Thymulin,A Thymic Peptide,Prevents the Overproduction of Pro-Inflammatory Cytokines and Heat Shock Protein Hsp70 in Inflammation-Bearing Mice

The effects of synthetic analogue of peptide hormone thymulin, which is normally produced by thymic epithelial cells, on immune cells activity and blood cytokine profile had been studied in male NMRI mice with acute inflammation induced by injection of lipopolysaccharide from gram-negative bacteria (LPS, 250 μg/100 g of body weight). Inflammation induced by LPS resulted in accumulation of several plasma pro-inflammatory cytokines, IL-1β, IL-2, IL-6, TNF-α, interferon-γ, and also IL-10, anti-inflammatory cytokine. Thymulin previously injected in dose of 15 μg/100 g body weight, prevented the accumulation of proinflammatory cytokines in plasma. Thymulin also prevented LPS-induced up-regulation of production of several cytokines by spleen lymphocytes and peritoneal macrophages. Added in vitro, thymulin decreased the peak of TNF-α production in macrophages cultivated with LPS. In addition, thymulin lowered the peak of Hsp70 production induced by LPS treatment. The results indicate that thymulin having significant anti-inflammatory effect may be promising in clinical application.     

高迁移率族蛋白1参与脓毒症大鼠急性呼吸窘迫综合征时中性粒细胞的凋亡

目的 探究脓毒症大鼠急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)时高迁移率族蛋白1(high mobility group box 1,HMGB1)参与中性粒细胞(polymorphonuclear neutrophils,PMN)凋亡延迟的相关机制及正丁酸钠(sodium butyrate,SB)的干预效果. 方法 采用随机数字表法将90只健康成年雄性Sprague-Dawley(SD)大鼠随机分为正常对照组(NS组,6只)、内毒素(lipopolysaccharide,LPS)致伤组(LPS组,42只)、HMGB1抑制剂SB干预组(SB组,42只),LPS组、SB组又分为7个时相点(LPS致伤后0.5、1、2、6、12、24、48 h),每个时相点6只动物.LPS组,腹腔注射LPS 5 mg/kg;SB组,腹腔注射LPS 5 mg/kg后0.5 h静脉注射SB,每次剂量500 mg/kg;NS组,腹腔注射生理盐水1 ml.LPS组、SB组于LPS注射后各时点,颈静脉取血检查PMN,取血后左肺灌洗收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),取右肺中叶行HMGB1 mRNA检测;于LPS注射12h时点(NS组大鼠留取颈静脉血、收集BALF、取右肺中叶行HMGB1 mRNA检测),3组大鼠收集左肺BALF后,取右肺下叶检测肺组织湿/干重比(wet/dry weight ratio,W/D),取右肺上叶进行病理组织学检查;于24、48 h时点,LPS组、SB组取右肺下叶检测肺组织W/D、取右肺上叶进行病理组织学检查. 结果 与NS组比较,LPS组肺组织中HMGB1 mRNA表达量明显增高,24 h达最大值,差异有统计学意义(P＜0.05);SB组的HMGB1 mRNA表达量减少,差异有统计学意义(P＜0.05).LPS组BALF中凋亡早期PMN表达量与NS组类似,但凋亡晚期PMN变化则不同,LPS组外周血中凋亡晚期PMN细胞高于NS组(P＜0.05),LPS组BALF中凋亡晚期PMN细胞均低于NS组(P＜0.05).LPS 12 h组BALF的PMN百分比明显高于NS组[(49.1±6.8)、(2.7±0.5)],差异有统计学意义(P＜0.01).LPS组肺组织光镜下可见肺泡腔水肿,支气管壁中发现PMN浸润,肺泡壁毛细血管扩充血.LPS24 h组肺组织的W/D明显高于NS组[(6.71±0.12)、(4.18±0.26)],差异有统计学意义(P＜0.05).SB干预组的HMGB1 mRNA表达量减少,早期凋亡率类似,SB组的BALF晚期凋亡率高于同时点LPS组的BALF,SB外周血组晚期凋亡低于同时点LPS外周血组,差异有统计学意义(P＜0.05).SB组BALF的PMN百分比、肺组织病理损伤程度、W/D均低于LPS组,差异有统计学意义(P＜0.05). 结论 在大鼠ARDS中,HMGB1 mRNA表达较晚,但持续时间长,SB对HMGB1有潜在的治疗作用,HMGB1可能参与PMN凋亡机制的调节.     

Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy.     

内毒素在酒精性肝病肠损伤中的作用

目的探讨内毒素在酒精性肝病肠损伤中的作用。方法选择酒精性肝病患者15例和健康不饮酒者15例。采用ELISA法测定血清内毒素;采用分光光度法测定血清丙二醛。另将20只小鼠随机分为对照组和模型组,每组10只,分别喂饲Lieber-Decarli无酒精和含酒精液体饲料。10周后处死小鼠,检测血清内毒素,并进行肝脏和肠组织形态学观察。结果酒精性肝病组和对照组血清内毒素水平分别为0.52±0.54 Eu/L和0.47±0.34 Eu/L（P〈0.05）;酒精性肝病组和对照组血清丙二醛水平分别为5.6±5.0nmol/ml和3.7±3.4nmol/m（lP〉0.05）;模型组和对照组小鼠血清内毒素水平分别为0.38±0.05 Eu/L和0.13±0.02 Eu/L（P〈0.01）;模型组肝细胞明显脂肪变,结肠组织损伤病理学评分为10.3±1.3分,较对照组明显升高（4.8±1.2分,P=0.01）。结论酒精性肝病伴发了肠粘膜损伤,内毒素可能参与了发病过程。     

居室尘埃内毒素暴露与支气管哮喘及特应性疾病的关系

支气管哮喘(简称哮喘)与过敏性鼻炎等特应性疾病的患病率正不断上升,其发病的具体机制尚未完全清晰,主要是宿主免疫系统和环境相互作用的结果.内毒素是革兰阴性菌细胞壁上特有的结构,在外环境中内毒素几乎无处不在.内毒素对哮喘及特应性疾病而青是一把“双刃剑”,早期生活暴露于内毒素可能对疾病的发展具有保护作用;然而,暴露于高水平的内毒素环境不利于疾病的控制.     

血清降钙素原检测对于肾移植术后肺部感染的诊断价值

目的：与内毒素和C反应蛋白（ CRP）检测结果进行比较,探讨血清降钙素原（ PCT）检测在肾移植术后肺部感染诊断中的临床意义及其应用价值。方法回顾性分析2010年2月至2013年9月武汉大学移植医学中心98例肾移植术后并发肺部感染的受者临床资料。根据肺部感染的病原体诊断标准将受者分为细菌组（48例）和非细菌组（50例）,比较PCT、内毒素和CRP检测3种方法诊断肾移植术后细菌性肺部感染的灵敏度和特异度,比较3种方法对确诊肾移植术后并发细菌性肺部感染受者的阳性诊断结果。结果 PCT 检测灵敏度为95.8％,特异度为94．0％;内毒素检测灵敏度为77．1％,特异度为72．0％;CRP检测灵敏度为52．1％,特异度为58．0％。血清PCT检测细菌组受者阳性结果高于内毒素和CRP检测（χ2＝7.36,10．04, P均＜0．05）。结论血清PCT检测对于肾移植术后细菌性肺部感染的临床诊断价值高于内毒素和CRP,可作为肾移植受者是否并发细菌性肺部感染的优选诊断指标。     

A new approach using tissue alkaline phosphatase histochemistry to identify Crohn's disease

In the present study, we investigate intestinal alkaline phosphatase activity in mucosal biopsies in patients with inflammatory bowel disease. Crohn's disease influences the alkaline phosphatase activity in the intestine, increasing its activity. We present a histochemistry-based method for alkaline phosphatase that is useful for the identification of Crohn's disease and the differentiation of ulcerative colitis.     

Dose-related effects of direct hemoperfusion using a cytokine adsorbent column for the treatment of experimental endotoxemia

Objective To clarify the dose-related effects of direct hemoperfusion using a cytokine adsorbent column (CTR) on the mortality and inflammatory responses to endotoxin-induced shock in rats. Design Prospective and randomized study. Setting University research laboratory. Subjects Male Wistar rats. Interventions Forty-eight rats were injected intravenously with Escherichia coli endotoxin (15 mg/kg over 2 min), and then were randomly allocated to one of the following four groups (n = 12 per group): control group, treated without CTR for 120 min; quarter-dose treatment group, treated with CTR 0.25 ml for 120 min; half-dose treatment group, treated with CTR 0.50 ml; and full-dose treatment group, treated with CTR 1.0 ml. Measurements and results Hemodynamics and arterial blood gases were recorded, and mortality and plasma cytokine concentrations were calculated for the 8-h observation period. The mortality rates 8 h after endotoxin injection were 92%, 58%, 42% and 17% for the control column, quarter-dose, half-dose, and full-dose CTR groups, respectively. The increases in plasma cytokine concentrations were smaller in the half-dose and full-dose CTR treatment groups than in the endotoxemic group. Conclusions The present study showed that CTR treatment dose-dependently decreased the mortality rate and inhibited inflammatory responses in vivo. There was no supported funding in this study.     

Clostridium difficile infection as a cause of severe sepsis

Although colitis is often seen in critically ill patients who have received multiple broad-spectrum antibiotics, there are no reports describing severe sepsis as a result ofClostridium difficile infection. We describe three cases of severe sepsis with local intestinalClostridium difficile infection as the only identifiable etiology. The mechanism of severe sepsis may be a derangement of the gastrointestinal barrier function. This could result in absorption of microbes or endotoxin or activation of inflammatory cascades in the submucosa of the intestine or liver.     

川芎嗪对CCl4诱导的肝纤维化大鼠肝组织Nrf2/ARE信号通路的影响

目的：观察川芎嗪对四氯化碳诱导的肝纤维化大鼠肝组织Nrf2/ARE信号通路的影响,探讨川芎嗪治疗肝纤维化的作用机制。方法四氯化碳皮下注射制备大鼠肝纤维化模型,设立正常对照组、肝纤维化模型组和川芎嗪治疗组,川芎嗪治疗组在造模过程中每天给予盐酸川芎嗪注射液腹腔注射,6周后,乙醚麻醉,腹主动脉采血,产色基质偶氮法鲎试剂定量测定血浆内毒素;肝组织常规HE染色观察肝脏病变,天狼猩红胶原染色、肝组织羟脯氨酸含量测定评测肝纤维化程度;West-blotting法检测肝组织内Nrf2蛋白的表达, TBA法检测肝组织丙二醛（MDA）水平,酶显色定量分析法检测肝组织谷胱甘肽-S-转移酶（GST）含量。结果川芎嗪治疗组与肝纤维化模型组相比,肝损伤较轻,肝纤维化程度明显降低,血浆内毒素含量降低, Nrf2蛋白表达量增多,肝组织中MDA含量降低, GST的含量升高。结论川芎嗪的抗肝纤维化作用可能与其降低内毒素血症,激活肝内Nrf2/ARE抗氧化通路进而使得抗氧化酶GST等含量增加有关。