N-乙酰半胱氨酸对脂多糖诱导的急性肺损伤大鼠肺组织病理形态及TGF-β1表达的作用

目的:观察N-乙酰半胱氨酸(NAC)对脂多糖诱导的急性肺损伤大鼠肺组织形态及转化生长因子-β1表达的作用.方法:将30只SD大鼠随机分为正常对照组、模型组和NAC干预组3组,每组10只.模型组经舌下静脉注射5 mg/kg脂多糖制备大鼠急性肺损伤模型,NAC干预组在注射脂多糖后1h腹腔注射NAC(200 mg/kg),注入脂多糖后12h处死大鼠,取左叶肺组织,观察各组大鼠肺组织病理形态和TGF-β1的表达变化.结果:模型组肺泡间隔增宽,腔内有少许出血,渗出及炎性细胞浸润,肺间质充血水肿,有大量炎性细胞浸润,NAC干预组肺部炎性细胞浸润、渗出、出血较模型组明显减轻.模型组肺组织TGF-β1的表达较正常对照组明显增加(P＜0.05),NAC干预组TGF-β1的表达较模型组显著降低(P＜0.05),但与正常对照组比较差异无统计学意义.结论:NAC可显著减轻脂多糖诱导的大鼠急性肺损伤,这可能与其降低肺组织中TGF-β1的表达有关.     

大鼠吸入二氧化硫诱发气道神经源性炎症和气道高反应机制的探讨

目的：探讨大鼠吸入低浓度SO2后引起气道损伤以及气道反应性的变化与相关的病理生理机制。方法：SD雄性大鼠16只,随机分为2组（n=8）：对照组和SO2组。对照组暴露于正常空气中。SO2组暴露于含量为1．0mg／（m3·h）的SO2室内空气中,每天6h,连续3d,第4d测大鼠气道反应性,采集血清、收集支气管肺泡灌洗液（BALF）,留取肺组织。分别进行BALF细胞计数,测血清中P物质（SP）的含量,作肺组织病理切片行HE及SP免疫组化染色。结果：SO2组与对照组比较,大鼠的气道反应性增高（P〈0．01）,BALF中细胞总数明显升高（P〈0．01）;血清SP含量显著增加（P〈0．01）。肺组织病理切片UE染色显示SO2组支气管粘膜下有大量炎性细胞浸润;免疫组化染色提示SO2组SP免疫阳性神经纤维数量明显增加（P〈0．05）。结论：吸入SO2诱发大鼠出现气道高反应性,气道内感觉神经源性炎症是其重要的病理生理机制之一。     

当归注射液对急性肺栓塞大鼠P-选择素、抗心磷脂抗体的作用

目的:研究当归注射液对急性肺栓塞大鼠P-、E-选择素及抗心磷脂抗体(ACA)表达的影响。方法:SD大鼠按完全随机设计分为正常对照组(N组),血栓栓塞组(T组),当归治疗组(TA组),各组分1h、4h、8h3个时间点,分别用ELISA、免疫组化法检测大鼠P-、E-选择素及ACA水平。结果:肺组织HE染色N组大鼠肺内炎症细胞数较少。T组、TA组大鼠肺内炎症细胞数分别较N组升高(P0.05),且T组大鼠肺内炎症细胞数随时间延长逐渐增多;血浆ELISA法检测P-、E-选择素结果:T组分别较N组表达增高(P0.05);TA组分别较T组各相应时间点表达降低(P0.05);各组间大鼠血浆ACA的OD值无统计学意义(P0.05),但免疫组化显示TA组大鼠肺组织的P-,E-选择素及ACA表达均降低。结论:急性肺栓塞可引起大鼠肺部炎症细胞浸润,并可能通过P-、E-选择素及ACA释放增加,释放炎症介质加重肺损伤;中药当归注射液可能通过抑制P-、E-选择素及ACA的表达,减轻急性肺栓塞大鼠肺部炎症反应从而减少血栓形成。     

探讨接种时间和剂量对小鼠肺炎支原体肺炎模型建立的影响

目的 用不同时间和剂量建立BALB/c小鼠的肺炎支原体肺部感染模型,探索小鼠急性肺炎支原体感染的过程.方法 BALB/c小鼠随机分为Ⅰ、Ⅱ两组,Ⅰ组在0、1、2 d滴鼻接种肺炎支原体菌液3次,Ⅱ组在0 d滴鼻接种小剂量肺炎支原体菌液1次后于8、9 d再接种和Ⅰ组相同的肺炎支原体菌液2次,均设立不同剂量、批次的生理盐水对照组.全部实验动物在3～18 d内分批处死.所有小鼠均取肺组织做病理切片.以组织病理学评分来确定小鼠的肺部炎症反应程度.取肺组织匀浆及肺泡灌洗液(BALF)进行肺炎支原体培养做病原学检测.结果 接种后实验动物全部存活无死亡.实验组动物均出现不同程度的肺炎支原体肺炎样病理改变,组织病理学评分为1.5～14.3分,分别于第5、6天和第11天达到最高,平均分为4.9分;Ⅰ组实验组动物多呈轻、中度改变,Ⅱ组实验组动物多呈中、重度改变.所有实验组动物肺组织匀浆及BALF的肺炎支原体培养在接种后1月内先后出现阳性结果.对照组动物未出现明显肺部炎症改变,组织病理学评分为0～1分,肺炎支原体培养为阴性.结论 成功建立BALB/c小鼠的肺部肺炎支原体感染模型;组织病理学评分方法可用以评价肺部炎症反应的严重程度;不同接种时间和剂量所致的病变程度不同.     

早期戒烟大鼠肺病理及炎性介质变化

目的观察早期戒烟后大鼠肺组织病理及炎性介质表达变化规律。方法选用Wistar雄性大鼠80只,随机分为对照组及早期戒烟后0天、1周、2周、4周、6周、8周、12周组。采用酶联免疫吸附方法测定各组大鼠血清中IL-8的蛋白质含量,S-P免疫组化学方法检测肺组织NF-κB p65的表达,并光镜下观察HE染色切片、对大鼠气道炎症进行病理学评分。结果早期戒烟组大鼠可见气道上皮细胞纤毛发生粘连、倒伏,上皮细胞空泡变形、坏死、增生,炎症细胞浸润;其血清IL-8浓度、肺组织NF-κB的表达及气道炎症病理评分在戒烟后各时相点较未吸烟对照组明显升高,有统计学意义（P〈0.05）。早期戒烟组大鼠血清IL-8的浓度、肺组织NF-κB的表达及肺组织病理炎症评分在戒烟后略有上升、且在戒烟后8周达到高峰,但随后在戒烟12周时可见IL-8的浓度有下降趋势,肺组织病理炎症反应有所减轻。结论早期戒烟大鼠在戒烟早期虽可见炎症反应略有加重,但随戒烟时间延长,仍可见炎症反应有所减轻。因此,提倡及早且坚持戒烟。     

大鼠急性呼吸窘迫综合征动物模型的建立

目的　建立大鼠急性呼吸窘迫综合征动物模型 (ARDS)。方法　选取KM小鼠SD大鼠 (雌雄不限 ) ,分为正常对照组及百草枯组 ,小鼠按每公斤体重 10 0mg ,大鼠按每公斤体重 12 0mg一次灌胃给药。再分 2 4h、4 8h、72h组 ,小鼠每组 10只股动脉采血用于血气分析 ,取肺测定肺系数 ,全肺拍照进行对照 ,大鼠每组 10只取肺石腊包埋 ,病理切片。结果　①整体外观变化　随着给药时间延长 ,呼吸变得越来越困难、消瘦、咳嗽 ,2 4h后鼻腔有淡红色分泌物 ,食欲渐进性下降。②肺外观观察炎症渐进性发展 ,从正常粉红色发展到最后呈肝样变。③血气变化　随染毒时间延长 ,血液pH值逐渐降低 ,PaCO2 逐渐升高 ,PaO2 逐渐下降 ,肺系数逐渐增大 ,组间数据进行t检验p <0 0 1,差异有显著性。④病理切片观察肺部呈典型炎症病理变化过程 ,最终肺泡内形成典型透明膜。结论　百草枯染毒成功制造鼠ARDS模型。     

硫酸镁对脑源性肺损伤综合征的影响

目的探讨不同剂量的硫酸镁(MgSO4)对大鼠脑源性肺损伤后神经源性肺水肿、血浆炎性因子TNF-α及肺组织病理形态学变化的影响。方法将30只SD雄性大鼠按随机数字法分为假手术组(A组)、模型组(B组)及硫酸镁50mg/kg干预组(C组)、硫酸镁100mg/kg干预组(D组)、硫酸镁200mg/kg干预组(E组),每组6只。建立大鼠颅脑损伤模型后,硫酸镁干预组即刻按50mg/kg 25%MgSO4腹腔注射,C组注射1次、D组注射2次、E组注射4次,每8h注射1次。A组及B组的大鼠注射相同剂量生理盐水作对照,C组大鼠注射1次及D组大鼠注射2次MgSO4后给予注射相同剂量的生理盐水作对照,注射方法及间隔时间同E组。伤后48h测定大鼠肺组织含水量、血浆TNF-α浓度,肺组织常规HE染色,光镜观察肺组织病理形态学变化。结果大鼠颅脑创伤后肺组织含水量均高于假手术组,以C组最明显(P0.05),差异有统计学意义。B、C、D、E组大鼠之间肺组织含水量比较差异无统计学意义。B、C、D、E组大鼠TNF-α浓度均明显高于假手术组(P0.05),D组血浆TNF-α浓度明显低于B组(P0.05),E组血浆TNF-α浓度明显低于B组(P0.01),其他各组间差异无统计学意义。假手术组肺组织形态正常,肺血管无扩张,无炎症细胞浸润;B、C、D、E组与假手术组比较均可见终末支气管腔内充满炎症细胞,周围肺组织的肺泡腔内可见炎细胞浸润,肺血管扩张、充血。B、C、D、E组在炎症细胞浸润及肺毛细血管扩张方面无明显差异。结论脑外伤可导致脑源性肺损伤综合征,可导致神经源性肺水肿;硫酸镁可降低大鼠脑损伤后血浆TNF-α浓度,对肺水肿无明显影响。     

急性冷暴露对大鼠肺组织中促炎性因子表达的影响

目的:观察急性冷暴露大鼠肺部炎症反应及病理学损伤的变化情况,探讨冷应激对肺损伤的可能机制。方法:40只雄性Wistar大鼠随机分为5组(n=8),即对照组,-25℃0.5 h组、-25℃1 h组、-25℃2 h组和-25℃2.5h组。除对照组外,其他各组均在温度为-25℃、无风的低温舱内暴露。在冷暴露前后分别测定直肠温度,冷暴露后取材在光镜下观察肺组织学变化,酶联免疫吸附实验检测肺组织匀浆中促炎性因子的表达。结果:在急性冷暴露后,与对照组相比,-25℃1 h组、-25℃2 h组和-25℃2.5 h组暴露前后体心温度明显降低,其差值升高(P0.05)。-25℃2.5 h组肺组织学分析出现明显的炎性细胞浸润和肺泡内水肿液。-25℃1 h组、-25℃2 h组和-25℃2.5 h组肺组织匀浆中促炎性因子的浓度升高(P0.05)。结论:急性冷暴露后,肺组织出现明显的炎性细胞浸润和促炎性因子水平增加,从而导致肺组织损伤。     

非静脉曲张上消化道出血不同剂量奥美拉唑治疗的疗效比较

目的:比较不同剂量奥美拉唑治疗非静脉曲张上消化道出血的疗效。方法:选取2012年1月至2013年8月已被收治的符合标准的病例共256例非静脉曲张上消化道出血患者随机按知情同意原则分为治疗组(128例)和对照组(128例)两组,治疗组给予大剂量奥美拉唑治疗,对照组给予常规剂量奥美拉唑治疗,比较两组患者的临床疗效并记录分析两组患者治疗前后各观察指标有无统计学差异,并于治疗72小时后评估两组患者的胃内pH值及不良反应发生情况。结果:治疗组临床疗效优于对照组(P0.05),但是各指标改善情况、胃内Ph值及不良反应发生情况与对照组相近(P0.05)。结论:大剂量奥美拉唑治疗非静脉曲张上消化道出血有良好的临床疗效。     

小鼠烟雾吸入伤后肺组织中IKK／NF-KB表达的变化及意义

目的：探讨IKK／NF—kB调控的炎症反应在小鼠烟雾吸入伤后早期肺组织损伤中的作用。方法：建立小鼠烟雾吸入伤模型,将60只C57BL／6小鼠随机分成正常对照组,烟雾吸入性损伤后2h、8h和24h组,观察肺组织病理改变,免疫组织化学测定肺组织NF-kBp65,IKK1和IKK2的表达,酶联免疫吸附法（ELISA）测定肺组织TNF-α,IL-6和IL-1β含量。结果：病理切片显示正常对照组小鼠肺组织无明显异常,烟雾吸入后2h,8h,24h组肺部出现不同程度的炎细胞浸润、出血、水肿等;伤后2h组、8h组、24h组肺组织NF—KBp65、IKK1、IKK2免疫组化评分均高于正常组小鼠（P〈0．05）;肺组织TNFa、IL-6和IL-18含量在烟雾吸入后2h、8h、24h均高于正常对照组（P〈0．05）。结论：NF—KB信号通路与烟雾吸入伤早期肺内大量炎症因子的释放密切相关,可能是导致伤后肺组织病理性损伤的重要因素。     

Interactions between gastric microbiota and metabolites in gastric cancer

The development and progression of gastric cancer (GC) is greatly influenced by gastric microbiota and their metabolites. Here, we characterized the gastric microbiome and metabolome profiles of 37 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and ultrahigh performance liquid chromatography tandem mass spectrometry, respectively. Microbial diversity and richness were higher in GC tumor tissues than in non-tumor tissues. The abundance of Helicobacter was increased in non-tumor tissues, while the abundance of Lactobacillus, Streptococcus, Bacteroides, Prevotella, and 6 additional genera was increased in the tumor tissues. The untargeted metabolome analysis revealed 150 discriminative metabolites, among which the relative abundance of the amino acids, carbohydrates and carbohydrate conjugates, glycerophospholipids, and nucleosides was higher in tumor tissues compared to non-tumor tissues. The targeted metabolome analysis further demonstrated that the combination of 1-methylnicotinamide and N-acetyl-D-glucosamine-6-phosphate could serve as a robust biomarker for distinction between GC tumors and non-tumor tissues. Correlation analysis revealed that Helicobacter and Lactobacillus were negatively and positively correlated with the majority of differential metabolites in the classes of amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids, respectively, suggesting that Helicobacter and Lactobacillus might play a role in degradation and synthesis of the majority of differential metabolites in these classes, respectively. Acinetobacter, Comamonas, Faecalibacterium, Sphingomonas, and Streptococcus were also significantly correlated with many differential amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids. In conclusion, the differences in metabolome profiles between GC tumor and matched non-tumor tissues may be partly due to the collective activities of Helicobacter, Lactobacillus, and other bacteria, which eventually affects GC carcinogenesis and progression.Subject terms: Cancer metabolism, Gastrointestinal cancer     

Apoptosis in gastric mucosa with stress-induced gastric ulcers.

The maintenance of gastric mucosal integrity depends upon the interplay between epithelial cell proliferation and apoptosis (programmed cell death). The Bcl-2 family of proteins plays a central role in the regulation of apoptotic cell death by suppressing the apoptosis while some others such as Bax proteins promote this process. Stress-induced gastric ulcerations are accompanied by the fall in gastric mucosal cell proliferation but little is known about the influence of the stress on the apoptosis in gastric mucosa. In the present study, the gastric epithelial apoptosis was determined by means of expression of Bax and Bcl-2 mRNA in the gastric mucosa following acute stress. Wistar rats were exposed to mild water immersion and restraint stress (WRS) for 3.5 h and then sacrificed at 0, 2, 4, 6, 12 and 24 h after the termination of WRS. At each time interval after WRS, the gastric blood flow (GBF) and the proliferating cell nuclear antigen (PCNA) labeling were determined. The apoptosis rate in the gastric mucosa was determined by the terminal deoxynucleotidyl transferase (TDT) mediated 2-deoxyuridine 5-triphosphate (dUTP)-biotin nick end-labeling (TUNEL) staining method and the expression of Bax and Bcl-2 mRNA was analyzed by RT-PCR and southern blot hybridization. WRS produced multiple erosions accompanied by the fall in GBF and PCNA index and by a dramatic enhancement in gastric epithelial apoptosis rate reaching maximum at 4 h after exposure to WRS. Following 6 and 12 h after the end of WRS the apoptotis declined but even 24 h after WRS it failed to reach the value recorded in intact gastric mucosa. The PCNA index was still significantly inhibited at 2 h after WRS but then showed significant rise at 6 and 12 h to reach at 24 h after WRS, the level similar to that measured in intact gastric mucosa. The expression of Bax mRNA was detected in intact gastric mucosa and gradually increased in first 4 h after WRS to decline at 24 h to the level not significantly different from that observed in the intact mucosa. In contrast, the expression of Bcl-2 mRNA was almost undetectable during first 4 h but showed strong signal at 6 and 12 h to decline to the control level 24 h after WRS. We conclude that: 1. Healing of WRS lesions involves an increase in GBF and mucosal cell proliferation and 2. The enhancement in gastric epithelial apoptosis accompanies the mucosal damage induced by stress and this appears to be triggered by the shift from the cell death effector Bax to the cell death repressor Bcl-2 protein.     

Spontaneous rupture of giant gastric stromal tumor into gastric lumen

BACKGROUND: Gastrointestinal stromal tumors (GIST) constitute a large majority of mesenchymal tumors of the gastrointestinal (GI) tract, which express the c-kit proto-oncogene protein, a cell membrane receptor with tyrosine kinase activity. GI stromal tumors of the stomach are usually associated with bleeding, abdominal pain or a palpable mass. CASE PRESENTATION: A 75-year-old male presented with upper abdominal pain and palpable mass. Computed tomographic (CT) scan of the abdomen showed a large mass arising in the posterior aspect of fundus, body, and greater curvature of the stomach. Second day after the admission, there was significant reduction in the size of the tumor, clinically as well as radiologically. Endoscopic biopsy showed large bulge in fundus and corpus of the stomach posteriorly with an opening in the posterior part of the corpus, and biopsy from the edge of the opening reveled GIST. Patient underwent curative resection. CONCLUSION: Spontaneous ruptured of giant gastric stromal tumor is very rare presentation of stomach GIST. Thorough clinical examination and timely investigation can diagnose rare complication.