丹参辅助治疗高脂血症急性胰腺炎

目的:探讨丹参辅助治疗高脂血症急性胰腺炎的效果。方法:选取63例高脂血症急性胰腺炎患者,分为对照组31例常规治疗,治疗组32例加用丹参辅助治疗,对两组临床症状、实验室检查指标及治疗效果进行比较分析。结果:治疗组恶心呕吐缓解时间、腹痛腹胀缓解时间及平均住院天数均较对照组均明显缩短(P0.05);两组较治疗前白细胞水平、血小板水平、凝血酶原时间均显著降低(P0.05),但两组间无明显差异(P0.05);出院时治疗组的血细胞比容、D-二聚体、C反应蛋白、血钙、甘油三酯分别为(44.2±3.7)%、(0.3±0.1)mg/L、(21.5±5.8)mg/L、(2.6±0.2)mmol/L、(1.8±0.6)mmol/L,与对照组比较D-二聚体、C-反应蛋白、甘油三酯指标明显降低(P0.05),血细胞比容、血钙明显升高(P0.05)。结论:丹参辅助治疗高脂血症急性胰腺炎,通过改善微循环、抑制钙超载及抑制炎症反应,使高脂血症急性胰腺炎患者症状明显改善,缩短住院时间。     

糖原合酶激酶3β在轻型/重症急性胰腺炎细胞模型中的表达

目的 探讨糖原合酶激酶3β(GSK3β)在轻型/重症急性胰腺炎发病中的表达及作用方法 采用单独雨蛙素、雨蛙素联合脂多糖刺激分别构建轻型急性胰腺炎(MAP)和重症急性胰腺炎(SAP)的细胞模型,分别在2、4、8、12、24 h收集细胞培养基上清,酶联免疫吸附测定(ELISA)检测淀粉酶、脂肪酶、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的表达变化,流式细胞术检测细胞凋亡率及坏死率,实时荧光定量聚合酶链反应(FQ-PCR)检测GSK3β及半胱氨酸天冬氨酸蛋白酶(Caspase)-3、-8、-9 mRNA表达变化.结果 雨蛙素组和雨蛙素+脂多糖组各时间点淀粉酶、脂肪酶、TNF-α、IL-6较对照组均增高,且在大多数时间点,雨蛙素+脂多糖组组比雨蛙素组水平更高,开始上调时间相同或更早(P＜0.05).刺激24 h后,雨蛙素组凋亡率[(19.2±0.9)％]显著高于雨蛙素+脂多糖组[(10.2±0.5)％,P ＜0.05].雨蛙素组坏死率[(5.8±0.3)％]显著低于雨蛙素+脂多糖组[(13.6±0.7)％,P＜0.05].SAP组的坏死/凋亡比值是MAP组的5倍.GSK3β的mRNA水平在雨蛙素组中是2h短暂下调[相对表达量为(0.5±0.1)倍]后于8h显著上升[相对表达量为(3.0±1.1)倍,P ＜0.05],然后又逐步下降;而在雨蛙素+脂多糖组中则是是8h才缓慢上调[相对表达量为(1.8±0.6)倍,P＜0.05],至24 h达到高峰[相对表达量为(3.6±0.3)倍,P＜0.05].GSK3β和Caspase-3 mRNA水平均有升高,但差异无统计学意义(P＞0.05).结论 采用单独雨蛙素、雨蛙素联合脂多糖刺激分别建立MAP和SAP细胞模型可行;GSK3β在MAP和SAP中可能通过促进腺泡细胞凋亡来起作用.     

硼替佐米调控泛素蛋白酶活性治疗小鼠重症急性胰腺炎的作用及其机制

目的 探讨蛋白酶体抑制剂硼替佐米调控泛素蛋白酶活性治疗小鼠重症急性胰腺炎的作用机制.方法 采用连续7次腹内注射雨蛙素(每次间隔1h)及脂多糖制作小鼠重症急性胰腺炎模型,将60只TCR雌性小鼠随机分为PS-341治疗组(注射脂多糖前0.5h腹内注射0.5 mg/kgPS-341)、模型对照组[注射脂多糖前0.5h腹内注射50％二甲基亚砜(DMSO)]、空白对照组(生理盐水制模).最后1次注射雨蛙素后2h麻醉小鼠,自右颈静脉取血检测血淀粉酶、白细胞介素(IL)-1β和IL-6.光镜下观察小鼠胰腺、肺脏的病理形态,应用TUNEL法检测细胞凋亡,免疫印迹法(Western blot)检测胰腺组织中IKBα的表达,电泳迁移率实验(EMSA)测定核因子(NF)-KB活性.结果 雨蛙素联合脂多糖小鼠腹腔内注射后,小鼠胰腺呈现典型的出血、坏死病理表现,血清淀粉酶、IL-1β、IL-6的表达值分别为:7663.0±559.0、229.6 -41.0、51.6±10.3,都较空白对照组(1732.0±540.0、9.3±1.8、4.3±1.0)明显升高(P＜0.05).PS-341治疗后,胰腺组织中I-κB降解自3.37±0.46减少至2.48±0.57,NF-κB活性自7.82±0.45下降至2.13±0.26,胰腺和肺脏出血、坏死和炎细胞浸润明显减轻;血清淀粉酶、IL-1β、IL-6的表达(2927.0±524.0、153.3±30.4、37.9±7.5)都较对照组显著下降;而胰腺组织中细胞凋亡明显增多(4.35±0.19增至7.91±0.26,P＜0.05).结论 PS-341可以抑制胰腺内NF-KB活化、促进细胞凋亡,从而减轻胰腺损伤,对小鼠重症胰腺炎有一定的治疗作用.     

高压氧对兔耳创面模型早期瘢痕组织形成的影响

目的 通过观察高压氧对兔耳创面愈合及瘢痕形成的影响,以探讨在临床中应用高压氧防治早期瘢痕的可行性.方法 选取新西兰白兔16只建立兔耳增生性瘢痕模型,每只兔左耳4个创面,右耳4个创面,共128个,随机分为高压氧组与对照组2组,每组8只,64个创面.高压氧组术后立即开始高压氧处理,2个大气压,吸氧60 min,每日1次,疗程以创面愈合为准.期间观察记录创面愈合情况以及兔耳瘢痕大小、厚度、颜色、硬度.待创面全部愈合后,切取创面进行HE染色,Masson染色和苦味酸天狼星红染色,行病理学观察、检测及分析.结果 高压氧组愈合时间为(16.7±1.8)d;对照组为(20.2±2.3)d,差异有统计学意义(P＜0.05).高压氧组瘢痕增生发生率较对照组低,实验组发生率为(38/64,59.4％),对照组发生率为(52/64,81.2％),差异有统计学意义(P＜0.05).光镜下观察,高压氧组真皮层较对照组薄,成纤维细胞数量较少,胶原较疏松,排列较整齐,胶原结节和漩涡状结构少.瘢痕增生指数,高压氧组为3.48±0.94,对照组为4.65 ±0.76,差异有统计学意义(P＜0.01).成纤维细胞密度,高压氧组为186.5±27.3,对照组为246±41.6,差异有统计学意义(P＜0.05).胶原纤维面密度,高压氧组为(31.42±5.36)％,对照组为(43.62±7.36)％,差异有统计学意义(P＜0.05).Ⅰ型和Ⅲ型胶原含量,高压氧组分别为(71.42±5.36)％和(28.58±5.36)％,对照组为(62.46±7.32)％和(37.54±7.32)％,差异有统计学意义(P＜0.05).Ⅰ型和Ⅲ型胶原比例,高压氧组为2.499,对照组为1.664,高压氧组比例更为接近正常皮肤Ⅰ型和Ⅲ型胶原约4∶1的比例.结论 高压氧可促进创面愈合,并对兔耳早期增生性瘢痕有较明显的抑制作用.     

18F标记脱氧葡萄糖-正电子发射扫描成像在小鼠重症急性胰腺炎早期诊断和疗效评价中的应用

目的 评价18F标记脱氧葡萄糖-正电子发射扫描成像(18 F-FDG-PET)在小鼠重症急性胰腺炎早期诊断和疗效评价中的应用价值.方法 采用连续7次腹内注射雨蛙素(每次间隔1 h)及脂多糖制作小鼠重症急性胰腺炎模型,57只雌性ICR小鼠随机分为硼替佐米(PS-341)治疗组(注射脂多糖前0.5h腹内注射0.5 mg/kg PS-341),模型对照组[注射脂多糖前0.5h腹内注射50％二甲基亚砜(DMSO)],空白对照组(生理盐水制模).首次注射雨蛙素后8h将小鼠处死,每组3只行PET胰腺扫描,8只取胰腺组织测髓过氧化物酶(MPO),另外8只光学显微镜下观察小鼠胰腺的病理形态.结果 正常对照组PET扫描时胰腺不显影,与模型对照组比较,治疗组小鼠胰腺18F-FDG的吸收率(5.27±0.35,3.48±0.49)、胰腺MPO活性(3.46±0.28、1.82±0.54)均显著降低,两者之间差异有统计学意义(P＜0.05);胰腺组织的病理学也得到明显改善,进一步验证了18FFDG-PET在重症急性胰腺炎诊断和疗效评价中的应用价值.结论 18 F-FDG-PET能够动态监测重症急性胰腺炎的发展和转归,评价治疗效果.     

中药熏治联合高压氧对肛肠病术后创面愈合的作用

目的:探讨中药熏治联合高压氧对肛肠病术后创面愈合的作用。方法:选取肛肠病手术患者90例,随机分为中药熏治联合高压氧治疗组、高压氧组和对照组各30例,对照组行常规治疗,高压氧组每天给予高压氧治疗1次,联合治疗组在高压氧组基础上给予中药熏治20 min,连续治疗15 d;观察并记录创面愈合时间、创面面积及水肿情况。结果:联合治疗组创面愈合时间为(13.80±3.22)d,明显小于对照组(17.08±4.34)d和高压氧组(16.17±4.61)d。与对照组、高压氧组比较,联合治疗组术后第10、15 d创面面积均显著减小(均P0.05);联合治疗组术后第4、7天创面水肿积分(0.46±0.83、0.13±0.52),也明显小于对照组(1.83±0.95、1.51±0.84)和高压氧组(1.27±1.08、0.74±0.91),差异具有统计学意义(均P0.05)。结论:中药熏治联合高压氧可促进肛肠病术后创面溃疡愈合,加快组织消肿。     

白细胞介素-15对小鼠胃癌的治疗作用

目的 建立小鼠胃癌模型,检测荷瘤状态对小鼠免疫细胞的影响,同时给予白细胞介素-15(IL-15)免疫基因治疗,以检测IL-15对胃癌的预防及治疗效果.方法 采用多因素联合攻击法诱导小鼠胃癌,同时采用IL-15表达质粒载体进行免疫基因治疗.20周后取胃标本行病理学检查,并取血及脾细胞检测T细胞亚群及CD4+ CD25+调节性T细胞(Treg).同时进行自然杀伤(NK)细胞的细胞毒性试验,通过统计学方法分析结果.结果 多因素联合攻击法诱导胃癌发生率为37.5％.诱癌组小鼠血清IL-15水平(9.20±2.92) ng/L明显降低(P＜0.05),且其脾NK细胞杀伤活性(216.91±117.80) U/L明显降低(P＜0.05).诱癌组小鼠外周血Treg水平(8.07±6.62)％明显升高(P＜0.05),而对照组小鼠脾细胞Treg水平(4.40±3.34)％明显降低(P＜0.05).各组小鼠之间外周血T细胞亚群变化差异无统计学意义(P＞0.05).诱癌组小鼠脾细胞CD3+T细胞水平(78.31±29.79)％明显升高(P＜0.05),而CD4+T细胞(19.98±5.77)％及CD8+T细胞水平(10.15±1.72)％明显降低(P＜0.05).结论 多因素联合攻击法为小鼠胃癌模型建立提供了良好的模型.小鼠荷瘤状态下免疫功能下降,通过IL-15免疫基因治疗可提高机免疫功能,起到抗肿瘤的效果.     

吉西他滨化疗对免疫健全小鼠Panc02胰腺癌的作用以及对免疫环境的影响

目的 建立免疫健全小鼠Panc02胰腺癌皮下种植瘤模型.利用该模型观察吉西他滨化疗对免疫健全小鼠胰腺癌的作用以及对全身及肿瘤局部免疫环境的影响.方法 利用C57BL/6J小鼠同源Panc02胰腺癌细胞建立皮下种植瘤模型.待肿瘤生长至75 ～ 100 mm3时,将荷瘤小鼠分为化疗组和对照组.化疗组利用吉西他滨50 mg/kg腹腔内注射化疗,每周2次,共4周.绘制肿瘤生长曲线,最终称量荷瘤小鼠体质量、肿瘤重量及脾脏重量.流式细胞计数检测外周血与肿瘤组织中10个免疫细胞群的变化.实时荧光定量反转录-聚合酶链反应检测荷瘤小鼠脾脏及肿瘤组织中7种细胞因子水平.免疫组织化学法及Western blot检测CD34及淋巴管内皮透明质酸受体-1(LYVE-1)蛋白表达,并计数肿瘤组织中微血管密度(MVD)及淋巴管密度(LVD).结果 化疗组肿瘤体积明显小于对照组,在各个时间点比较差异有统计学意义(P＜0.05).化疗组荷瘤小鼠体质量明显小于对照组[(21.00±1.88)g比(28.36±1.06)g,P＜0.01].化疗组终末肿瘤重量明显小于对照组[(641.67 ±289.92) mg比(1 492.00±462.73)mg,P＜0.01].化疗组与对照组脾脏重量比较差异无统计学意义(P＞0.05).化疗后外周血中CD11c+树突状细胞增多[(22.93±2.26)％比(16.53±2.68)％,P＜0.05],CD11b+ Gr-1+髓系来源抑制细胞(MDSC)减少[(3.00±0.10)％比(7.03±0.32)％,P＜0.01].化疗后肿瘤组织中CD3+T淋巴细胞[(10.70±1.21)％比(21.10±3.54)％,P＜0.01]及MDSC[(5.10 ±2.11)％比(10.50±0.72)％,P＜0.05]减少,而树突状细胞[(17.13±3.21)％比(10.43±1.60)％,P＜0.05]、CD19+B细胞[(17.13±2.68)％比(7.90±1.87)％,P＜0.01]、Gr-1+粒细胞[(79.50 ±5.86)％比(46.00±3.75)％,P＜0.01]、CD3+NK1.1+自然杀伤T细胞(NKT)[(9.77±1.56)％比(4.90±1.81)％,P＜0.05]增多.化疗后脾脏中白细胞介素-4 (IL-4)表达升高(P＜0.05),而肿瘤坏死因子-α(TNF-α,P＜0.05)及IL-2(P＜0.01)表达下降.化疗后肿瘤组织中IL-4及转化生长因子(TGF)-β表达升高(P＜0.05),而IL-6、干扰素(IFN)-γ、TNF-α及IL-2表达均下降(P＜0.05或P＜0.01).化疗后肿瘤组织中MDSC效应产物精氨酸酶-1(Arginase-1)明显下降(P＜0.05).化疗后肿瘤组织中MVD(18.47±2.61比30.40±3.92,P ＜0.05)及LVD(6.66±2.77比16.27±2.02,P＜0.01)均下降.结论 吉西他滨可以抑制小鼠Panc02胰腺癌生长以及肿瘤组织中淋巴管及血管的生成,但也诱导产生了肿瘤局部和全身的免疫抑制效应,以肿瘤局部免疫抑制作用尤为明显.化疗诱导产生的免疫抑制效应以及肿瘤血管生成减少导致的肿瘤组织中血药浓度下降,可能是影响胰腺癌疗效的重要原因,有望成为提高胰腺癌化疗效果的重要靶点.     

高压氧治疗腰椎间盘突出症不同时机的疗效观察

目的 探讨高压氧治疗腰椎间盘突出症不同时机的临床疗效.方法 100例腰椎间盘突出症急性期患者随机分为两组:治疗组(急性期即予高压氧结合常规治疗)、对照组(急性期后予高压氧结合常规治疗),对照组50例,治疗组50例,2个疗程后进行疗效评价.结果 对照组:治愈22例,显效16例,无效12例,有效率76％;治疗组:治愈34例,显效11例,无效5例,有效率90％.经统计学分析,治疗组优于对照组(P＜0.05);两组治疗前后JOA评分比较有显著差异(P＜0.01),治疗后两组比较,治疗组优于对照组(P＜0.01);治疗前两组神经传导速度无明显差异,治疗前后比较,差异明显(P＜0.01),治疗后治疗组与对照组比较有显著性差异(P＜0.01).结论 高压氧结合常规治疗对腰椎间盘突出症患者疗效理想,并且不同时机给予高压氧治疗对腰椎间盘突出症患者的病情改善也不相同,急性期即予高压氧治疗效果更明显.     

吗替麦考酚酯抑制小鼠TH17细胞的分化和增殖

目的 通过观察吗替麦考酚酯(MMF)对小鼠辅助性T淋巴细胞17(TH 17细胞)分化和增殖的影响,探讨MMF的免疫抑制作用及其机制.方法 采用随机数字表法将小鼠分为MMF组与对照组,每组8只.MMF组小鼠每天给予MMF 40 mg·kg-1·d-1灌胃,对照组小鼠每天给予等体积生理盐水灌胃.3周后取小鼠外周血和脾脏,采用流式细胞术检测小鼠外周血和脾细胞中TH17细胞和CD4+CD25+调节性T淋巴细胞(Treg细胞)的比例,并计算出TH 17细胞与Treg细胞的比值;采用酶联免疫吸附试验法分别检测两组小鼠血清中白细胞介素(IL)-17和IL-23的浓度.结果 MMF组外周血和脾细胞中TH17细胞比例分别为(1.95±0.08)％和(2.42±0.06)％,对照组分别为(3.19±0.07)％和(4.21±0.25)％,两组比较,差异均有统计学意义(P＜0.05).MMF组外周血和脾细胞中TH 17细胞与Treg细胞的比值均显著低于对照组(P＜0.05).MMF组小鼠血清IL-17水平明显低于对照组(P＜0.05),而血清IL-23水平高于对照组(P＜0.05).结论 MMF能够明显抑制小鼠体内TH17细胞的分化与增殖,降低TH 17细胞与Treg细胞的比值,减少IL-17的分泌,有利于诱导免疫耐受.     

Hyperbaric Oxygen Therapy Reduces Severity and Improves Survival in Severe Acute Pancreatitis

Severe acute pancreatitis is characterized by pancreatic necrosis, resulting in local and systemic inflammation. Hyperbaric oxygen (HBO) therapy modulates inflammation, but has not been extensively studied in pancreatitis. This study investigates the effects of HBO in a rat model of severe acute pancreatitis. Sixty-four rats were induced with severe pancreatitis using 4% sodium taurocholate and randomized to HBO treatment or control. HBO was commenced 6 h after induction (100% oxygen at 2.5 atmospheres for 90 min) and continued every 12 h for a maximum of eight treatment episodes. Surviving animals were killed at 7 days. Severity of pancreatitis was graded macroscopically and microscopically. Lung edema was calculated using wet and dry lung weights. Macroscopic and microscopic severity scores (mean ± SE) of HBO-treated animals with pancreatitis (8.3 ± 0.7; 9.6 ± 0.4) were lower than those of controls (10.5 ± 0.5; 11.1 ± 0.4) (p = 0.02 and p = 0.03, respectively). The HBO-treated group had reduced pancreatic necrosis compared to controls (40 ± 4% vs. 54 ± 4%; p = 0.003). There was no difference in pulmonary edema between the groups. Median survival in the HBO-treatment group was 51 h, compared to 26 h in controls. Day-7 survival was significantly improved in the HBO-treated animals compared to controls (40% vs. 27%; p = 0.04). HBO therapy reduces overall severity, decreases the extent of necrosis, and improves survival in severe acute pancreatitis.     

门静脉动脉化对扩大肝-胆切除术后肝脏储备功能的影响

目的 观察慢性、梗阻性黄疸小型猪肝-胆切除术联合限流性部分门静脉动脉化(PPVA)术后肝脏储备功能的动态变化.方法 利用梗阻性黄疸小型猪模型,模拟进行联合半肝切除的肝门部胆管癌扩大根治性手术.实验分组:无黄疸对照组(A组,n=4)、门静脉动脉化组(B组,n=4)及非门静脉动脉化组(C组,n=4).对照观察根治术中应用限流性PPVA在术后30 d内的吲哚菁绿15 min滞留率(ICG15),从而判断肝脏储备功能的动态变化.结果 术前B、C组高于A组[(0.66±0.07)%、(0.64±0.09)%比(0.09±0.01)%,P＜0.01],术后第1天B组低于C高于A组[(0.59±0.11)%比(0.82±0.09)%、(0.18±0.04)%,P＜0.05、P＜0.01],术后第7天B组高于A组低于C组[(0.34±0.09)比(0.17±0.04)%、(0.69±0.11)%,P均＜0.05].术后第30天B组低于C组、与A组差异无统计学意义[(0.12±0.03)%比(0.22±0.03)%、(0.09±0.003)%,P＜0.01、P＞0.05].B组术后第7天低于术前[(0.34±0.09)%比(0.66±0.07)%,P＜0.01].结论 限流性PPVA可促进慢性梗阻性黄疸小型猪肝-胆切除术后残肝储备功能的恢复.

Abstract：

Objective To investigate the change of hepatic functional reserve (HFR) after flowcontrolled partial portal vein arterialization (PPVA) in hepato-biliary resection (HBR) in miniature pigs with obstructive jaundice. Methods Eight miniature-pig models with chronic gradually obstructive jaundice were divided into 2 groups with 4 pigs each: PPVA group (group B,n =4), non-PPVA group (group C, n = 4), and another 4 pigs without chronic gradually obstructive jaundice served as control group ( group A, n = 4). Approaches of EHBR with or without PPVA were done, then the effects of flow-controlled PPVA on HFR of remnant liver were studied by detecting indocyanine-green retention at 15 min ( ICG15 ) in 30 days post-operation. Results ICG15 in groups B and C was significantly higher than in group A pre-operation[(0.66±0.07)%, (0.64±0.09)% vs (0.09±0.01)%,P＜0.01]. ICG15 in group B was significantly lower than that in group C, and higher than in group A at the first day post-operation[(0. 59 ±0.11)% vs (0.82±0.09)%, (0.59±0.11)% vs (0. 18±0.04)%,P＜0. 05,P＜0. 01]. ICG15 in group B was significantly lower than in group C, and higher than in group A at 7th day post-operation [(0. 34±0.09)% vs (0.69 ±0. 11)%, (0.34±0.09)% vs (0. 17 ±0.04)% ,both P＜0.05]. ICG15 in group B was significantly lower than in group C, but showed no significant difference from group A at 30th day post-operation[(0.12 ±0.03)% vs (0.22 ±0.03)%, (0.12 ±0.03)% vs (0.09 ± 0. 003)% ,P ＜0. 01 ,P ＞ 0. 05]. ICG15 in group B on the 7th day post-operation was significantly lower than that pre-operation[(0. 34 ± 0. 09 ) % vs (0. 66 ± 0. 07 ) %, P ＜ 0. 01]. Conclusion Flow-controlled PPVA in HBR is beneficial to recovery of HFR on miniature pigs with obstructive jaundice.     

不同手术径路治疗SiewertⅡ型食管胃结合部腺癌的疗效评价

目的 探讨不同手术径路治疗进展期SiewertⅡ型食管胃结合部腺癌(食管浸润≤3 cm)的优缺点及疗效。方法 对251例SiewertⅡ型食管胃结合部腺癌患者施行D2或D2+的全胃切除术,其中经腹部正中切口组（the transabdominal approach,TA组）128例,经左胸腹联合切口组(the left thoracoabdominal approach,LTA组)123例,对两组的手术时间、术中出血量、远段食管切除长度、上切缘癌残留率、平均淋巴结清扫数目、围术期并发症发生率、病死率以及术后3、5年总体生存率进行对比分析。结果 TA组和LTA组的术后3、5年总体生存率分别为62.5％、39.0％和54.9％、31.9％,两组相比差异均无统计学意义(P＞0.05)。LTA组的远段食管切除长度较TA组稍长(5.6±1.1) cm比（5.4±1.1）cm,但两组手术的切缘癌残留率为1.6％（LTA组）比3.1％（TA组）,差异均无统计学意义（均P＞0.05）。TA组手术平均淋巴结清扫数目(23.4±8.7)枚,与LTA组的(23.7±8.4)枚比较差异无统计学意义(P＞0.05)。TA组在手术时间(227±24)min、术中出血量(270±78) ml及围术期并发症发生率(13.3％)和病死率(1.6％)方面均明显优于LTA组[(261±32) min、（342±59）ml,26.8％和6.5％],差异均具有统计学意义（均P＜0.05）。结论 对SiewertⅡ型食管胃结合部腺癌（食管浸润≤3 cm）患者,经腹部正中切口行全胃切除术（D2或D2+淋巴结切除术）可达到良好的根治目的,且围术期并发症的发生率和病死率均较低。     

线粒体ATP敏感性钾通道阻断剂对在体大鼠肺缺血后处理的作用及其机制

目的 探讨缺血后处理(IPO)对大鼠在体肺缺血-再灌注损伤(I/R)的保护作用及线粒体ATP敏感性钾通道(mitoKATP)在缺血后处理效应中的作用.方法 将Wistar大鼠35只随机分为5组:假手术组(Sham组)、缺血再灌注损伤组(I/R组)、缺血后处理组(IPO组)、缺血再灌注损伤+5-羟基葵酸盐组(I/R+5-HD组)、缺血后处理+5-羟基葵酸盐组(IPO+5-HD组).观察各组肺组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、湿/干比值(W/D)以及病理形态学改变.结果 I/R组与Sham组比较MDA含量增加[(5.07±1.60)nmol/mg prot比(1.43±0.41)nmol/mgprot,P＜0.01],SOD活性减低[(12.38±2.24)U/mg prot比(45.51±5.42)U/mg prot,P＜0.01],W/D比值增高(5.45±0.82比3.05±0.47,P＜0.01),肺组织形态及超微结构明显受损;IPO+5-HD组与IPO组比较MDA含量增加[(3.74±0.71)nmol/mg prot比(2.60±0.43)nmol/mg prot,P＜0.01],SOD活性减低[(22.91±2.71)U/mg prot比(28.74±2.03)U/mg prot,P＜0.01],W/D比值增高(4.64±0.79比3.89±0.60,P＜0.01),肺组织形态及超微结构明显受损;IPO组与I/R组比较,肺组织MDA含量减少[(2.60±0.43)nmol/mg prot比(5.07±1.60)nmol/mg prot,P＜0.01],SOD活性增高[(28.74±2.03)U/mg prot比(12.38±2.24)U/mg prot,P＜0.01],W/D比值减低(3.89±0.60比5.45±0.82,P＜0.01),肺组织病理形态学改变轻于I/R组;I/R+5-HD组与I/R组比较,肺组织MDA含量[(5.14±1.30)mol/mg prot比(5.07±1.60)mol/mg prot,P＞0.05)、SOD活性[(11.65±1.82)U/mg prot比(12.38±2.24)U/mg prot,P＞0.05]、W/D比变化(5.54±0.61比5.45±0.82),差异无统计学意义(P＞0.05),肺组织病理形态学改变无明显差异.IPO+5-HD组的各项指标介于IPO组和I/R组之间.结论 缺血后处理能减轻大鼠在体肺缺血再灌注损伤,mitoKATP参与了肺缺血后处理效应.

Abstract：

Objective To investigate the protective effect of ischemic postconditioning (IPO) on lung ischemic reperfusion (L/R) in rats in vivo and the mechanism of mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker in the ischemic postconditioning. Methods Thirty five Wistar rats were randomly divided into 5 groups: sham group, I/R group, ischemic postconditioning (IPO) group, I/R +5-hydroxydecanoate (I/R + 5-HD) group, IPO + 5-HD group. The concentration of malondialdehyde (MDA) and activity of superoide dismutase (SOD) were determined in the lung homogenate, wet to dry weight ratio (W/D) was measured and pathological changes were also observed. Results The levels of MDA[(5.07±1.60) vs (1.43 ±0.41) nmol/mg prot,P＜0. 01]and W/D (5.45 ±0.82 vs 3.05 ±0. 47,P ＜0. 01 ) were increased significantly in I/R group as compared with sham group, while the activity of SOD[( 12. 38 ±2. 24) vs (45.51 ±5.42) U/mg prot,P ＜0. 01]was decreased, and the injury of lung tissues was significantly aggravated in IPO + 5-HD group as compared with IPO group[MDA: (3.74 ±0. 71 ) nmol/mg prot vs (2. 60 ± 0. 43 ) nmol/mg prot , P ＜ 0. 01]; W/D: 4. 64 ± 0. 79 vs 3. 89 ± 0. 60,P＜0.01; SOD:[(22.91 ±2.71) U/mg prot vs (28.74±2.03) U/mg prot,P＜0. 01]. The levels of MDA[(2.60±0.43) vs (5.07 ±1.60) nmol/mg prot,P＜0. 01]and W/D (3.89 ±0.60 vs 5.45 ±0. 82,P ＜0. 01 ) were decreased significantly in IPO group as compared with I/R group, the activity of SOD[(28.74±2.03) vs (12.38 ±2.24) U/mg prot,P＜0. 01]increased and lung tissue histological damage attenuated. The difference in MDA[(5.14 ± 1.30) vs (5.07 ± 1.60) nmol/mg prot, P ＞ 0. 05],W/D (5.54±0.61 vs5.45 ±0.82,P＞0.05) and SOD[(11.65 ±1.82) vs (12.38 ±2.24) U/mgprot,P ＞ 0. 05]levels had no statistical significance between I/R + 5-HD group and I/R group, and the injury of lung tissues had no significant difference too. Each index in IPO + 5-HD group was between IPO and I/R groups. Conclusion Ischemic postconditioning can attenuate the lung I/R injury, and mitoKATP plays a vital role in the protective procession of ischemic postconditioning on lung ischemic reperfusion.     

电刺激迷走神经对脓毒症大鼠凝血功能的影响

目的 观察电刺激迷走神经对脓毒症大鼠凝血功能的影响.方法 采用经左侧股静脉注射脂多糖(LPS,10mg/kg)复制脓毒症模型.将雄性SD大鼠96只随机分成4组:生理盐水组(SHAM组)、脓毒症组(LPS组)、迷走神经切断组(VGX组)、电刺激迷走神经组(VNS组).将左侧迷走神经远端与双铂电极连接,于模型制备成功即刻行电刺激(5 V,2 ms,1 Hz)20 min.于注射脂多糖前(0 h),注入后2、4、6 h各个时间点取6只动物,经腹主动脉取血查血浆凝血酶原时间(PT)、活化部分凝血酶原时间(aPTT)、血浆凝血酶时间(TT)、血浆纤维蛋白原(Fbg)和肿瘤坏死因子-α(TNF-α)水平.结果 在予以LPS 2 h后,LPS组(316.34±23.96)ng/L和VGX组(325.77±39.77)ng/L血浆TNF-α水平较VNS组(252.72±30.36)ng/L升高(P＜0.05);6 h时,LPS组(10.68±0.66)s和VGX组(10.72±0.57)s与VNS组(9.67±1.04)s比较PT时间延长(P＜0.05);2 h时,LPS组(23.4 ±0.5)s和VGX组(23.9±0.5)s与VNS组(18.4±1.1)s比较aPTT时间延长(P＜0.05);4 h时,LPS组(32.0±1.0)s和VGX组(32.7±0.8)s与VNS组(28.7±1.9)s比较,TT时间延长(P＜0.05);4 h时,LPS组(1.909±0.224)g/L和VGX组(1.822±0.329)g/L与VNS组(2.376±0.138)g/L比较,Flg浓度降低(P＜0.05).结论 电刺激迷走神经不仅可以有效地抑制脓毒症大鼠血浆TNF-α水平,抑制炎症反应,而且还可以改善脓毒症大鼠的凝血功能紊乱.     

羟乙基淀粉对重症急性胰腺炎大鼠肝脏水通道蛋白-1表达及肝脏损伤的影响

目的 研究羟乙基淀粉130/0.4(万汶)对重症急性胰腺炎大鼠肝脏水通道蛋白-1(AQP-1)表达及肝脏损伤的影响.方法 将雄性SD大鼠48只按完全随机法分为假手术组(sham operation group,Sham组)、重症急性胰腺炎组(severe acute pancreatitis,SAP组)、羟乙基淀粉治疗组(HES组),每组分6 h、24 h两个时间点,每个时间点8只.以5%牛磺脱氧胆酸钠逆行胰胆管注射建立SAP模型.各组于造模后6 h、24 h处死大鼠,检测血淀粉酶(AMY),谷丙转氨酶(ALT),谷草转氨酶(AST),肝脏含水量,HE染色观察胰腺、肝脏组织病理,酶联免疫吸附(ELISA)方法检测血清TNF-α水平,RT-PCR检测肝组织AQP-1mRNA,免疫组化检测肝组织AQP-1蛋白.结果 各时间点SAP组与假手术组比较,血淀粉酶、ALT、AST、肝脏含水量、血清TNF-α水平、AQP-1mRNA及AQP-1蛋白均显著上调(P＜0.05);HES组与SAP组比较,血淀粉酶、ALT、AST、肝脏含水量、血清TNF-α水平、AQP-1mRNA及AQP-1蛋白均显著下调(P＜0.05).6 h时间点,Sham组、SAP组和HES组AQP-1mRNA表达量分别为(0.402±0.023)mmol/L、(0.811±0.032)mmol/L和(0.595±0.015)mmol/L,3组间差异有统计学意义(P＜0.05);24 h时间点,各组AQP-1mRNA表达量分别为(0.412±0.017)mmol/L、(0.823±0.029)mmol/L和(0.607±0.021)mmol/L,3组间差异有统计学意义(P＜0.05).6 h时间点,Sham组、SAP组和HES组AQP-1蛋白表达分别为(2.07±0.25)、(6.90±0.38)和(4.48±0.29),3组间差异有统计学意义(P＜0.05);24 h时间点,各组AQP-1蛋白表达分别为(2.32±0.31)、(7.04±0.32)和(4.56±0.25),3组间差异有统计学意义(P＜0.05).胰腺、肝脏组织病理HES组较SAP组明显改善.结论 HES130/0.4可一定程度改善重症急性胰腺炎的肝脏损伤,减轻毛细血管渗漏,AQP-1在重症急性胰腺炎肝脏损伤导致的毛细血管渗漏中起一定作用.

Abstract：

Objective To investigate the effect of hydroxyethyl starch (HES 130/0. 4) on the expression of aquaporin 1 (AQP-1) and liver injury in rats with severe acute pancreatitis(SAP).Methods Forty-eight male SD rats were randomly divided into three groups: Sham, SAP, and HES;each group was divided into 6 hour and 24 hour timepoints, with 8 in each subgroup. An SAP model was induced by injecting 5% sodium taurodeoxycholate into the biliary pancreatic duct. AMY, ALT,AST and water content in the liver were measured and TNF-a was examined by ELISA, and the expression of liver AQP-1mRNA was determined by RT-PCR, and the expression of liver AQP-Ⅰ protein was evaluated by immunohistochemical methods. Results Compared with the Sham group, the level of AMY, ALT, AST, TNF-a, water content, AQP-1mRNA and AQP-1 protein increased significantly in the SAP group (P＜0.05). Compared with the SAP group, the level of AMY, ALT, AST,TNF-a, water content, AQP-1mRNA and AQP-1 protein decreased significantly in the HES group (P＜0.05). At 6 hours, the expressions of liver AQP-1mRNA were (0. 402 ± 0. 023), (0. 811 ±0. 032) and (0. 595 ± 0. 015) in the Sham, SAP, and HES groups, respectively; at 24 hours, they were(0. 412 ± 0. 017), ( 0. 823 ± 0. 029) and (0. 607 ± 0. 021 ), with significant differences between each group (P＜0. 05). At 6 hours, the expressions of liver AQP-1 proteins were (2.07±0.25),(6.90±0.38)and (4.48±0.29) in the Sham, SAP and HES groups, respectively;at 24 hours, they were (2. 32±0. 31 ), (7. 04 ± 0. 32) and (4. 56 ± 0. 35), with significant differences between each group (P＜0. 05). Compared with the SAP group, the pathology of the pancreas and liver ameliorated significantly in the HES group. Conclusions Hydroxyethyl starch 130/0.4 may ameliorate liver injury of severe acute pancreatitis and alleviate the capillary leak. AQP-1 may play a role in the capillary leak caused by the liver injury of severe acute pancreatitis.     

骨髓间充质细胞和单个核细胞移植对糖尿病小鼠胰岛功能的影响

目的 比较骨髓间充质细胞移植和单个核细胞移植对糖尿病小鼠胰岛功能影响的差异.方法 建立糖尿病小鼠模型并分成3组:对照组(n=14)通过尾静脉注射磷酸盐缓冲液(PBS);单个核细胞组(n=14)通过尾静脉移植骨髓单个核细胞;间充质细胞组(n=14)通过尾静脉移植骨髓间充质细胞.观察移植后1周(n=6)和移植后6周(n=8),各组小鼠血糖的变化、胰岛数量、胰腺组织形态学特征及相关标记物的表达.结果 移植后1周,间充质细胞组小鼠血糖出现显著下降(16.6±1.6)mmol/L,与对照组(26.3±0.5)mmol/L和单个核细胞移植组(24.4±1.3)mmol/L比较差异有统计学意义(P＜0.05),并一直维持到移植后第6周,血糖下降到(16.5±1.5)mmol/L,与对照组(27.7±0.1)mmol/L比较差异有统计学意义(P＜0.05);移植后1周,间充质细胞组小鼠胰岛数目(21.2±1. 1)和胰岛β细胞数目(415.9±25.4)显著增加,与对照组(11.2±1.3)/(65.9±7.1)和单个核细胞组(12.2±1.3)/(64.1±6.5)比较差异均有统计学意义(P均＜0.05).单个核细胞组和间充质细胞组小鼠胰岛中均发现BrdU(+)Insulin(+)细胞和BrdU(+)Insulin(-)细胞.结论 骨髓间充质细胞移植改善糖尿病小鼠胰岛功能的效果优于骨髓单个核细胞移植.移植后胰岛的再生既来源于胰岛β细胞的增殖,也可能来源于胰岛干细胞的分化.

Abstract：

Objective To compare the different effects of bone marrow mononuclear cells vs mesenchymal cells transplantation on islets function of diabetic mice. Methods Mouse diabetic models were created by multiply peritoneal injection of low-dose streptozotocin (STZ) and divided into three groups:control group ( n = 14) , bone marrow mononuclear cells group ( n = 14) , and bone marrow mesenchymal cells group (n = 14). Blood glucose was measured weekly after transplantation by glucometer. Histochem istry and immunofluorescence were performed to characterize pancreatic histology, morphology and markers expressed in receipt pancreas. Results Compared with control group and bone marrow mesenchymal cells group, blood glucose levels in bone marrow mesenchymal cells group were significantly reduced at first week after transplantation[( 16. 6 ± 1.6 ) vs ( 26. 3 ± 0. 5 ) / ( 24. 4 ± 1.3 ) mmol/L, P ＜ 0. 05]and sustained to reduce at 6th week after transplantation[( 16. 5 ± 1.5 ) vs ( 27.7 ± 0. 1 ) mmol/L in control group,P＜0. 05]. One week after transplantation, the islets number in bone marrow mesenchymal cells group was larger than in control group ( 21.2 ± 1. 1vs 11.2 ± 1.3, P ＜ 0. 05 ) and bone marrow mononuclear cells group ( 21.2 ± 1. 1vs 12. 2 ± 1.3 ,P ＜0. 05 ). One weeks after transplantation, the beta cell number in bone marrow mesenchymal cells group was larger than in control group (415.9 ± 25.4 vs 65.9 ±7. 1,P＜0.05) and bone marrow mononuclear cells group (415.9 ±25.4 vs 64. 1 ±6.5,P＜0.05). In bone marrow mononuclear cells and bone marrow mesenchymal cells groups, there were several BrdU ( + )Insulin( - ) cells and BrdU( + )Insulin( - ) cells in the islets. Conclusion The effect of bone marrow mesenchymal cells transplantation to improve diabetic islet function is more satisfactory than bone marrow mononuclear cells transplantation. Bone marrow mesenchymal cells transplantation can initiate pancreatic islets β cells regeneration by both proliferation of β cells and differentiation of pancreatic stem cells.     

高压氧下调低氧诱导因子对急性胰腺炎的影响

目的 观察高压氧(HBO)抑制低氧诱导因子(HIF)活化对急性胰腺炎(AP)的影响.方法 40只Wistar大鼠随机分为假手术组、AP组、吸氧组和HBO组,每组10只.造模后4 h,吸氧组和HBO组大鼠分别接受常压下吸氧治疗和HBO治疗90 min;造模后6 h检测大鼠体内氧代谢水平;以免疫组织化学、激光共聚焦显微镜和Western blot法分析胰腺组织中HIF活化及血管内皮生长因子(VEGF)表达情况,检测胰腺组织髓过氧化物酶(MPO)含量和主要脏器干湿重比,以血清TNF-α和胰腺组织病理学评分评估病情.结果 免疫组织化学证实,AP组、吸氧组和HBO组腺泡细胞及中性粒细胞内HIF活化进入细胞核,并伴有VEGF高表达;与AP组[PaO_2:(86.6±5.6)nnn Hg(1 mm Hg=0.133 kPa);SaO_2:87.7%±1.8%]和吸氧组[PaO_2:(86.6±5.6)mm Hg;SaO_2:91.2%4±2.5%]比较,HBO组[PaO_2:(369.1±67.6)mm Hg;SaO_2:99.6%±0.7%]大鼠体内氧代谢水平升高(P<0,05);胰腺组织中HIF、VEGF和MPO含量减少,胰腺及胰外脏器水肿减轻,血清TNF-α和胰腺组织病理学评分降低(P<0.05).结论 HIF可促进AP炎症反应,HBO可以通过抑制HIF活化改善AP病情.     

白藜芦醇对急性胰腺炎肺损伤大鼠树突状细胞的影响

目的 观察白藜芦醇（resveratrol,Res）对重症急性胰腺炎（SAP）肺损伤大鼠树突状细胞（DC）的影响.方法 36只SD大鼠随机分为三组：假手术组、SAP模型组、Res治疗组（Res 10 mg/kg）,每组各12只.各组SD大鼠于制模后12 h处死,行胰腺及肺组织病理学检查和评分.提取肺树突状细胞,流式细胞仪检测DC表型CD80表达,并检测IL-12的分泌水平.结果 Res组肺和胰腺组织病理学评分分别为（3.49±1.02）和（6.43±1.40）,而SAP组分别为（6.12±2.02）和（11.00±2.58）,Res组评分均显著降低（P＜ 0.05）.SAP组DC细胞表面分子CD80阳性表达率为（45.3±6.7）％,而Res组为（20.1±3.2）％,显著低于SAP组,差异有统计学意义（P＜0.05）;Res组和SAP组DC分泌IL-12浓度分别为（1 676.5±121.8） g/L和（4 436.4±169.8） g/L,Res组IL-12浓度显著低于SAP组,差异有统计学意义（P＜0.05）.结论 Res能显著减轻SAP时肺和胰腺组织损伤,其机制与抑制肺DC活化有关.     

经皮穿刺置管引流与直接开腹手术引流治疗胰腺坏死组织感染的疗效比较

目的 比较经皮穿刺置管引流和直接开腹手术引流治疗重症急性胰腺炎(SAP)合并胰腺坏死组织感染的临床效果.方法 回顾性分析2008年1月至2009年12月治疗的90例合并胰腺坏死组织感染的SAP患者的临床资料,根据针对感染的胰腺坏死组织首先采取的治疗方法的不同将患者分为经皮穿刺置管引流组和直接开腹手术引流组,其中经皮穿刺置管引流组27例,直接开腹手术引流组63例.经皮穿刺置管引流组首先在彩色超声或CT引导下穿刺置管引流,冲洗3 d后评价引流效果,无明显改善则中转开腹手术引流.直接开腹手术引流组在确诊胰腺坏死组织感染后直接开腹手术引流.结果 经皮穿刺置管引流组的避免开腹手术引流率(48.1%比0,P＜0.05)和一次开腹手术引流成功率(92.9%比85.7%,P＜0.05)均明显高于直接开腹手术引流组,而术后残余脓肿(7.1%比28.6%,P＜0.05)、术后新发单脏器功能障碍(7.4%比28.6%,P＜0.05)、新发消化道瘘(7.4%比27.0%,P＜0.05)、远期并发症(3.7%比22.2%,P＜0.05)的发生率均低于直接开腹手术引流组.此外,经皮穿刺置管引流组的平均ICU治疗时间[(21.2±9.7)d比(28.7±12.1)d,P＜0.01],平均住院时间[(48.2±12.5)d比(59.6±17.5)d,P＜0.05]和住院费用[(191 762±5892)元比(341 689±10 854)元,P＜0.05]均低于直接开腹手术引流组.结论 经皮穿刺置管引流能有效降低多次开腹手术引流率和术后残余脓肿发生率,治疗后近期和远期并发症的发生率均明显下降,并且平均ICU治疗时间、平均住院时间、平均住院费用明显下降.