Role of Kupffer cells in acute hemorrhagic necrotizing pancreatitis-associated lung injury of rats

AIM:To investigate the role of Kupffer cells(KCs)inacute hemorrhagic necrotizing pancreatitis-associatedlung injury(AHNP-LI).METHODS:Forty-two rats were allocated to fourgroups[sham operation,AHNP model,gadoliniumchloride(GdCl_3)pretreatment,GdCl_3 control].In GdCl_3pretreatment group,GdCl_3 was administered by caudalvein injection 24 h before the AHNP model induction.Blood from the iliac artery,alveolar macrophages andtissues from the pancreas and lung,were collected insix animals per group 3 and 6 h after acute pancreatitisinduction.TNF-α,IL-1 of serum,myeloperoxidase(MPO)of lung tissue,NF-kB activation of alveolar macrophageswere detected.Serum AST and ALT in sham operationgroup and GdCl_3 control group were tested.In addition,histopathological changes of the pancreas and lung wereobserved under light microscope.RESULTS:MPO of lung tissue and TNF-α,IL-1 levelsof serum were all reduced significantly in GdCl_3pretreatment group compared to those in AHNP group(P<0.01).NF-kB activation of alveolar macrophageswas also attenuated significantly in GdCl_3 pretreatmentgroup compared to that in AHNP group(P<0.01).Thepathological injury of the lung was ameliorated obviouslyin GdCl_3 pretreatment group compared to that in AHNPgroup.Nevertheless,the serum amylase level did notreduce and injury of the pancreas was not prevented inGdCl_3 pretreatment group.CONCLUSION:Pulmonary injury induced by AHNPis mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCl_3 andKCs play a vital role in AHNP-LI.     

Calycosin attenuates severe acute pancreatitis-associated acute lung injury by curtailing high mobility group box 1 - induced inflammation

BACKGROUNDAcute lung injury (ALI) is a common and life-threatening complication of severe acute pancreatitis (SAP). There are currently limited effective treatment options for SAP and associated ALI. Calycosin (Cal), a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties, but its effect on SAP and associated ALI has yet to be determined. AIMTo identify the roles of Cal in SAP-ALI and the underlying mechanism.METHODSSAP was induced via two intraperitoneal injections of L-arg (4 g/kg) and Cal (25 or 50 mg/kg) were injected 1 h prior to the first L-arg challenge. Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically. An in vitro model of lipopolysaccharide (LPS)-induced ALI was established using A549 cells. Immunofluorescence analysis and western blot were evaluated in cells. Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1.RESULTSCal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI. Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP. Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, IL-1β, HMGB1 and chemokine (CXC motif) ligand 1 in lung tissue. Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B (NF-κB) p65 in lung tissues and an in vitro model of LPS-induced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI. Furthermore, molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1.CONCLUSIONCal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.     

急性胰腺炎大鼠肺组织中水通道蛋白-1的表达及功能

目的:研究水通道蛋白-1(AQP-1)在急性胰腺炎大鼠肺组织中的表达及其功能,探讨其表达与肺损伤的关系.方法:将Wistar大鼠分为假手术组(n=24)、肺损伤组(n=24)、地塞米松治疗组(n=24).采用逆行胰胆管注射15 g/L去氧胆酸诱发大鼠急性胰腺炎肺损伤模型,地塞米松组于造模后立即于尾静脉注射地塞米松2 mg/kg.每组分别于造模后4,8,12 h剖杀,取血及肺组织.通过检测血淀粉酶、血气、肺干/湿比值和肺组织病理切片判断胰腺炎及肺损伤的严重程度,放免法测血清TNF-α水平,RT-PCR检测肺组织AQP-1 mRNA的表达,免疫组化法检测肺组织AQP-1的表达.结果:与假手术组相比,胰腺炎肺损伤组血清淀粉酶、肺干/湿比值、TNF-α、肺组织病理损害程度明显升高,血氧、AQP-1mRNA(4 h:0.403±0.018 vs 0.794±0.015,P＜0.01;8 h:0.382±0.025 vs 0.812±0.032,P＜0.01;12 h:0.361±0.016 vs 198±5,P＜0.01)和AQP-1蛋白(4 h:104±4 vs 193±8,P＜0.01;8 h:96±5 vs 201±7,P＜0.01;12 h:94±3 vs198±5,P＜0.01)表达显著下调.与肺损伤组相比,地塞米松组血清淀粉酶、TNF-α、肺干/湿比值、肺组织病理损害程度明显降低,血氧、AQP-1 mRNA(4 h:0.681±0.031 vs 0.403±0.018,P＜0.05;8 h:0.763±0.013 vs 0.382±0.025,P＜0.05;12 h:0.784±0.032 vs 0.361±0.016,P＜0.05)和AQP-1的蛋白(4 h:145±6 vs104±4,P＜0.05;8 h:152±8 vs 96±5,P＜0.05;12 h:154±4 vs 94±3,P＜0.05)表达则明显升高,且与TNF-α的水平呈负相关性.结论:水通道蛋白-1表达与急性胰腺炎的肺损伤密切相关,其表达可能与TNF-α有关,地塞米松可上调其表达而减轻肺水肿.     

清胰汤对大鼠急性胰腺炎肺损伤时SP-A表达的影响

目的:探讨重症急性胰腺炎(SAP)肺损伤(ALI)时肺表面活性蛋白A(SP-A)的表达及其在ALI发病中的作用,并观察清胰汤对SP-A表达和病情转归的影响.方法:采用胆胰管内逆行注入1.5%去氧胆酸钠建立大鼠SAP时ALI模型.将SD大鼠随机分为假手术组(n=10)、模型组(n=10)和清胰汤组(n=10).假手术组仅行剖腹术,翻动胰腺.清胰汤组在建立SAP模型后30 min和12 h清胰汤ig(10 mL/kg).各组大鼠在术后24 h测PaO_2和血淀粉酶.应用逆转录聚合酶链式反应(RT- PCR)检测肺SP-A mRNA的表达强度,Western- blot观察SP-A表达,并观察胰、肺病理变化及肺泡Ⅱ型上皮细胞的电镜下变化.结果:模型组血淀粉酶(7144.19 U/L±727.91 U/L)显著高于清胰汤组(4283.51 U/L±527.52 U/L)和假手术组(1193.41 U/L±192.54 U/L,P<0.01).模型组PaO_2显著低于假手术组和清胰汤组(79.24±5.84 vs 96.78±3.81.79.24±5.84 vs 88.16±5.07,P<0.01).清胰汤组肺SP-A mRNA表达显著高于模型组(P<0.01),肺SP-A蛋白的表达显著高于模型组,SP-A mRNA的表达与肺损伤的程度呈负相关.清胰汤组胰、肺病理及电镜改变较模型组减轻.结论:SAP时肺泡Ⅱ型上皮细胞功能受损,SP-A mRNA表达降低导致急性肺损伤的机制之一.清胰汤能保护肺泡Ⅱ型上皮细胞功能,恢复SP-A mRNA正常表达,维持肺泡功能,从而对肺组织起保护作用.     

Establishment of the critical period of severe acute pancreatitis-associated lung injury

BACKGROUND:Since respiratory dysfunction is the main cause of death in patients with severe acute pancreatitis (SAP),elucidating the critical period of acute pancreatitis-associated lung injury(APALI)is of important clinical value. This study aimed to define the risk period of APALI by a series of studies including a dynamic analysis of total water content,ultrastructure and number of typeⅡalveolar epithelial cells,and reactive oxygen metabolites(ROMs)of lung tissue in a mouse model of SAP,and a clinical an...     

Role of fibronectin in pancreatitis-associated lung injury

Acute pancreatitis (AP) in humans can lead to increased vascular permeability in the lungs and respiratory failure. Fibronectin plays an important role in maintaining the structural integrity of the pulmonary epithelium and endothelium. However, its importance in pancreatitis-associated lung injury has not been defined. AP was produced by infusing caerulein (5 ug/kg/hr) in rats for 8 or 24 hr. Lung injury was assessed histologically and by determining lung microvascular permeability by bronchoalveolar lavage (BAL) analysis. Organ distribution of a target particle given intravenously was determined by the vascular clearance of magnetic iron oxide particles. Plasma fibronectin was measured by the enzyme-linked immunosorbent assay technique. After 8 hr of cerulein infusion, serum amylase increased 8-fold. Pancreatitis correlated with lung injury. BAL at 8 hr showed a 90% increase (P < 0.05) in albumin levels. Histological analysis at 8 hr revealed an increased number of leukocytes within the lungs. By 8 hr, plasma fibronectin significantly decreased 25% (P < 0.05) and the pulmonary uptake of iron oxide increased 111% (P < 0.05). By 24 hr, these effects had nearly resolved. These results indicate that decreases in serum fibronectin and increases in pulmonary leukocyte margination during acute pancreatitis may compromise the integrity of the air–blood barrier and also increase the pulmonary uptake of circulating pathogenic materials, thus making lung injury more likely.     

The effects of neutrophil depletion on a completely noninvasive model of acute pancreatitis-associated lung injury

Summary Conclusion A completely noninvasive animal model of acute pancreatitis-associated lung injury was used to show that neutrophils, activated by pancreatitis, play a key role in mediating pancreatitis-associated lung injury. Background Significant pulmonary complications have been known to occur in over 50% of patients with severe acute pancreatitis. Recent studies using a variety of animal models of pancreatitis have suggested that neutrophil activation may play an important role in mediating lung injury. However, in these models, the interpretation of the results is complicated because surgical manipulations alone could have resulted in the activation of neutrophils. Methods Young female mice were fed a choline deficient ethionine (CDE) supplemented diet. The severity of pancreatitis was evaluated by measuring hyperamylasemia, acinar cell necrosis, and pancreatic myeloperoxidase activity. Lung injury was quantified by measuring lung microvascular permeability and lung myeloperoxidase activity. To evaluate the role of neutrophils in CDE diet-induced pancreatitis-associated lung injury, animals were pretreated with antineutrophil serum. Results Mice fed the CDE diet develop pancreatitis-associated lung injury. Pretreatment of mice with antineutrophil serum results in marked depletion of circulating neutrophils. Under these conditions, the severity of pancreatitis is reduced and lung injury is completely prevented.     

重症急性胰腺炎大鼠肺组织中LIF的表达变化及意义

目的:观察重症急性胰腺炎(SAP)大鼠白血病抑制因子(LIF)在肺组织中表达的时相变化, 探讨LIF在SAP病程及肺损伤中的意义．方法:36只♂SD大鼠随机分为正常对照组(N 组,n=6)、假手术组(Sham组,n=6)和重症急性胰腺炎组(SAP组,n=24)．采用胰管逆行灌注50 g/L牛磺胆酸钠的方法复制大鼠SAP模型．用RT-PCR法检测肺组织中LIF mRNA的表达水平,免疫组织化学方法检测NLIF在肺组织中的表达变化．结果:SAP组3 h后肺组织LIF mRNA的表达量明显高于对照组和假手术组(灰度值:1．018± 0．065 vs 1．451±0．067,1．322±0．072,P<0,05), 并且6,12,24 h持续升高(0．853±0．058,0．635 ±0．064,0．582±0．089)(P<0．01)．同样,SAP组 LIF蛋白表达在3和6 h后明显高于对照组和假手术(127．36±2．76,122．53±2．43 vs 159．46 ±2．78,156．35±3．12,P<0．05),并且12,24 h后也维持在很高的水平(109．37±2．87,102．42± 2．27)．结论:LIF作为促炎症因子参与了SAP肺组织的炎症反应．     

急性坏死性胰腺炎相关性腹水与胰外脏器损伤的关系

急性坏死性胰腺炎(ANP)是一个始于局部而累及全身的炎症性疾病。急性坏死性胰腺炎产生大量的胰腺炎相关性腹水(PAAF),其中的弹性蛋白酶和腹膜巨噬细胞产生多种毒性细胞因子,可经腹膜吸收入血,通过不同的分子机制参与急性坏死性胰腺炎胰外多脏器的损害。     

重症急性胰腺炎肺损伤内皮素的变化及丹参的治疗作用

目的:探讨重症急性胰膜炎(SAP)肺损伤时血清和肺组织内皮素(ET)变化及丹参的保护作用．方法:Wistar大鼠60只,随机分为假手术组(J 组)、模型组(F组)和丹参治疗组(D组)．50 g／L 牛磺胆酸钠胰胆管逆行注射方法制作SAP模型．D组大鼠分别在造模前1 d和造模后10 min ip丹参注射液(5 mL／kg)．各组在制模后24 h及 48 h测定血清ET-1水平及其在肺组织(光密度) 表达情况,同时观察肺系数变化及肺组织病理学改变．结果:与J组比较,F组24和48 h肺组织损伤明显加重,血清ET-1水平(F组:75．8±4．8,70．4± 4．8 ng／L;J组:32．0±6．9,30．3±4．8 ng／L)和肺系数显著增高(F组:0．62±0．06,0．73±0．07;J 组:0．41±0．08,0．41±0．07)(P<0．01),肺组织24 和48 h ET-1表达增高(F组:0．48±0．09,0.61± 0．10;J组:0．05±0．01,0．05±0．01)(P<0．01)．与 F组比较,D组24和48 h肺组织学损伤明显减轻,血清ET-1水平和肺系数明显下降(60．2± 7．3 ng／L,0．52±0．06,P<0．05;57．9±5．43 ng／L, 0．58±0．06,P<0．01),肺组织ET-1表达明显减少(0．23±0．10,0．36±0．09,P<0．01)．相关性分析显示,造模后24和48 h肺组织ET-1表达与肺系数密切相关(r=0．736,P<0．01;r=0．828, P<0．01)．结论:ET-1在SAP肺损伤中起着重要的作用, 丹参对SAP肺损伤具有保护作用．     

清胰汤对急性胰腺炎肺损伤治疗作用的实验研究

[目的]探讨清胰汤在重症急性胰腺炎（SAP）急性肺损伤（ALI）时对肺表面活性蛋白A（SP-A）表达及病情转归的影响。[方法]将SD大鼠随机分为3组，各10只。假手术（对照）组仅行剖腹术，模型组采用胆胰管内逆行注入1．5％去氧胆酸钠建立大鼠SAP时ALI模型，清胰汤治疗（治疗）组在建立SAP模型后30min、12h清胰汤（10ml／kg）灌胃。各组术后24h测动脉血pH、动脉氧分压（PaO2）、动脉二氧化碳分压（PaCO2）、血淀粉酶（AMY）、肺湿／干重（W／D）比值。应用RT-PCR检测肺sP-A mRNA的表达强度，并观察胰、肺病理变化。[结果]模型组AMY、W／D及PaCO2显著高于对照组和治疗组（均P〈0．01）。而模型组pH、PaO2显著低于其他2组（P〈0．05，〈0．01）。治疗组肺sP-A mRNA表达显著高于模型组（P〈0．01），其表达与肺损伤的程度呈负相关。治疗组胰、肺病理改变较模型组减轻。[结论]清胰汤能保护肺泡Ⅱ型上皮细胞功能，恢复SP-A mRNA正常表达，维持肺泡功能，从而对肺组织起保护作用。     

Therapeutic effects of caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis

AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）.
METHODS： Forty-two SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18）; SAP-ICE-i group （n = 18）. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion, in SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum 1L-1β was measured by EUSA. Intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated.
RESULTS： Serum IL-1β levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly （P 〈 0.01, vs HC）. in SAP- ICE-I group, those values were decreased significantly （P 〈 0.01, vs SAP-S）. intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group （P 〈 0.01, vs HC）. The expression of IL-lβ and IL-18 mRNA were decreased significantly in the SAP- ICE-I group （P 〈 0.01, vs SAP-S）, whereas Caspase-1 mRNA expression had no significant difference （P 〉 0.05）. The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly （P 〈 0.05 at 6 h, P 〈 0.01 at 12 h and 18 h, vs HC） and they were decreased significantly in the SAP-ICE-I group （P 〈 0.05, vs SAP-S）.Caspase-1 inhibitors ameliorated the severit     

早期高容量血液滤过持续时间对重症急性胰腺炎急性肺损伤影响研究

目的 研究早期高容量血液滤过(HVHF)持续时间对重症急性胰腺炎(SAP)急性肺损伤(ALI)的影响.方法 将2006年8月到2009年4月怀化市第三人民医院ICU收治的49例入院时合并ALI急性呼吸窘迫综合征(ARDS)并在72 h内接受HVHF治疗的SAP患者随机分为两组.在常规治疗的基础上分别接受血滤持续时间8 h(Ⅰ组)和72 h(Ⅱ组)治疗.比较两组患者的APACHEⅡ评分、氧合指数、ALI/ARDS的改善率(包括治愈率)、机械通气的例数及时间、急性期并发症、HVHF相关并发症、结局及医疗费用等.结果 ①氧合指数及APACHEⅡ评分:两组入院第3天和第14天均较入院当天有所改善(P＜0.05).但在人院第3天和第14天,两组患者差异无统计学意义.②ALI、ARDS的改善率(包括治愈率):两组入院第3天和第14天较入院当天升高(P＜0.05);但在入院第3天和第14天.两组患者差异无统计学意义.③两组患者急性期机械通气的例数及时间、急性期并发症(多器官功能障碍综合征、急性肾功能衰竭、腹腔室隔综合征、导管相关感染、低血压)差异无统计学意义,但医疗费用差异有统计学意义(P＜0.05).两组患者急性期均无死亡.结论 发病72 h内的SAP早期短时(8 h)持续性HVHF治疗能有效促进合并ALI/ARDS的SAP患者肺功能的恢复,并且节约医疗费用.     

趋化因子CXCL11及其受体CXCR3在重症急性胰腺炎相关肺损害中的作用

目的:制作大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)模型,检测不同时间点趋化因子CXCL11及其受体CXCR3在SAP肺组织中的动态变化,探讨他们在SAP肺功能损害过程中的作用.方法:48只SD大鼠,雌雄不限,随机分为2组:对照组(C组),SAP组(P组),每组24只.4%牛黄胆酸钠逆行胰胆管注射建立SAP大鼠模型,剂量为1mL/kg,C组打开腹腔后仅仅翻动胰腺组织数次.每组随机分为4个亚组,每个亚组6只.4个组分别在1、3、6、12h抽血、处死,留取组织标本.分别检测各不同时间点组的血清淀粉酶、肺湿干重比,胰腺组织、肺组织病理,免疫组织化学法检测肺CXCL11及CXCR3的表达,酶联免疫吸附试验(ELISA)检测血清中的CXCL11的水平.结果:P组各亚组血清淀粉酶值明显升高(P<0.01vsC组);肺湿干重比值:P组3、6、12h组较C组明显升高(P<0.05);胰腺组织、肺组织病理:3、6、12hP组肺组织损伤明显;免疫组织化学显示P组CXCL11与CXCR3蛋白表达较C组表达明显增强(P<0.05),ELISA显示:1、3、6、12hP组血清CXCL11蛋白较C组明显增高(P<0.01).结论:CXCL11/CXCR3可能参与大鼠SAP急性肺功能损害的发病过程.     

Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats

AIM： To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis （SAP） and associated lung injury of rats. METHODS： Male adult SD rats were randomly divided into SAP group, sham-operation group, and MG-132 treatment group. A model of SAP was established by injection of 5% sodium taurocholate into the biliary- pancreatic duct of rats. The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally （ip） 30 min before the induction of pancreatitis. The changes in serum amylase, myeloperoxidase （MPO） activity of pancreatic and pulmonary tissue were measured. The TNF-α level in pancreatic cytosolic fractions was assayed with an enzyme-linked immunosorbent assay （ELISA） kit. Meanwhile, the pathological changes in both pancreatic and pulmonary tissues were also observed. RESULTS： MG-132 significantly decreased serum amylase, pancreatic weight/body ratio, pancreatic TNF-α level, pancreatic and pulmonary MPO activity （P 〈 0.05）. Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema, cellular damage, and inflammatory activity （P 〈 0.05）. CONCLUSION： The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.     

Heliox attenuates lung inflammation and structural alterations in acute lung injury

Low-density gas mixtures, such as heliox, were shown to reduce the work of breathing and facilitate the distribution of inspired gas. Since supplemental ventilatory and oxygen requirements may lead to pulmonary inflammation and structural alterations, we hypothesized that by reducing these requirements, heliox breathing may attenuate the acute inflammatory and structural changes associated with acute lung injury. Spontaneously breathing neonatal pigs were anesthetized, instrumented, supported with continuous positive airway pressure (CPAP), injured with oleic acid, and randomized to nitrox (n = 6) or heliox (n = 5).F(I)O(2) was titrated for pulse oximetry (SpO(2)) 95 +/- 2% for 4 hr. Gas exchange and pulmonary mechanics were measured. Lungs were analyzed for myeloperoxidase (MPO), interleukin-8 (IL-8), and histomorphometery. Relationships between physiologic indices and cumulative lung structure and inflammatory indices were evaluated. With heliox, compliance was significantly greater, while tidal volume, frequency, minute ventilation, F(I)O(2), arterial carbon dioxide tension (PaCO(2)), MPO, and IL-8 were significantly lower compared to nitrox. The expansion index and number of exchange units were significantly greater with heliox, while the exchange unit area (EUA) was smaller. MPO was significantly and positively correlated with F(I)O(2) (r = 0.76) and EUA (r = 0.63), and negatively correlated with number of open exchange units/field (r = -0.73). Compared to breathing nitrox, these data indicate that heliox improved the distribution of inspired gas, thereby recruiting more gas exchange units, improving gas exchange efficiency, reducing ventilatory and oxygen requirements, and attenuating lung inflammation. These data suggest that heliox breathing may have the combined therapeutic benefits of attenuating lung inflammation by reducing mechanical and oxidative stress in the clinical management of acute lung injury.     

Effect of resveratrol on microcirculation disorder and lung injury following severe acute pancreatitis in rats

AIM: To investigate the mechanism of resveratrol underlying the microcirculation disorder and lung injury following severe acute pancreatitis (SAP). METHODS: Twenty-four rats were divided into 3 groups (SAP, sham and resveratrol groups) randomly. SAP model was established by injecting 4% sodium taurocholate l mL/kg through puncturing pancreatic ducts. Sham (control) group (8 rats) was established by turning over the duodenum. Resveratrol was given at 0.1 mg/kg b.m. intraperitoneally. Rats were sacrificed 9 h after SAP was induced. Blood samples were obtained for hemorrheological examination. Lung tissues were used for pathological observation, and examination of microvascular permeability, dry/wet ratio and myeloperoxidase (MPO) activity. Gene expression of intercellular adhesion molecule-1 (ICAM-1) was detected by RT-PCR. RESULTS: Compared with SAP group, resveratrol relieved the edema and infiltration of leukocytes in the lungs. Resveratrol improved markers of hemorrheology: high VTB (5.77±1.18 mPas vs9.49±1.34 mPas), low VTB (16.12±3.20 mPas vs30.91±7.28 mPas), PV (4.69±1.68 mPas vs 8.00±1.34 mPas), BSR (1.25±0.42 mm/h vs50.03±0.03 mm/h), VPC (54.67±3.08% vs 62.17±3.39%), fibrinogen (203.2?7.8 g/ L vs 51.3±19.1 g/L), original hemolysis (0.45±0.02 vs 0.49±0.02), and complete hemolysis (0.41±0.02 vs 0.43±0.02) (P<0.05). Resveratrol decreased the OD ratio of ICAM-1 gene (0.800±0.03 vs 1.188±0.10), dry/wet ratio (0.74±0.02 vs 0.77±0.03), microvascular permeability (0.079±0.006 vs 0.112±0.004) and MPO activity (4.42±0.32 vs 5.03±0.51) significantly (P<0.05). CONCLUSION: Resveratrol can improve the microcirculation disorder of the lung by decreasing leukocyte-endothelial interaction, reducing blood viscosity, improving the decrease of blood flow, and stabilizing erythrocytes in SAP rats. It may be a potential candidate to treat SAP and its severe complications (ALI).     

生长抑素类似物对大鼠急性胰腺炎PAP的影响

目的:观察生长抑素类似物(奥曲肽)对实验性急性胰腺炎(acute pancreatitis,AP)胰腺炎相关蛋白(pancreatitis-associated protein,PAP)的表达及胰腺组织病理变化的影响.方法:Wistar大鼠80只,随机分为阴性对照组、假手术组、手术组、治疗组,每组均在6,12h采集标本.胰腺组织病理切片证实后,对PAP进行半定量RT-PCR及免疫组化检测,其血清做ELISA检测.结果:免疫组化结果显示,手术组PAP表达比假手术组显著增强(x~2=26.11,P<0.01),治疗组比手术组显著降低(x~2=15.65,P<0.05).RT-PCR及ELISA显示,PAP在手术后组织和血清中的表达明显升高,经奥曲肽治疗后明显降低,3组间有显著差异(RT-PCR:F=71.3,P<0.01;ELISA:F=925,P<0.001).免疫组化、RT-PCR及ELISA结果组内比较显示,手术组PAP表达随时间逐渐显著升高,6,12h之间比较有显著差异(x~2=16.92,P<0.05;t= 2.49,P<0.05;t=2.56,P<0.05),而其他组(治疗组ELISA结果除外)6,12h之间无显著差异(P>0.05).手术组病理改变明显.结论:PAP是AP早期表达明显升高的蛋白,对奥曲肽反应敏感,对胰腺炎的诊断和预后判断有一定作用.     

褪黑素对急性胰腺炎相关性肺损伤中趋化因子MIP-2表达的影响

目的观察褪黑素(MT)对ANP大鼠肺组织趋化因子巨噬细胞炎性蛋白-2(MIP-2)表达的影响,探讨MIP-2在ANP相关肺损伤发病机制中的作用。方法35只SD大鼠随机分为假手术组(SO组),ANP 3h、6h、12h组和MT 3h、6h、12h组,每组5只。采用4%牛磺胆酸钠胰胆管逆行注射制备ANP动物模型,MT组在ANP诱导前30min腹腔注射MT 20mg/kg体重。检测血淀粉酶,观察肺组织病理学改变,采用实时定量RT-PCR法和免疫组化检测肺组织中MIP-2 mRNA和蛋白的表达。结果与SO组相比,ANP 3h、6h和12h组肺组织MIP-2 mRNA表达分别增加48%,137%和230%。ANP组MIP-2蛋白表达量分别为3.40±0.84,5.80±0.55和6.40±0.45。MT干预组肺组织损伤得到改善,MIP-2 mRNA表达分别为ANP相应时间点的87%,77%和84%,MIP-2蛋白表达分别为2.20±0.84.4.20±0.45和5.20±0.50,与ANP相应时间点比较,相差显著(P<0.05)。结论MIP-2在ANP相关肺损伤发病中起一定作用,MT可能通过下调MIP-2的表达以减轻ANP相关肺损伤的程度。