SOCS3在实验性急性胰腺炎急性肺损伤大鼠肺组织中的表达和作用

背景：细胞因子信号转导抑制分子3（SOCS3）在多种疾病的各种器官损伤中起重要的调节作用,可通过对JAK/STAT信号通路的负反馈作用调节炎症因子的释放,从而起一定的抑炎作用。目前关于SOCS3在重症急性胰腺炎（SAP）急性肺损伤中的表达和作用尚未见报道。目的：探讨SOCS3在实验性急性胰腺炎（AP）合并急性肺损伤大鼠肺组织中的表达变化及其可能的作用。方法：32只Sprague-Dawley大鼠随机分为对照组和AP 6 h、12 h、18 h组。以4%牛磺胆酸钠胰胆管逆行注射诱导AP模型。动态测定各组血清淀粉酶（AMY）水平、肺湿/干重比;光学显微镜下观察肺组织学表现;ELISA法检测血清白细胞介素（IL）-6、IL-18含量;免疫组化法和蛋白质印迹法检测肺组织中SOCS3的定位和表达。结果：与对照组相比,各AP模型组血清AMY水平、肺湿/干重比均明显升高（P〈0.05）;肺组织损伤随病情进展而逐渐加重;血清IL-6、IL-18水平显著上调（P〈0.05）;肺组织SOCS3表达逐渐增强（P〈0.05）,于18 h时达高峰。结论：SAP急性肺损伤导致的炎症反应可诱导SOCS3在肺组织中表达,并随着肺组织损伤和炎症反应严重程度的增加而逐渐增高,提示可能与其负反馈调节JAK/STAT信号通路介导的炎症反应的作用存在一定的联系。     

清胰汤对急性胰腺炎肺损伤治疗作用的实验研究

[目的]探讨清胰汤在重症急性胰腺炎（SAP）急性肺损伤（ALI）时对肺表面活性蛋白A（SP-A）表达及病情转归的影响。[方法]将SD大鼠随机分为3组，各10只。假手术（对照）组仅行剖腹术，模型组采用胆胰管内逆行注入1．5％去氧胆酸钠建立大鼠SAP时ALI模型，清胰汤治疗（治疗）组在建立SAP模型后30min、12h清胰汤（10ml／kg）灌胃。各组术后24h测动脉血pH、动脉氧分压（PaO2）、动脉二氧化碳分压（PaCO2）、血淀粉酶（AMY）、肺湿／干重（W／D）比值。应用RT-PCR检测肺sP-A mRNA的表达强度，并观察胰、肺病理变化。[结果]模型组AMY、W／D及PaCO2显著高于对照组和治疗组（均P〈0．01）。而模型组pH、PaO2显著低于其他2组（P〈0．05，〈0．01）。治疗组肺sP-A mRNA表达显著高于模型组（P〈0．01），其表达与肺损伤的程度呈负相关。治疗组胰、肺病理改变较模型组减轻。[结论]清胰汤能保护肺泡Ⅱ型上皮细胞功能，恢复SP-A mRNA正常表达，维持肺泡功能，从而对肺组织起保护作用。     

实验性重症急性胰腺炎肺内IL—1β及IL—18mRNA的表达

目的：观察实验性重症急性胰腺炎（severe acute pancreatitis,SAP）肺内IL－1β及IL－18mRNA的表达，并探讨其与肺损伤的关系，方法：SD大鼠32只，随机分4组：正常对照组、SAP6h组、SAP12h组、SAP18h组。采用5％牛磺胆酸钠（0.1ml/100g）胆胰管内逆行注射诱导大鼠SAP模型。血清淀粉酶采用HITACHI－7150型自动生化分析仪测定；半定量RT－PCR检测肺组织内IL－1β及IL18mRNA的表达，结果：造模后各时间点血清淀粉酶水平显升高，12h达到高峰，与正常对照组相比，均具有显性差异（P＜0．01）。正常肺组织内可见IL－1β及IL－18mRNA表达；SAP各组肺组织内IL－1β及IL－18mRNA的表达明显增强，与正常对照组比较均有显性差异（P＜0．01），结论：除TNF-α外，肺内生成过多的IL－1β及IL－8在SAP并发急性肺损伤（acute lung injury,ALI）及急性呼吸窘迫综合征（acute respiratory distress sysdrome,ARDS)进程中可能发挥重要的作用。     

趋化因子Fractalkine在急性肝功能衰竭大鼠模型中的变化及意义

目的 探讨不规则趋化因子Fraetalkine(FKN,CX3CLl)在急性肝功能衰竭大鼠模型中的变化及其在肝脏炎性损伤中的作用.方法 SD大鼠分为健康对照组6只,模型组36只.D氨基半乳糖(D-Gal)诱导大鼠急性肝功能衰竭模型,造模后分别在12、24、48、72、120和168 h等6个时间点取大鼠血及肝脏标本,RT-PCR法检测肝组织中FKN mRNA、核因子(NF)-kB mRNA的变化.计量资料组间比较用t检验,相关性检验用Pearson直线相关分析.结果 造模后12 h,大鼠血ALT、AST值明显升高,分别为(208.3±43.5)U/L和(375.25:117.3)U/L,显著高于正常组的(31.8±2.9)U/L和(90.8±3.1)U/L,差异有统计学意义(t值分别为-9.912和-5.935,P＜0.01),72 h达高峰.造模后12 h,FKN mRNA为0.086±0.009,高于正常组的0.044±0.009,差异有统计学意义(t=-7.999,P＜0.01),72 h达高峰,为0.333±0.033,120 h则明显下降.NF-kB在正常大鼠肝组织中有少量表达,模型组随着时间推移,NF-kB水平逐渐升高,72 h达高峰,为0.583±0.101(t=-12.607,P＜0.01).FKN与NF-kB呈正相关(r=0.760,P＜0.01).结论 FKN在急性肝功能衰竭大鼠中的表达是肝损伤的重要因素,有可能为急性肝功能衰竭的治疗提供一个新的切入点.     

Sodium Butyrate Reduces Organ Injuries in Mice with Severe Acute Pancreatitis Through Inhibiting HMGB1 Expression

Objective

The present study was designed to evaluate the effect of sodium butyrate on pancreas damage and to investigate the role of high-mobility group box-1 (HMGB1) and nuclear factor-κB (NF-κB) in the development of severe acute pancreatitis (SAP) in a mouse model.

Methods

The SAP model was established by intraperitoneal injection of two doses of 20 % L-2 arginine (200 mg/g). Female Sprague–Dawley mice were randomly allocated into three groups (n = 48/group): the control, untreated SAP, and sodium butyrate-treated SAP groups. The animals were euthanized at 0, 12, 24, and 48 h after the establishment of the SAP. Histopathology of the pancreas was performed, and the NF-κB levels were determined by immunohistochemistry. The serum levels of tumor necrosis factor (TNFα), interleukin-6 (IL-6), and HMGB1 were measured by ELISA. The HMGB1 mRNA levels were determined by qRT-PCR.

Results

The sodium butyrate-treated SAP animals showed significantly improved pancreas histopathology and lower serum amylase levels than the untreated SAP animals. In the SAP group, the mRNA levels of HMGB1 were remarkably increased at the 12 h, peaked at 24 h, and remained at a high level up to 48 h after L-2 arginine injection. The levels of TNFα and IL-6 were decreased at 48 h. Treatment with sodium butyrate reduced the pathological lesions, the serum levels of HMGB1, TNFα, and IL-6, the HMGB1 mRNA levels, and NF-κB activity.

Conclusion

Sodium butyrate inhibits the NF-κB activation and reduces pancreas injury in SAP through the modulation of HMGB1 and other inflammatory cytokine responses.

     

SOCS3在重症急性胰腺炎大鼠胰腺中的表达和作用

目的:探讨细胞因子信号转导抑制子3(SOCS3)在实验生重症急性胰腺炎(SAP)中的表达和作用.方法:32只♂ Sprague-Dawley大鼠随机分为对照组(NC组)和3组SAP 6 h、12 h、18h组,每组8只.以4％牛磺胆酸钠胰胆管逆行注射诱导SAP模型,动态测定各组血清淀粉酶(AMY)水平;光镜下观察胰腺大...     

Interleukin-22 ameliorates acute severe pancreatitisassociated lung injury in mice

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.     

重症急性胰腺炎肠内营养治疗的大鼠模型

目的旨在建立适用于研究重症急性胰腺炎(SAP)营养治疗的大鼠模型,为SAP肠内营养(EN)研究提供实验和理论依据。方法80只SD大鼠,体重(200±10)g,随机分为对照组(共20只,分6、12、24和48h4个时间点观察组,每个时间点组为5只)和ANP组(共60只,其中20只分6、12、24和48h4个时间点观察组,每个时间点组为5只;其余40只,用于观察死亡率)。采用胰腺被膜下均匀注射3.8%牛磺胆酸钠造模,比较对照组和ANP组4个时间点血清淀粉酶和胰腺病理变化,以及观察胰外脏器的损伤程度,统计ANP组死亡率的情况。结果ANP组各时间点血清淀粉酶高于对照组,差异有显著统计学意义(P<0.01)。血清淀粉酶在造模6h后就明显升高,12h后高达(8287±179)U/L,24h仍维持在很高的水平,48h下降为(3217±249)U/L。模型诱发后随着时间进展,胰腺病理损害呈渐进性进展,胰腺组织出现出血、坏死,胰外脏器也有不同程度的损伤。ANP组动物第1、2、3、4、5、6和7天的累计死亡率分别为0(0/40)、7.5%(3/40)、20.0%(8/40)、35.0%(14/40)、40.0(16/40)、47.5%(19/40)和52.5%(21/40)。结论采用胰被膜下均匀注射3.8%牛磺胆酸钠可成功建立ANP动物模型,重复性好,病情呈渐进性发展,与人类SAP的自然病程类似,适用于进行SAP肠内营养治疗,以及需较长时间观察的研究。     

重症急性胰腺炎肺组织Ⅱ型分泌型磷脂酶A2的表达及功能改变

[目的]探讨重症急性胰腺炎(SAP)时肺组织Ⅱ型分泌型磷脂酶A2(sPLA2 -Ⅱ)的表达及功能改变.[方法]将SD大鼠随机分为假手术组(SO组,n=10)、模型组(SAP组,n=10).SO组仅行剖腹术,翻动胰腺;SAP组用去氧胆酸钠胰管逆行注射建立SAP合并肺损伤模型.2组动物在术后24 h测pH、PaQ、PaCO2、血淀粉酶、sPLA2 -Ⅱ,肺湿/干比值.应用RT-PCR、western-blot观察肺组织sPLA2-Ⅱ表达,并观察胰、肺组织病理变化.[结果]SAP组血淀粉酶、sPLA2、肺湿/干比值显著高于SO组(P＜0.05).SAP组PaO2、pH显著低于SO组(P＜0.05),PaCO2、sPLA -Ⅱ显著高于SO组(P＜0.05).[结论]AAP时肺组织sPLA2 -Ⅱ表达增高,可能是急性肺损伤的发病机制之一.     

Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis

INTRODUCTIONIn severe acute pancreatitis (SAP), multiple organ dysfunction syndrome (MODS) in the early phase[1,2] and complications of infection (infected pancreatic necrosis and sepsis) in the late phase are contributors to high mortality in SAP[3,4]. M…     

The mRNA expression patterns of tumor necrosis factor-α and TNFR-I in some vital organs after thermal injury

AIM: To investigate changes of tumor necrosis factor-α (TNF-α and TNFR-I expression in vital organs and their significance in the pathogenesis of multiple organ damage associated with endogenous endotoxin following major burns.METHODS: Wistar rats subjected to a 35% full-thickness scald injury were sacrificed at 12h, 24h, 48h, and 72 hpostburn, respectively. Meanwhile, eight rats were taken as normal controls. Tissue samples from liver, spleen, kidney,lung and intestine were collected to assay tissue endotoxin levels and measure TNF-α and TNFR-I expression. In addition, blood samples were obtained for the determination of organ function parameters.RESULTS: Endotoxin levels in liver, spleen and lung increased markedly after thermal injury, with the highest level in liver. The gene expression of TNF-α in liver, lung and kidney was up-regulated after thermal injury, while the TNFR-I mRNA expression in liver, lung, kidney and intestine was shown decreased throughout the observation period. Thus, the mRNA expression ratio of TNF-α to TNFR-I was significantly increased postburn, particularly in pulmonary tissue (67-fold). In addition, the significant correlations between the expression of TNFR-I or the expression ratio of TNF-α/TNFR mRNA in liver tissue and serum aspartate aminotransferase levels were noted (P&lt;0.05-0.01). Similar results were also obtained between pulmonary TNF-α mRNA expression and myeloperoxidase activities (P&lt;0.01), whereas there was a highly negative correlation between levels of renal TNFR-I mRNA expression and serum creatinine.CONCLUSION: Burn injury could result in the translocation of gut-derived endotoxin that was mainly distributed in the liver, spleen and lung. The translocated endotoxin then made the expression of TNF-α and TNFR-I mRNA up-regulated and down-regulated respectively in various organs, which might be involved in the pathogenesis of multiple organ damage following burns.     

Application of Tissue Microarrays to Study the Influence of Dexamethasone on NF-κB Expression of Pancreas in Rat with Severe Acute Pancreatitis

To discuss the influence of dexamethasone on NF-κB expression of pancreas in rat with severe acute pancreatitis (SAP). Ninety rat SAP models were divided into the model group and dexamethasone treatment group with 45 rats in each group; another healthy 45 rats were selected to be the sham operation group. The groups were divided into the 3, 6 and 12 h group with 15 rats in each group. The survivals, pancreas pathological changes were observed 3, 6 and 12 h after operation. The changes in expression levels of NF-κB protein of pancreas tissue microarray were observed. The treatment group was significantly lower than the model group at 3 and 6 h (P < 0.05) and than the model group at 12 h in pancreas pathological scores (P < 0.01). The expression level of NF-κB protein of pancreas head of the treatment group was significantly less than that of the model group at 3 h (P < 0.01). The alleviation of pancreatic tissue injury by dexamethasone during SAP might be closely related to its role in inhibiting NF-κB expression and regulating cytokines. The advantages of tissue microarrays in pancreatitis pathological examination include time and energy savings, high efficiency and representative results.     

解耦联蛋白2在急性肝功能衰竭大鼠肝脏中的动态表达和意义

目的 探讨急性肝功能衰竭(ALF)大鼠肝脏线粒体解耦联蛋白(UCP)2的表达趋势及意义.方法 健康雄性SD大鼠36只,分为对照组和模型组,模型组冉分为6、12、24、36和48 h 5个亚组,每组6只.模型组腹腔内注射D-氨基半乳糖(D-Gal)和脂多糖(LPS)诱导大鼠ALF模型.采用HE染色,光学显微镜下观察肝组织损伤情况,采用RT-PCR和免疫组织化学检测不同时间点肝脏UCP2 mRNA转录及其蛋白表达,同时测定各时间点血清ALT、AST和肝组织丙二醛(MDA)的变化.各实验组问数值比较采用SNK检验.结果 模型组肝组织呈炎性细胞浸润和明显坏死的ALF特征;模型组ALT、AST、MDA值均明显高于对照组[(24.0±2.0)U/L,(82.3士16.9)U/L,(2.55±0.22)μmol/g],且造模24 h达高峰[(8346.7±1363.1)U/L,(9766.7±1274.1)U/L,(8.34±1.13)μmol/g;均P<0.05];UCP2蛋白和UCP2 mRNA在正常肝组织中几乎不表达,D-Gal和LPS处理后6 h表达均硅著增加(P<0.05),24 h表达最强,且模型组相邻时间点之间差异有统计学意义(P<0.05).结论 成功构建大鼠ALF模型,大鼠ALF时UCP2蛋白和UCP2mRNA的表达水平与肝损伤程度及氧化应激水平有关.     

晚期糖基化终末产物受体在急性坏死性胰腺炎大鼠中的表达

目的 观察急性坏死性胰腺炎(ANP)大鼠发病过程中胰腺组织及血清中晚期糖基化终末产物受体(the receptor for advanced glycation end products,RAGE)含量变化的规律.方法 64只雄性SD大鼠按完全随机法分为对照组,ANP 6、18、24、36、48、72、96 h组,每组8只.采用腹腔注射20％L-精氨酸250 mg/100 g体重2次、间隔1h方法制备ANP模型.对照组大鼠腹腔注射等容积生理盐水.胰腺组织行病理学检查并评分.检测腹水量、血清淀粉酶及RAGE浓度,实时PCR法检测胰腺组织RAGE mRNA表达.结果 ANP组胰腺病理损伤随时间延长逐渐加重;腹水量从6h的(1.98±0.64)ml增加到96h的(8.69 ±0.62) ml;血清淀粉酶浓度从造模后6h开始升高,18h达(5069.88±603.25)U/L,36 h时恢复正常.对照组大鼠血清RAGE浓度及胰腺组织RAGE mRNA表达量分别为(18.33±2.99) ng/ml和0.41 ±0.13.ANP组6h时两者开始升高,分别为(30.31±5.03)ng/ml和1.57±0.19,较对照组显著升高(P＜0.05);24 h组达峰值,分别为(105.41±21.31)ng/ml和4.23±0.73,较ANP其他时间点显著升高(P值均＜0.05);96 h下降至最低点,分别为(33.54±6.96) ng/ml和1.19±0.19,但仍高于对照组(P＜0.05).结论 血清RAGE浓度及胰腺组织RAGE mRNA表达量在ANP发生36 h内逐渐增加,随后下降,但始终高于正常值.     

趋化因子CXCL11及其受体CXCR3在重症急性胰腺炎相关肺损害中的作用

目的:制作大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)模型,检测不同时间点趋化因子CXCL11及其受体CXCR3在SAP肺组织中的动态变化,探讨他们在SAP肺功能损害过程中的作用.方法:48只SD大鼠,雌雄不限,随机分为2组:对照组(C组),SAP组(P组),每组24只.4%牛黄胆酸钠逆行胰胆管注射建立SAP大鼠模型,剂量为1mL/kg,C组打开腹腔后仅仅翻动胰腺组织数次.每组随机分为4个亚组,每个亚组6只.4个组分别在1、3、6、12h抽血、处死,留取组织标本.分别检测各不同时间点组的血清淀粉酶、肺湿干重比,胰腺组织、肺组织病理,免疫组织化学法检测肺CXCL11及CXCR3的表达,酶联免疫吸附试验(ELISA)检测血清中的CXCL11的水平.结果:P组各亚组血清淀粉酶值明显升高(P<0.01vsC组);肺湿干重比值:P组3、6、12h组较C组明显升高(P<0.05);胰腺组织、肺组织病理:3、6、12hP组肺组织损伤明显;免疫组织化学显示P组CXCL11与CXCR3蛋白表达较C组表达明显增强(P<0.05),ELISA显示:1、3、6、12hP组血清CXCL11蛋白较C组明显增高(P<0.01).结论:CXCL11/CXCR3可能参与大鼠SAP急性肺功能损害的发病过程.     

连翘对重症急性胰腺炎大鼠肝组织中NF-κB和Foxp3表达的影响

目的探讨核因子NF-κB和Foxp3在重症急性胰腺炎（SAP）肝损伤中的作用及连翘对其表达活性的影响。方法雄性Wistar大鼠80只,随机分成假手术组（SO组）、SAP组和干预组,其中干预组分连翘高、中、低剂量组和阳性对照组（PDTC）。牛磺胆酸钠溶液在胰胆管远端注射造模,SO和SAP组于术后3、6、12 h,干预组于术后12 h处死大鼠,分别留取标本。测各组血淀粉酶（AMY）、ALT及TNFα水平,鲎试剂法测血浆内毒素水平,流式细胞术测外周血Treg百分数,对胰腺及肝脏进行病理学检查及评分,RT-PCR法检测肝脏组织中NF-κBmRNA和Foxp3mRNA表达量。组间比较采用单因素方差分析,进一步进行多重比较,采用LSD法进行统计学处理,各指标间相关性分析采用直线相关分析。结果与SO组比较,SAP组中各项指标均随时间升高,于12 h达高峰。与SAP12 h组相比,干预组（大鼠死亡率为0）肝脏组织中的NF-κBmRNA和Foxp3mRNA表达明显降低（P〈0.01）,与Treg呈正相关（r=0.738,P〈0.01）。随连翘剂量增加,AMY、ALT及TNFα水平均明显降低,肝脏和胰腺组织炎症明显减轻,高剂量组和阳性对照组相比较无明显差异（P〉0.05）。结论 NF-κB的激活参与SAP肝损伤的发生,连翘能显著降低NF-κB的活性及肝脏组织中NF-κBmRNA和Foxp3mRNA的表达,减轻SAP肝损伤的严重程度。     

Dynamic changes of mitogen‐activated protein kinase signal transduction in rats with severe acute pancreatitis

OBJECTIVE: To investigate the dynamic changes of mitogen‐activated protein kinase (MAPK) signal transduction in rats with severe acute pancreatitis (SAP). METHODS: The SAP model was induced by infusing the bilio‐pancreatic duct of 56 Sprague‐Dawley rats with 5% sterile sodium taurocholate solution. The rats were randomly divided into seven groups: control group, 0.5 h postoperative group, 1 h group, 3 h group, 6 h group, 12 h group and 24 h group. Western blot analysis was used to determine the activities of p38 MAPK and c‐Jun N‐terminal kinase (JNK) in the pancreas and lungs. RESULTS: In the rats of the control group, basal p38MAPK activity could be detected but not that of JNK. After SAP was induced, the p38MAPK activity in the pancreas increased markedly and peaked at 3 h, but in the lung it peaked at 6 h. The p38MAPK activity in the pancreas and lungs was significantly higher than the basal activity at the 24 h time point. The activity of JNK was only increased at the 12 h point and was not detectable at 24 h. CONCLUSION: The MAPK signal transduction pathway, in particular p38MAPK, plays an important role in the pathogenesis of SAP.     

The mRNA expression patterns of tumor necrosis factor-α and TNFR-I in some vital organs after thermal injury

AIM: To investigate changes of tumor necrosis factor-α (TNFα) and TNFR-Ⅰ expression in vital organs and their significance in the pathogenesis of multiple organ damage associated with endogenous endotoxin following major burns.METHODS: Wistar rats subjected to a 35 % full-thickness scald injury were sacrificed at 12 h, 24 h, 48 h, and 72 h postburn, respectively. Meanwhile, eight rats were taken as normal controls. Tissue samples from liver, spleen, kidney,lung and intestine were collected to assay tissue endotoxin levels and measure TNF-α and TNFR-Ⅰ expression, In addition, blood samples were obtained for the determination of organ function parameters.RESULTS: Endotoxin levels in liver, spleen and lung increased markedly after thermal injury, with the highest level in liver. The gene expression of TNF-α in liver, lung and kidney was up-regulated after thermal injury, while the TNFR-Ⅰ mRNA expression in liver, lung, kidney and intestine was shown decreased throughout the observation period. Thus, the mRNA expression ratio of TNF-α to TNFRⅠ was significantly increased postburn, particularly in pulmonary tissue (67-fold). In addition, the significant correlations between the expression of TNFR-Ⅰ or the expression ratio of TNF-α/TNFR mRNA in liver tissue and serum aspartate aminotransferase levels were noted (P ＜0.05-0.01). Similar results were also obtained between pulmonary TNF-α mRNA expression and myeloperoxidase activities (P＜0.01), whereas there was a highly negative correlation between levels of renal TNFR-Ⅰ mRNA expression and serum creatinine.CONCLUSION: Burn injury could result in the translocation of gut-derived endotoxin that was mainly distributed in the liver, spleen and lung. The translocated endotoxin then made the expression of TNF-α and TNFR-Ⅰ mRNA up-regulated and down-regulated respectively in various organs, which might be involved in the pathogenesis of multiple organ damage following burns.     

Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis （SAP）.
METHODS： A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups （n = 32 in each group）： sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP （30 mg/kg） at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase （AST）, alanine arninotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） levels were measured. Lung wet-to-dry-weight （W/D） ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats.
RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios （8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological scores （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 vs 1 368 ± 271, P 〈 0.01）, ALT （446 ± 91 vs 653 ± 98, P 〈 0.01） and Cr （1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01） levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h （P 〈 0.01）.
CONCLUSION： Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome （MODS） in SAP patients.     

Influence of baicalin on TNF-α mRNA, caspase-3 and P-selectin expression in pancreatic tissue of rats with severe acute pancreatitis

Objective  

Baicalin reduces the severity of severe acute pancreatitis (SAP) in a rat model. This study was carried out to examine the effect of baicalin on TNF-α mRNA, caspase-3 and P-selectin protein expression in the pancreas of rats with SAP.