry. The relativities between expression of NF-κB p65 and other parameters were analyzed. RESULTS: TNBS enema resulted in pronounced pathological changes of colonic mucosa in model Ⅱ group (macroscopic and histological injury indices 6.25&#177;1.39 and 6.24&#177;1.04, respectively), which were in accordance with the significantly elevated MPO activity (1.69+0.11). And the nuclear level of NF-κB and expression of TNF-α, ICAM-1 in rats of model Ⅱ group were higher than that of normal control(9.7&#177;1.96 vs 1.7&#177;0.15, 84.09&#177;14.52 vs 16.03&#177;6.21,77.69&#177;8.09 vs 13.41&#177;4.91 P&lt;0.01), Linear correlation analysis revealed that there were strong correlations between the nuclear level of NF-κB and the tissue positive expression of TNF-α and ICAM-1, MPO activities, macroscopical and histological indices in TNBS-induced colitis, respectively (r = 0.8235, 0.8780, 0.8572, 0.9152,0.8247; P&lt;0.05). CONCLUSION: NF-κB plays a pivotal role in the pathogenesis of ulcerative colitis, which might account for the up-regulation the expression of TNF-α and ICAM-1.     

乙肝患者外周血ICAM-1的检测意义

探讨乙肝患者外周血中性粒细胞细胞间粘附分子-1(ICAM-1)的变化及其意义。应用流式细胞仪检 测28例慢性轻度肝炎,24例慢性中、重度肝炎,28例肝硬化患者外周血ICAM-1的表达,同时Beckman公司生化仪 CX4测定了ALT。肝炎和肝硬化患者外周血中性粒细胞的ICAM-1表达和血清ALT水平都显著高于正常对照组。 实验组中两两比较发现慢性轻度肝炎与慢性中、重度肝炎、肝硬化ICAM-1、ALT之间有明显差异,肝硬化患者与慢 性中、重度肝炎之间无明显差异。同时发现ICAM-1的过度表达与血清ALT的活性呈正相关。ICAM-1水平可作 为反映肝炎后肝病患者肝损害程度的指标之一。