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Intra-pulmonary Artery Infusion of Antitumor Necrosis Factor-α Antibody Attenuates Lung Injury after Cardiopu-lmonary Bypass

Objective To investigate the protective effects of antitumor necrosis factor-α antibody （TNF-αAb） on lung injury after cardiopulmonary bypass （CPB） and their mechanisms. Methods Forty healthy New Zealand white rabbits，weighting 2.0-2.5 kg，male or female，were randomly divided into 4 groups with 10 rabbits in each group. In groupⅠ，the rabbits received CPB and pulmonary arterial perfusion. In group Ⅱ，the rabbits received CPB and pulmonary arterial perfusion with TNF-αAb. In group Ⅲ，the rabbits received CPB only. In group Ⅳ，the rabbits only received sham surgery. Neutrophils count，TNF-α and malondialdehyde （MDA） concentrations of the blood samples from the left and right atrium as well as oxygenation index were examined before and after CPB in the 4 groups. Pathological and ultrastructural changes of the lung tissues were observed under light and electron microscopes. Lung water content，TNF-α mRNA and apoptoticindex of the lung tissues were measured at different time points. Results Compared with group Ⅳ，after CPB，the rabbitsin group Ⅰ to group Ⅲ showed significantly higher blood levels of neutrophils count，TNF-α and MDA（P＜0.05），higherTNF-α mRNA expression，apoptosis index and water content of the lung tissues （P＜0.05），and significantly lower oxyg-enation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with group Ⅱ，after CPB，the rabbits in groups Ⅰ and Ⅲ had significantly higher blood concentrations of TNF-α （5 minutes after aortic declamping，220.43±16.44 pg/ml vs.185.27±11.78 pg/ml，P＜0.05；249.99±14.09 pg/ml vs.185.27±11.78 pg/ml，P＜0.05），significantly higher apoptosis index （at the time of CPB termination，60.7‰±13.09‰ vs. 37.9‰±7.78‰，P＜0.05；59.6‰±7.74‰ vs. 37.9‰±7.78‰，P＜0.05），significantly higher blood levels of neutrophils count and MDA （P＜0.05），significantly higher TNF-α mRNA expression and water content of the lung tissues （P＜0.05），and significantly loweroxygenation index （P＜0.05） as well as considerable pathomorphological changes in the lung tissues. Compared with groupⅠ，rabbits in group Ⅲ had significantly higher above parameters （P＜0.05） but lower oxygenation index （P＜0.05） only at 30 minutes after the start of CPB. Conclusion Pulmonary artery perfusion with TNF-αAb can significantly attenuate inflammatory lung injury and apoptosis of the lung tissues during CPB.

THE RELATIONSHIP OF MACROPHAGES,TUMOR NECROSIS FACTOR AND INTERLEUKIN 1 WITH THE FORMATION OF HUMAN CHOLESTEROL GALLSTONES

63 normal human gallbladders (non-stone group) and 47 inflammed cholesterol stone gallbladders(stone group) were assayed for the amount of macrophages(ΜΦ),the levels of tumor necro-sis factor (TNF) and interleukin 1(1L-1).It was found that in stone group,the amount of ΜΦ was significantly higher than in non-stone group(ΜΦ4101.90±295.72 vs 572.13±30.07AU,Plt;0.01).The levels of TNF and 1L-1 released mainly from the MΦ in stone group were also significantly increased in comparison with those in non-stone group(TNF 18.12±2.03 vs 4.45±0.39ng/mg,Plt;0.001;1L-1 102.42±7.84 vs 66.75±9.50u/mg protein,Plt;0.05).These results suggest that the activited ΜΦ and increases of TNF,1L-1 may be closely related to the inflammatory reaction in gallbladders and the formation of cholesterol gallstones.

Effects of Ecdysterone on the Expression of Tumor Necrosis Factorα and Nuclear Factor κ B in Nonalcoholic Fatty Liver Disease of Rats

摘要:目的: 研究蛻皮甾酮對非酒精性脂肪性肝病大鼠模型腫瘤壞死因子α(TNFα)與核因子κB(NFκB)表達的影響，并探索其可能的作用機制。 方法 :健康成年SD大鼠36只,隨機分為正常對照組12只與實驗組24只;正常對照組喂以普通基礎飼料,實驗組應用高脂飼料喂養。實驗12周末時將造模成功的實驗組大鼠隨機分為模型組與蛻皮甾酮治療組2個亞組,每組12只;正常對照組喂以普通基礎飼料至16周,模型組繼續應用改良高脂飼料喂養至16周,蛻皮甾酮治療組大鼠在高脂飲食同時加用蛻皮甾酮灌胃。實驗16周末時處死3組所有大鼠;檢測肝臟指數,血清與肝組織生化指標及肝組織病理改變;ELISA法檢測肝臟TNFα水平;免疫組化檢測各組大鼠肝組織中核因子κB蛋白表達情況。 結果 :蛻皮甾酮治療組血清膽固醇(TC)、丙氨酸氨基轉移酶(ALT)和天門冬氨酸氨基轉移酶(AST)明顯低于模型組(212±058比263±024,Plt;005;5336±1848比8460±3627,P＜005;14020±3595比24359±3638,P＜001);蛻皮甾酮治療組與模型組相比肝組織丙二醛(MDA)水平降低明顯(18454±1645比23928±2376,P＜001),超氧化物歧化酶(SOD)活力增加顯著(942±052比518±043,P＜001),肝臟指數顯著降低(435±037比504±046,P＜001)，肝組織脂肪變性程度和炎癥活動度明顯減輕(546±037比630±049,P＜001)。蛻皮甾酮治療組與模型組相比TNFα與核因子κB水平明顯減輕(4304±748比6156±727,2465±539比4504±746,P值均＜001)。 結論 :蛻皮甾酮具有改善高脂飲食誘發的非酒精性脂肪性肝病大鼠肝臟酶學功能,通過增加肝組織SOD的含量和減少MDA的含量來減輕肝組織氧化應激水平,減輕肝組織TNFα和核因子κB來減輕肝臟炎癥,發揮防治非酒精性脂肪性肝病的作用。Abstract: Objective: To investigate the effect and possible mechanism of ecdysterone on the expression of tumor necrosis factoralpha (TNFα) and nuclear factor κ B (NFκB) in rats with nonalcoholic fatty liver disease of rats. Methods : A total of 36 male Sprague Dawley rats were randomly divided into two groups, who were fed with highfat diet (experimental group, n=24) and normal basic food (normal control, n=12) respectively. At the end of the 12th week, the experimental group was randomly divided into two subgroups: model group and ecdysterone group, each group contained 12 rats. From the 13th week, the rats in the normal control group and model group were lavaged with normal sodium, and the rats in the ecdysterone group were lavaged with ecdysterone at 10 mg·kg-1·d-1. At the end of the 16th week, all rats were weighed, narcotized, sacrificed, and the liver index, biochemical indicators in serum and liver tissues and the hepatic pathological changes were observed. The expression of TNFα was detected by ELISA and the expression of NFκB was measured by immunohistochemical staining. Results : At the end 16th week in ecdysterone group, the serum levels of cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reduced markedly (212±058 vs 263±024 and 5336±1848 vs 8460±3627, both P＜005; 14020±3595 vs 24359±3638, P＜001); the tissue content of malondialdehyde (MDA) was decreased evidently (18454±1645 vs 23928±2376, P＜001), while the activity of superoxide dismutase (SOD) was enhanced notably (942±052 vs 518±043, P＜001); the liver index was decreased significantly in comparison with that inmodel group (435±037 vs 504±046, P＜001); the degree of fatty degeneration and inflammation were relieved dramatically (546±037 vs 630±049, P＜001). The expression of TNFα and the levels of NFκB were significantly lower (4304±748 vs 6156±727 and 2465±539 vs 4504±746, both P＜001) in ecdysterone group compared with model group. Conclusion : The effects of ecdysterone in preventing NAFLD in rats could be related to the increase of SOD content in hepatic tissue and the decrease of MDA content, tumor necrosis factorα and NFκB.

Experimental Study of Relationship of Zonula Occludens-1 and Microvascular Injury in Rats with Severe Acute Pancreatitis

Objective To investigate the changes of expression of zonula occludens-1(ZO-1) in rats with severe acute pancreatitis (SAP), and to study the relationship between the ZO-1 protein and microvascular injury in rats with SAP. Methods Forty-eight Wistar rats were randomly divided into sham-operation (SO) group and SAP group, each group enrolled 24 rats. Pancreas of rats in SO group were flipped only after laparotomies, but rats of SAP group were injected with 5% sodium taurocholate by retrograding cholangiopancreatography micro pump to produce the SAP model. At 6, 12, and 24 hours after operation, 8 rats were sacrificed to get abdominal aortic blood for testing the levels of peripheral blood amylase, trypsin, interleukin-8(IL-8), tumor necrosis factor-α(TNF-α), and ZO-1 protein. At the same time, pancreatic tissues were got to perform HE staining and immunohistochemical staining for observation of the pathological changes and the expression of ZO-1 protein respectively. Results Compared with SO group at the same time, the levels of peripheral blood amylase, trypsin, IL-8, TNF-α, and ZO-1 protein were all higher in SAP group (P < 0.05). The level of amylase in SAP-24 hours group was higher than those of 6 hours group and 12 hours group(P < 0.05), the levels of trypsin, IL-8, and ZO-1 protein in SAP group increased over time (P < 0.05), but levels of TNF-αin 3 time points of SAP group did not differ with each other significantly(P > 0.05). Results of regression showed that in the SAP group, the level of ZO-1 protein in serum was significantly positive correlated with pathological score of pancreatic tissue(b=0.96, P < 0.05), levels of serum amylase(b=0.87, P < 0.05), trypsin(b=0.72, P < 0.05), and serum IL-8 (b=0.69, P < 0.05), but was not significantly correlated with level of TNF-α(P > 0.05). HE staining results showed that damage of pancreatic tissues became worse over time in SAP group, and the pathological score of SAP-6 hours group was lower than those of 12 hours group and 24 hours group (P < 0.05). Immunohistochemical staining results showed that, in SAP group, with the extension of time, the number of ZO-1 protein granules in pancreatic acinar cells and capillary wall reduced, and expressed in capillaries discontinuously. Conclusion During the course of SAP, the concentration of serum ZO-1 protein increase, but its expression in the pancreatic tissue degrade, which is closely associated with microvascular injury and progression of pancreatic tissues.

EFFECT OF TUMOR NECROSIS FACTOR ON ACUTE NECROTIZING PANCREATITIS OF MONKEYS AND THERAPEUTIC EFFECT OF STILAMIN

In the early stage of acute necrotizing pancreatitis (ANP) of experimental monkeys, the concentration of tumor necrosis factor (TNF) in blood was significantly increased. Stilamin could significantly reduce the level of TNF, decrease the mortality, and prolong the survival time of monkeys. The authors draw the conclusion that TNF is an important inflammatory media in the early stage of ANP. Stilamin can significantly inhibit the inflammatory process and has good effect in the treatment of ANP in experimental monkeys.

Effects of Early Hemofiltration on TNF-α and IL-1β in Pigs with Severe Acute Pancreatitis

【Abstract】Objective To study the influence of early hemofiltration on plasma concentrations of proinflammatory cytokines TNF-α and IL-1β and their transcription levels in severe acute pancreatitis (SAP) pigs. Methods The model of SAP was induced by retrograde injection of artificial bile into pancreatic duct in pigs. Animals were divided randomly into two groups: SAP hemofiltration treatment group (HF group, n=8) and SAP no hemofiltration treatment group (NHF group, n=8). TNF-α and IL-1β plasma concentrations were measured by ELISA. Their transcription levels in the tissues of pancreas, liver and lung were assayed by semi-quantitative reverse transcription polymerase chain reaction. Results After hemofiltration treatment, the plasma concentrations of TNF-α and IL-1β increased gradually but were lower than those of NHF group at the same time spot 〔at 6 h after hemofiltration treatment, (618±276) pg/ml vs (1 375±334) pg/ml and (445±141) pg/ml vs (965±265) pg/ml, P＜0.01〕. At 6 h after hemofiltration treatment, the transcription levels of TNF-α and IL-1β in tissues of pancreas, liver and lung were lower than in NHF group (57.8±8.9 vs 85.7±17.4, 48.0±8.1 vs 78.1±10.2, 46.2±9.6 vs 82.4±10.5; 55.9±9.0 vs 82.2±15.7, 40.6±9.2 vs 60.0±10.6, 35.7±9.8 vs 58.1±9.3, P＜0.01). Conclusion Early hemofiltration can reduce TNF-α and IL-1β plasma concentrations and transcription levels in SAP pigs.

急性胰腺炎時腫瘤壞死因子的變化

EXPRESSION OF TNFα mRNA IN LIVER AFTER ENDOTOXEMIA IN MICE AND ITS SIGNIFICANCE

Objective To investigate the effects of expression of TNFα mRNA on glucose uptake in both the liver and skeletal muscle after endotoxemia. Methods In the mice with intraperitoneal injection of lipopolysaccharide (LPS), the changes of TNFα level of plasma and uptake of 2-deoxyglucose (2-DG) in the isolated soleus muscle and hepatic tissues were determined, then the reinstatement of glucose uptake by injecting TNF-McAb for 3 days was also observed. In addition, changes of TNFα mRNA expression of liver were evaluated. Results The expression of TNFα mRNA in the liver showed markedly increased in the first 3 hours post endotoxemia and remaind high for 3 days, and the plasma TNFα level paralleled with TNFα mRNA expression of liver also was elevated. The basal uptake of 2-DG both in muscle and liver were markedly increased, but the stimulated 2-DG uptake with insulin was greatly reduced as compared with the control. In addition, these abnormalities of 2-DG uptake can be partially corrected by neutralization of the circulatory TNFα by administration of TNF-McAb. Conclusion The disorders of glucose uptake of the liver and the muscle due to the overexpression of TNFα mRNA and elevated circulatory TNFα level may be the mechanism of insulin resistance after endotoxemia.

Analysis of Time and Causes of Death of 211 Cerebral Hemorrhage Patients

目的:分析腦出血死亡時間及死因,找出腦出血不同死亡時間的主要死因,為制定腦出血不同時間的相應救治措施提供依據。方法:回顧性總結分析２１１ 例腦出血死亡病例的死亡時間、主要死因,找出不同死亡時間對應的主要死因。 結果: (１)死亡時間:≤３ 天 ９１ 例、４~７天 ５２ 例、８~１４ 天 ４２ 例、１５~２１ 天１８ 例、２２~２８ 天 ７ 例、≥ ２９ 天 １ 例。(２)死亡原因:１６９ 例死于腦疝及中樞性呼吸、循環衰竭;20例死于肺部感染;１０ 例死于消化道出血;4 例死于多器官功能衰竭;４ 例死于心臟病變(如心臟猝死、心肌梗塞、心功能衰竭);其它４例(痰窒息、腎功能衰竭、肝功能衰竭)。(３)不同死亡時間主要死亡原因:≤３ 天 ９０ 例死于腦疝及中樞性呼吸、循環衰竭,僅 １ 例死于消化道出血;４～７ 天４７ 例死于腦疝及中樞性呼吸、循環衰竭,３ 例死于肺部感染,死于心臟病變及其它各１例;８~１４ 天 ２９ 例死于腦疝及中樞性呼吸、循環衰竭,８ 例死于肺部感染,２ 例死于消化道出血,死于心臟病變、多器官功能衰竭、其它各 １ 例;１５~２１ 天 ７ 例死于肺部感染,５ 例死于消化道出血,３ 例死于腦疝及中樞性呼吸、循環衰竭,死于心臟病變、多器官功能衰竭、其它各１例;２２～２８天死于消化道出血、肺部感染各２ 例,死于心臟病變、多器官功能衰竭、其它各１ 例,已無死于腦疝及中樞性呼吸、循環衰竭者;２９ 天后死于多器官功能衰竭１ 例。結論: 腦出血死亡時間不同,其主要死亡原因不同。臨床應該針對不同死亡時間的主要死因制定相應救治方案,以降低死亡率。

The Expression and Implication of Serum Adiponectin in Patients with Asthma

Objective To measure the serum level of adiponectin and explore its clinical implication in patients with asthma in acute exacerbation and remission phase. Methods 97 patients with asthma were recruited, including 50 patients with asthma in acute exacerbation and 47 patients in remission phase fromOctober 2010 to September 2011. 27 healthy nonsmoking volunteers of normal weight ( BMI range of 18.5-24. 9 kg/m2 ) were included as control. The concentrations of adiponectin and tumor necrosis factor alpha ( TNF-α) in serum were measured by enzyme-linked immunosorbent assay ( ELISA) . The lung function was tested in all subjects. The correlations between adiponectin, TNF-αand lung function were investigated. The data was analyzed using SPSS 19. 0 software. Variables were compared with one-way ANOVA. The correlations between variables were analyzed using Peason’s correlation coefficient or Spearman correlation coefficient.Results Serum adiponectin level was significantly lower in the patients with asthma in acute exacerbation [ ( 246 ±1. 21) ng/mL] than that in the healthy subjects [ ( 9. 64 ±4. 88)ng/mL] and the patients in remission phase [ ( 3. 79 ±0. 96) ng/mL] ( P lt; 0. 01) , while serum adiponectin level was also significantly lower in the patients in asthma remission phase than that in the healthy subjects ( P lt; 0. 01) . The serum adiponectin level in the patients with asthma in acute exacerbation or in asthma remission phase was negatively correlated with the serum TNF-α level ( P lt; 0. 01) , and was positively correlated with FEV1 /predicted value ( P lt; 0. 01) . Conclusions The serum adiponectin is reduced in asthma patients and may play a protective role in asthma.