单核细胞趋化蛋白-1激活在急性重症胰腺炎发病中的作用

目的：探讨单核细胞趋化蛋白1激活在急性重症胰腺炎发病机制中的作用。方法：急性胰腺炎患者86例中急性重症胰腺炎41例，检测外周血中单核细胞趋化蛋白-1激活。结果：急性胰腺炎患者单核细胞趋化蛋白-1激活在发病后均有所升高，但是轻症胰腺炎患者升高幅度较重症胰腺炎患者明显减少，轻症胰腺炎患者在1周后单核细胞趋化蛋白-1已经降低到接近正常，而重症组患者在第10d时检测发现开始出现降低，在2周时仍然处于高位状态。结论：急性胰腺炎患者早期外周血单核细胞趋化蛋白-1明显激活，单核细胞趋化蛋白-1激活在急性胰腺炎发展中起重要作用。     

Role of immunological disorders in the pathophysiology of severe acute pancreatitis

Severe acute pancreatitis is a disease associated with high mortality, causes of which are multiple organ failure(MOF) in the early course and the development of bacterial infections in the later course. Inflammatory response leading to organ failure continues to be one of the major problem after acute pancreatitis. This review summarizes recent studies that demonstrate the critical role played by inflammatory mediators in acute pancreatitis. Immunological disorder, immune suppression, also plays a role at high risk of sepsis in the development of severe acute pancreatitis. We have to clarify the mechanism of immunological suppression in the development of bacterial infections in severe acute pancreatitis. It is important that the elucidation of key mediators in MOF and the mechanism of immune suppression in the development of bacterial infection could be improved by the prognosis of severe acute pancreatitis.     

Role of free radicals in the development of severe acute pancreatitis

Acute pancreatitis is an inflammatory disease which leads to acinar cell damage, interstitial edema, and hemorrhage. Some patients develop severe acute pancreatitis and result in multiple organ dysfunction syndrome. Acute pancreatitis is initiated by the activation of pancreatic enzyme in acinar cells. Following activation of trypsinogen into trypsin, local inflammation is initiated and activated inflammatory mediators are produced. Polymorphonuclear neutrophils, macrophages, and lymphocytes release lysosomal enzymes, oxygen free radicals, vasoactive substances, and proinflammatory mediators. In the course of the development of acute pancreatitis oxygen-free radicals and their derivatives play an important role as the molecular trigger in constituting lesions in the pancreas. Damaged acinar cells as well as activated neutrophils and macrophages produce large amount of oxygen radicals in acute pancreatitis. The hydrogen peroxide, superoxide, the hydroxyl radical, and singlet oxygen are key elements capable of cellular injury in acute pancreatitis. These highly reactive species cause various reactions, such as destruction of lipid membranes by peroxidation of fatty acids and destruction of lysosomal membranes. The oxygen radicals generated in the circulation might injure the capillary endothelium, and play an important role in accelerating the progression of acute pancreatitis. The imbalance of oxygen radical generating and oxygen radical scavenging processes is considered to lead to the cell injury in acute pancreatitis. These oxygen radicals are not only restricted in the pancreatic tissue, but involved in the systemic manifestation of the disease, particularly in the lungs, liver, and blood.     

氧化应激及凋亡与重症急性胰腺炎肠屏障功能障碍

目的 通过动物实验,观察重症急性胰腺炎(severe acute pancreatitis,SAP)肠道屏障功能变化,探讨炎症因子释放、肠黏膜氧化应激及凋亡在肠屏障功能障碍中的作用.方法 上海交通大学附属第一人民医院动物实验中心内,24只BALB/c小鼠,随机数字法分为2组,SAP组:以雨蛙素联合脂多糖腹腔注射法诱导,先腹腔内注射雨蛙素50 μg/kg,连续6次,每次间隔1h,在末次雨蛙素注射同时,腹腔内注射脂多糖10 mg/kg(LPS E.Coli);对照(假手术)组:每小时一次腹腔注射生理盐水2 ml,共6次.两组动物分2批(每批6只/组)分别于建模后4h及8h,麻醉后打开腹腔取血及标本.观察小鼠胰腺及肠道病理变化并予评分,测定小鼠血二胺氧化酶(diamine oxidase,DAO)、淀粉酶、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量,测定肠黏膜丙二醛( malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、还原型谷胱甘肽( glutathione,GSH)含量及黄嘌呤氧化酶(xanthine oxidase,XO)活力,检测小鼠肠黏膜细胞caspase-3酶活性,脱氧核糖核苷酸末端转移酶介导的缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)法检测小鼠肠黏膜凋亡细胞并计算凋亡指数.以PASW 18.0软件对数据进行方差分析及t检验,明确上述检测指标在两组小鼠间差异是否有统计学意义,从而明确重症急性胰腺炎肠道屏障功能障碍的机制.结果 建模后4h及8h,SAP组小鼠胰腺出血、坏死、炎症细胞浸润较对照组严重,胰腺病理评分与对照组比较差异具有统计学意义(P＜0.01),血淀粉酶含量与对照组比较差异具有统计学意义(P＜0.05);肠组织病理评分及血DAO质量浓度与对照组比较差异具有统计学意义(P＜0.01);血TNF-α质量浓度与对照组比较差异具有统计学意义(P＜0.01);肠黏膜MDA含量及XO活力与对照组比较差异具有统计学意义(P＜0.01),肠黏膜SOD含量与对照组比较差异具有统计学意义(P＜0.01)、GSH含量与对照组比较差异具有统计学意义(P＜0.05);肠黏膜细胞caspase-3酶活性及凋亡指数与对照组比较差异具有统计学意义(P＜0.01).结论 重症急性胰腺炎发病后,TNF-α等炎症因子瀑布样释放,导致肠黏膜缺血-再灌注损伤,形成严重的氧化应激反应,进一步激活caspase-3通路,导致肠黏膜细胞凋亡增加,是肠黏膜屏障功能受损的重要机制.     

细胞外调节蛋白激酶与核因子-κB活化对重症急性胰腺炎大鼠中性粒细胞凋亡延迟的调控作用

目的探讨细胞外调节蛋白激酶和核因子-κB活化对重症急性胰腺炎（severe acute pancreatitis,SAP）大鼠中性粒细胞凋亡延迟的调控作用。方法60只雄性SD大鼠随机分为对照组、SAP组、吡咯烷二硫代氨基甲酸盐（pyrrolidine thiocarbamate,PDTC）组（CPTC组）和细胞外调节蛋白激酶特异性抑制剂PD98059组各15只,对照组大鼠仅作开腹再缝合,SAP组、PDTC组和PD98059组大鼠采用胆胰管逆行注射质量分数4％牛磺胆酸钠建立SAP模型,PDTC组和PD98059组大鼠造模前分别注射PDTC和PD98059,对照组和SAP组仅注射等量生理盐水。24h后于大鼠下腔静脉取血分离中性粒细胞,体外培养16h后采用流式细胞仪检测中性粒细胞凋亡率和Bcl—xl基因表达情况。结果体外培养16h后,SAP组中性粒细胞凋亡率明显低于对照组、PDTC组和PD98059组（P〈0．01）,Bcl—xl基因表达水平明显高于对照组、PDTc组和PD98059组（P〈0．01）;PDTC组和PD98059组中性粒细胞凋亡率低于对照组（P〈0．01）;PD98059组Bcl—xl基因表达水平高于对照组（P〈0．01）,PDTC组与对照组比较差异无统计学意义（P〉0．05）。结论SAP时大鼠中性粒细胞中Bcl-xl表达明显增加,导致其自发凋亡率减低,PD98059或PDTC可明显抑制Bcl-xl表达,恢复其自发凋亡率。     

Aprotinin in severe acute pancreatitis

Aprotinin, a Kunitz protease inhibitor, has a wide inhibitory action with particular activity against trypsin, chymotrypsin and kallikrein, making it theoretically attractive in ameliorating the effects of acute pancreatitis. Its use in acute pancreatitis has been studied for the last 50 years with disappointing results. In this paper, we review the previous studies and argue that all the studies have not been adequately powered, have inappropriate end‐points, but most importantly have not attained adequate plasma and peritoneal levels of aprotinin to produce sufficient inhibitory activity. We hypothesise that a well‐powered study with adequate aprotinin dosing may clarify its clinical benefit in severe acute pancreatitis.     

生长抑素及生长激素对重症急性胰腺炎外周血中性粒细胞凋亡的干预作用

目的探讨外周血中性粒细胞凋亡在重症急性胰腺炎(SAP)发病机制中的作用,以及生长抑素(SS)和生长激素(GH)对外周血中性粒细胞凋亡水平的调节作用。方法采用流式细胞仪检测重症急性胰腺炎外周血中性粒细胞凋亡水平,以及SS、SS+GH序贯疗法对中性粒细胞凋亡的影响。结果SAP患者外周血中,中性粒细胞凋亡明显延缓。MODS患者的中性粒细胞凋亡延缓较SIRS患者显著。SS治疗能纠正中性粒细胞凋亡延缓(P<0.05)。SS+GH序贯疗法组与SS组比较差异无显著性(P=0.05)。结论中性粒细胞凋亡延缓是重症急性胰腺炎发病的重要机制,并与疾病的严重程度相关。生长抑素通过改善中性粒细胞凋亡,对重症急性胰腺炎有治疗作用,与生长激素联用,有协同作用。     

细胞凋亡在急性重症胰腺炎肠道粘膜屏障功能障碍中的意义

目的：探讨细胞在凋亡在大鼠急性重症胰腺炎（ＡＳＰ）肠道粘膜屏障功能障碍中的意义。方法：用胰胆管内注射甘脱氧胆酸,结合静脉输注蛙皮素方法复制大鼠ＡＳＰ模型。分别对模型大鼠（ＡＳＰ）及假手术组大鼠（ＳＯ）于术后６、１２、２４小时取回肠粘膜组织进行光镜、电镜观察,并用分子生物学标记（ＴＵＮＥＬ）方法定量肠粘膜上皮细胞的凋亡指数。结果：ＡＳＰ组大鼠除制模２４小时光镜下可见肠粘膜上皮脱落及溃疡形成外,其它两     

肥胖对急性胰腺炎作用的研究进展

胰腺是人体的重要器官,具有内外分泌功能,在全身代谢、消化吸收中发挥重要作用。近年来,随着肥胖人群的增加,肥胖相关性急性胰腺炎的发病率逐年上升,且重症化趋势明显,然而肥胖在急性胰腺炎发生发展中的作用机制尚未阐明。本文旨在对肥胖在急性胰腺炎中的作用作一综述,以期为急性胰腺炎发病机制的理解和新治疗靶点的提出提供参考。     

重症急性胰腺炎的治疗现状

重症急性胰腺炎(SAP)是常见急腹症及危重症之一,它不仅是胰腺的局部炎症病变,而且是涉及多个脏器的全身性疾病,发病急、变化快、并发症多、病死率极高。随着现代监护、诊疗手段的不断发展及对SAP病理生理过程研究的深入,其治疗方针发展为现阶段个体化治疗方针[1]。本文现介绍近年来SAP的治疗现状,综述如下。     

手术治疗重症急性胰腺炎

目的:探讨重症急性胰腺炎的手术时机与方式,以降低病死率。方法:1990～2002年收治86例重症急性胰腺炎患者均在ICU行监护及支持治疗,对其一般状况、疾病诊断、手术经过、治疗方法和疗效进行回顾研究。结果:胰腺感染局限或脓肿形成者的手术次数及手术死亡率明显低于有感染性胰腺坏死或液体积聚立即手术者。结论:胰腺感染局限或胰腺脓肿形成时,手术治疗效果好。     

腹腔巨噬细胞在重症急性胰腺炎大鼠肠屏障功能损害中作用

目的探讨清除腹腔巨噬细胞（peritoneal macrophages,PMs）对重症急性胰腺炎（severe acute pancreatitis,SAP）大鼠肠道屏障功能的影响。方法36只SD大鼠随机分为PMs保留组、PMs清除组和假手术组,每组12只。PMs保留组与PMs清除组经胆胰管逆行注射质量分数2％去氧胆酸钠建立大鼠SAP模型,假手术组注射生理盐水。PMs清除组分别于造模前5d、前2d腹腔注射氯屈磷酸二钠脂质体清除PMs,PMs保留组与假手术组同样时间注射等量空脂质体。检测3组血清淀粉酶及血浆D-乳酸水平,比较胰腺病理评分、肠道转运系数及脏器细菌移位率。结果PMs保留组与PMs清除组血清淀粉酶水平（（9399±923）、（9012±852）u／L）高于假手术组（（1367±360）u／L）（P〈0．01）,PMs保留组与PMs清除组比较差异无统计学意义（P〉0．05）;假手术组大鼠肠道转运系数（0．46±0．12）高于PMs清除组（0．33±0．10）与PMs保留组（0．23±0．09）（P〈O．01）,PMs清除组高于PMs保留组（P〈0．05）;假手术组大鼠脏器细菌移位率（（5．60±0．68）％）、血浆n乳酸水平（（5．66±0．43）mg／L）低于PMs清除组（40．55±5．67）％,（8．96±0．67）mg／L）与PMs保留组（（51．63±7．53）％,（12．62±0．89）mg／L））（P〈0．01）,PMs清除组低于PMs保留组（P〈0．05）;PMs清除组胰腺病理评分（7．9±1．2）与PMs保留组（7．6±0．9）比较差异无统计学意义（P〉0．05）。结论造模前PMs消耗对SAP大鼠肠道屏障功能有保护作用。