中性粒细胞弹性蛋白酶在重症急性胰腺炎并急性肺损伤发病中的表达和意义

目的探讨中性粒细胞弹性蛋白酶(NE)在重症急性胰腺炎并急性肺损伤(SAP-ALI)发病过程中的作用和意义。方法健康SD大鼠60只,随机分成3组:假手术组(n=18)、SAP-ALI组(n=22)、NE处理组(n=20)。ELISA法测定血清NE、TNF-α、IL-1β含量,RT-PCR法检测肺组织中NE的变化,Western blot检测肺组织中NE的表达,ELISA法检测肺泡灌洗液(BALF)和血清中的NE的含量变化,同时观察肺和胰腺组织湿/干质量比和病理形态学变化。结果 NE处理组肺组织、BALF和血清NE含量均较假手术组和SAP-ALI组大鼠明显增加(P<0.05或P<0.01),血清TNF-α、IL-1β含量也明显增加(P<0.05)。结论中性粒细胞的大量激活及其NE、TNF-α、IL-1β的过度释放参与了SAP-ALI的发病过程。     

Therapeutic elastase inhibition by alpha-1-antitrypsin gene transfer limits neointima formation in normal rabbits

PURPOSE: Alpha-1-antitrypsin (AAT) is the major circulating elastase inhibitor. Deficiency of elastase inhibition leads to emphysema and vascular abnormalities including accelerated neointima. Because recent evidence suggests that tissue AAT levels determine inhibitory function, the authors hypothesize that local tissue-based expression of AAT limits elastase activity sufficiently to guide arterial response to injury. MATERIALS AND METHODS: Rabbit common femoral arteries were injured by mechanical overdilation and treated with buffer, viral control, or an adenovirus expressing AAT (Ad/AAT). After 3 and 28 days, intima-to-media (I/M) ratios were evaluated. Additionally, early changes in elastase inhibition potential (3 d), extracellular elastin and collagen content (3 d), and local macrophage and neutrophil infiltration (7 d) were determined. RESULTS: Ad/AAT significantly decreased neointima formation after mechanical dilation injury after 28 days: buffer controls exhibited mean I/M ratios of 0.76 +/- 0.06, whereas viral controls reached 0.77 +/- 0.09; in contrast, Ad/AAT reduced I/M ratios to 0.44 +/- 0.06. Both early elastin and collagen content were preserved in the Ad/AAT group relative to controls. The Ad/AAT group also reversed the local inflammation that characterized viral controls. CONCLUSIONS: This strategy demonstrates that local increases in elastase inhibition potential promote a neointima-resistant small-caliber artery, which may offer new promise in management of patients undergoing angioplasty.     

去白细胞血预充对体外循环肺的保护作用

目的：体外循环前去除预充血液中的白细胞,探讨其对体外循环肺保护作用。方法：50例≤10岁的室间隔缺损患儿随机分成实验组和对照组,实验组用去白细胞血预充,对照组用库存全血预充。测定围术期血浆中性粒细胞弹性蛋白酶（NE）、肿瘤坏死因子-α（TNF-α）、IL-6、白介素-8含量;氧合指数（OI）、肺泡-动脉血氧分压差（P（A-a）O2）和呼吸指数（RI）及术后呼吸机通气时间。结果：实验组术后机械通气时间,体外循环后血浆中NE、TNF-α、IL-6和IL-8浓度,肺泡动脉血氧分压差和RI低于对照组（P〈0.05,P〈0.01）,OI在体外循环后高于对照组（P〈0.05）。结论：去白细胞血预充能减少中性粒细胞蛋白酶、TNF-α、IL-6和IL-8的含量,改善术后肺换气功能,缩短术后的机械通气时间,具有良好的肺保护作用。     

Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases.     

硫化氢对大鼠舱室内肢体爆炸伤后肺损伤的作用

目的研究外源性硫化氢（H2S）对大鼠舱室内肢体爆炸伤后肺损伤的作用,探讨H2S相关药物在舱室战伤救治中的应用价值。方法80mg二硝基重氮酚（DDNP）纸制点爆源紧贴大鼠左后肢跗关节内侧于舱室内引爆致伤。大鼠随机分为单纯致伤组（E组：n=32）、致伤＋硫氢化钠（NaHS）组（S组：5mg／kgNaHS,ip;n=16）和正常对照组（C组：n=8）。收集大鼠肺组织和血标本。测定大鼠胸部承受冲击波压力,测定肺组织胱硫醚-γ-裂解酶（CSE）活力和血浆H2S浓度、TNF-α、IL-6、IL-10浓度和肺含水量,观察肺组织病理学变化。结果爆炸致伤后大鼠肺组织CSE活力和血浆H,s浓度显著下降（P〈0．05）,TNF-α、IL-6、IL-10浓度及肺含水量较正常对照大鼠相应值显著升高（P〈0．05或P〈0．01）,肺出血、水肿、炎细胞浸润和肺泡结构破坏明显;而早期给予5mg／kgNaHS后伤鼠肺组织TNF-α、IL-6、IL-10浓度及肺含水量显著降低（P〈0．05,VSE组）,肺出血、水肿和炎细胞浸润程度明显减轻。结论大鼠舱室内肢体爆炸伤可引起严重的肺损伤;而早期适量给予H2S则可明显抑制肺炎性反应水平,减轻爆炸伤后肺损伤。     

药物性肝损害的多层螺旋CT影像表现

目的 探讨药物性肝损伤的MSCT表现.方法 回顾性分析2008年5月至2010年1月间经临床及病理证实的40例药物性肝损伤患者的MSCT影像及临床资料,总结其影像表现特征.结果 药物性肝损伤的MSCT影像表现主要有3种类型.(1)弥漫性肝脏损害2例:平扫肝脏密度均匀性减低,增强扫描肝实质轻度均匀强化.病理表现为肝细胞脂肪变性;混合炎性细胞浸润,点状坏死,毛细胆管淤胆.(2)灶性肝脏损害6例:肝内大片或多发小片状坏死灶5例.平扫肝脏密度不均匀,病变区为低密度改变;增强后病变区强化,特别是静脉期与平扫图像比较呈反转表现.另1例病程20 d的移植肝显示肝内弥漫的结节样再生.CT平扫可见肝内弥漫分布的稍高密度结节灶,增强后动脉期病灶强化,静脉期及延迟期近似于肝实质密度.5例患者病理表现为肝细胞片状及桥接坏死,大量混合炎性细胞浸润;1例重度淤胆,假小叶形成,肝细胞羽毛变性.(3)肝硬化表现2例:平扫肝脏表面呈结节状,肝叶比例失调,肝裂增宽.增强后肝脏强化一致,同时伴有脾大、腹水、侧支循环.病理为纤维组织增生,点状坏死和毛细胆管淤胆.结论 药物性肝损伤的MSCT影像表现具有一定的特征性,对临床诊断具有重要的参考价值.     

A study of neutrophil as a morphological marker of death from hemorrhagic shock in forensic practice cases

Excessive autolytic inflammation accompanied by dysfunction of “shock organs” is recognized as arising from hemorrhagic shock due to the promotion of endovascular recruitment of neutrophils. Here, activated neutrophils in the organs of autopsy cases were evaluated as a marker of death from hemorrhagic shock. Morphologically-determined injury to the heart, lung, liver, and kidney was investigated in death from five major causes: hemorrhagic shock, head injury, exsanguination, asphyxia, and drowning. The frequency of activated neutrophils was assessed by immunohistochemical staining. When the antemortem interval was less than 2 h, it was found that neither morphological damage nor neutrophil frequencies were significantly different after death due to any of these 5 causes. In contrast, at longer antemortem intervals up to 8 h, the frequency of neutrophils in hemorrhagic shock was significantly greater than in head injury, whereas the degree of morphological damage was no different. Thus, the appearance of activated neutrophils in the primary organs could be useful to identify death caused by hemorrhagic shock after longer antemortem intervals.     

氧化应激在中暑大鼠急性肝损伤中的作用及机制研究

目的 探讨氧化应激在中暑急性肝损伤发生中的作用及其可能机制.方法 32只大鼠按随机数字表法分为4组:假加热正常对照组(Sham组)、中暑组(HS组)、假加热N-乙酰半胱氨酸治疗组(Sham-NAC组)以及中暑NAC治疗组(HS-NAC组),每组8只.通过人工气候舱制备中暑大鼠模型,监测大鼠直肠温度(Tr)、脉率(HR)、收缩压(SBP).记录中暑发生的时间.于中暑开始后12h处死大鼠,测定大鼠血清丙氨酸氨基转移酶(ALT)和总胆红素(TBIL)水平,以及肝脏组织匀浆IL-6、IL-1β、TNF-α、丙二醛(MDA)、总超氧化物歧化酶(T-SOD)和谷胱甘肽(GSH)等指标的变化,组织学观察肝脏氧自由基(ROS)含量、中性粒细胞浸润以及病理损伤情况.结果 中暑发生时HS-NAC组与HS组Tr、HR、SBP、中暑发生时间等比较差异无统计学意义(P＞0.05),但HS-NAC组的生存时间与HS组相比明显延长,差异有统计学意义(P=0.039).中暑发生后12h,HS组肝组织匀浆中ROS和MDA含量及血清ALT和TBIL水平较其他3组明显升高(P=0.000),肝组织匀浆中T-SOD和GSH含量较其他3组明显下降(P=0.000).病理观察显示HS-NAC组肝损伤较HS组减轻(P=0.000).HS组肝脏中性粒细胞浸润水平及IL-6、IL-1β、TNF-α浓度均明显高于HS-NAC组(P=0.000).结论 氧化应激在中暑肝损伤中起重要作用,其机制可能与直接细胞毒和介导炎症反应有关.     

Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue.

(11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. METHODS: Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. RESULTS: NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma. CONCLUSION: In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.     

Toluene inhalation induced 8-hydroxy-2'-deoxyguanosine formation as the peroxidative degeneration in rat organs

The effect of toluene inhalation on oxidative damage in rat organs was examined. Male Wistar rats was inhaled toluene (1500 ppm for 4 h a day) for 7 days. Quantitatively and immunohistochemically, oxidative DNA damage, lipid peroxide (LPO) and superoxide dismutase (SOD) were examined. As a marker of the oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG) immunoreactivity increased in the lung, liver and kidney. The amount of 8-OH-dG also increased in liver and kidney significantly. In the testis, the amount of 8-H-dG did not increase, however 8-OH-dG immunoreactivity enhanced in the spermatogonia. SOD immunoreactivity increased in the lung, liver and kidney. However, 4-hydroxy-nonenal immunoreactivity and the amount of LPO did not change in each organ. Thus, oxidative damage by toluene is mainly DNA damage, especially, the oxidative DNA damage observed in the lung, liver and kidney for the increase of the immunoreactivity and amount of 8-OH-dG.     

儿童郎格尔汉斯细胞增生症的CT表现（附13例分析 ）

目的 探讨CT对郎格尔汉斯细胞组织细胞增生症（Langerhans cell histocytosis,LCH)造成多脏器损害诊断的价值及限度。方法 分析13例经临床、实验室、病理检查确诊的LCH的CT表现。局限性LCH4例,广泛性LCH9例。全部病例均行颅脑、胸部、肝、脾CT平扫检查,4例行增强检查。结果 男性多于女性,颅穹隆骨破坏依次为颞骨8例、顶骨3例、枕骨2例、额骨1例。CT发现早期骨破坏敏感性高。肿块变化可反映病变由活跃增殖到静止消退的病理过程。下丘脑－垂体轴侵犯影像表现晚于临床。CT可显著LCH不同阶段的肺损害。结论 LCH各脏器损害的影像学表现缺乏特异性。好发部位的典型CT表现可提示诊断,同时对辅助LCH分型、确定治疗方案、估计预后有一定价值。     

儿童郎格尔汉斯细胞组织细胞增生症的CT表现(附13例分析)

目的　探讨CT对郎格尔汉斯细胞组织细胞增生症(Langerhans cell histiocytosis,LCH)造成多脏器损害诊断的价值及限度。方法　分析13例经临床、实验室、病理检查确诊的LCH的CT表现。局限性LCH 4例,广泛性LCH 9例。全部病例均行颅脑、胸部、肝、脾CT平扫检查,4例行增强检查。结果　男性多于女性,颅穹隆骨破坏依次为颞骨8例、顶骨3例、枕骨2例、额骨1例。CT发现早期骨破坏敏感性高。肿块变化可反映病变由活跃增殖到静止消退的病理过程。下丘脑-垂体轴侵犯影像表现晚于临床。CT可显示LCH不同阶段的肺损害。结论　LCH各脏器损害的影像学表现缺乏特异性。好发部位的典型CT表现可提示诊断,同时对辅助LCH分型、确定治疗方案、估计预后有一定价值。     

Chronic granulomatous disease of childhood. Report of two cases with unusual involvement of the gastric antrum and spleen

Chronic granulomatous disease (CGD) of childhood is a rare entity. The disease is characterized by recurrent infections with granuloma and abscess formation caused by an inherited defective neutrophil leukocyte function. The most common sites of involvement are the lungs, lymph nodes, skin, liver, spleen and bones. Rarely are other organs affected. Two children with CGD are presented. The children were cousins, the older with bone, lung and splenic involvement. The younger had circumferential thickening of the gastric antrum. Some of the lesions were well delineated with ultrasonography. The unusual gastric antrum wall and focal splenic involvement in this disease are emphasized.     

Histological demonstration of haemosiderin deposits in lungs and liver from victims of chronic physical child abuse

In the context of chronic physical child abuse, two entities have been described based on macroscopical and radiological criteria: the battered baby syndrome and the shaken baby syndrome. However, in some autopsy cases, clinico-radiological information may not be available. In these cases, histological examinations are necessary to look for sequelae of repeated haemorrhages, particularly in organs likely to have suffered traumatisms such as the lungs, or in organs belonging to the mononucleated macrophage resorption system, such as the liver and the spleen. We examined a series of 15 young children who died from proven chronic child abuse and compared them with 15 sex and age-matched control subjects who died from natural causes with no history of child abuse. Using Perl’s stain for iron, we identified haemosiderin deposits in pulmonary, hepatic and splenic samples and the deposits were evaluated qualitatively and quantitatively. Haemosiderin deposits were significantly (P < 0.001) more abundant in the lungs and liver of the chronic abuse victims than in those of the control subjects. However, they were not significantly more abundant in the spleens of child abuse victims than in controls. We conclude that haemosiderin deposits in lungs and liver could be proposed as a marker for chronic physical child abuse. This study stresses the importance of systematic histological examination to look for pulmonary and hepatic haemosiderin deposits in cases in which chronic child abuse is suspected. Received: 30 September 1998 / Received in revised form: 21 December 1998     

白血病髓外浸润的CT、MRI表现

目的:对比分析白血病髓外浸润的CT、MRI表现,探讨CT、MRI对本病的诊断价值。方法:回顾性分析我院2011年3月至2013年10月16例经病理确诊白血病髓外浸润患者的临床和影像资料,探讨CT、MRI表现特点。结果:16例中,脑内及眼眶浸润4例,脑内病变累及颞叶、额叶、顶叶;单纯肺部浸润2例,累及上叶、下叶;肝脾同时浸润6例,均为肝、脾内多灶性病变;肺肝同时浸润2例;骶椎管内外受累2例。肺部病变为多样性,肝脏病变为弥漫性结节性,骶椎管内外受累病变为骨质破坏并软组织肿块。结论:CT、MRI可充分显示白血病髓外浸润所累及器官,但缺乏特征性,诊断仍需结合临床表现、病史、组织学、免疫生化检查等。     

严重急性呼吸综合征X线表现初步分析

目的初步分析严重急性呼吸综合征(SABS)的X线表现，为其早期诊断提供参考。资料与方法回顾分析2003年3月20日-4月28日经临床综合诊断为SABS患者82例的胸部X线表现。结果82例SABS患者，除2例儿童肺部无明显异常外，其余80例均有改变，其表现主要为肺野透亮度减低、大小不一的斑片状、球形阴影的肺实质漫润，以及肺内间质漫润为主的肺纹理异常、索条影、网状影、结节影。结论胸部X线检查为临床诊断和治疗SABS病提供了有力的依据。     

Efficient inhibition of in-stent restenosis by controlled stent-based inhibition of elastase: a pilot study

PURPOSE: It is proposed that local elastase inhibition could suppress the extracellular matrix (ECM) degradation and subsequent smooth muscle cell migration and limit subsequent in-stent restenosis. This study evaluated the effect of stent-based controlled elastase inhibition on restenosis after stent implantation in a rabbit model. MATERIALS AND METHODS: Biodegradable microspheres containing the potent elastase inhibitor alpha-1-antitrypsin (AAT) were prepared. Daily release of AAT from the microspheres was confirmed in vitro. The microspheres were loaded into stents with an abluminal polymer reservoir. Implantation of the stent with AAT microspheres and blank microspheres (control) was performed in the abdominal aortae of six rabbits in each group. After stent deployment, all stents were overdilated to 125% diameter. Stent-implanted arteries were harvested after 7 days (n = 3 each) or 28 days (n = 3 each). To assess the effect of local delivery of AAT, elastase activity and elastin content of the stent-implanted aortae were analyzed. As an endpoint, intima-to-media (I/M) ratio was determined in the 7-day and 28-day specimens. RESULTS: Significant inhibition of elastase was confirmed in treated vessels versus controls at 7 days after stent implantation (P < .05). This reduction in elastase activity was sufficient to afford early and late reduction of in-stent neointima. Plaque progression in the 28-day specimens decreased to 67% with elastase inhibition relative to controls (P < .05). CONCLUSION: Stent-based controlled release of elastase inhibitor may significantly reduce ECM degradation and might limit in-stent restenosis.     

The gene expression of cytokines and chemokines induced by tourniquet shock in mice

Traumatic shock is one of the major fields in forensic pathology, but its mechanism remains elusive from the pathophysiological aspects. Tourniquet shock has been established as one of the animal models of traumatic shock, and we examined the gene expression of cytokines and chemokines in the lung and liver in tourniquet shock using mice. Tourniquet was conducted by the application of elastic bands with five turns at both the thighs as high as possible for 2 h, followed by reperfusion. In this procedure, more than 90% mice died within 48 h after reperfusion. Serum hepatic transaminase and hematocrit values significantly increased at 2 h after reperfusion, and their elevation was still evident after 10 h. Histopathologically, hemorrhages, congestion and leukocyte recruitment were observed in the lung and liver specimens after 6 h of reperfusion. Immunohistochemical analysis with anti-myeloperoxidase antibody demonstrated a massive neutrophil infiltration in the lung and liver at 2 h or more after reperfusion. RT-PCR analyses demonstrated that the gene expression of interleukin-1beta, tumor necrosis factor-alpha, monocytes chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-2, KC and vascular endothelial adhesion molecule-1 was most enhanced in the lung and liver at 2 h after reperfusion. Thus, the gene expression of cytokines and chemokines is presumed to be closely related with the onset of tourniquet shock. From the forensic aspects, these cytokines and chemokines are considered to be useful markers for the early diagnosis of tourniquet shock.