表皮生长因子对雨蛙肽联合应激诱导的大鼠急性出血性胰腺炎的保护作用

表皮生长因子(EGF)是参与细胞增殖、成熟和再生的主要因子。目前已证实其对胃肠道黏膜具有保护作用,能促进溃疡愈合,但是罕见关于EGF在急性出血性胰腺炎中作用的报道。目的:观察外源性EGF对雨蛙肽联合应激诱导的大鼠急性出血性胰腺炎的保护作用。方法:予雄性Sprague鄄Dawley大鼠腹腔内注射雨蛙肽(40μg/kg,两次注射间隔1h)联合水浸束缚应激(第一次注射雨蛙肽后开始,持续5h)诱导急性出血性胰腺炎。EGF治疗组第一次注射雨蛙肽之前0.5h和之后2.5h,分别皮下注射EGF1、10或30μg/kg。观察各组动物胰腺炎生化、病理学等指标的变化。结果:制模开始后12h,对照组的胰腺湿重为4.24g/kg±0.68g/kg,血清淀粉酶含量为4325U/L±822U/L,胰腺组织DNA和淀粉酶含量分别为1577μg/g±433μg/g和21.39U/mg蛋白±6.83U/mg蛋白,各病理学指标评分均为0。胰腺炎组的胰腺湿重(10.49g/kg±1.87g/kg)和血清淀粉酶含量(24433U/L±16751U/L)较对照组显著增高(P<0.01),胰腺组织DNA(561μg/g±278μg/g)和淀粉酶含量(16.95U/mg蛋白±5.01U/mg蛋白)则降低,病理学评分显著增高(P<0.01)。10μg/kgEGF能显著降低胰腺湿重(6.47g/kg±2.64g/kg,P<0.01)和血清淀粉酶含量(9010U/L±3983U/L,P<0.05),提高胰腺组织淀粉酶含量(23.92U/mg蛋白±8.58U     

人重组血管生成素-1对小鼠急性胰腺炎的治疗作用及机制

目的观察血管生成素-1(Ang-1)对小鼠急性胰腺炎(AP)的治疗作用,并探讨其作用机制。方法BALB/c小鼠54只,随机分为对照组、AP组、Ang-1治疗组(各18只)。AP组:腹腔注射雨蛙素50μg/kg,1次/h,共7次,制成AP模型;Ang-1治疗组:同法制作AP模型,之后腹腔注射100μg/kg的Ang-1;对照组:腹腔注射等量生理盐水。上述各组小鼠在作相应处理后分别于9、18、24 h各取6只,摘眼球取血处死,取胰腺组织观察其病理变化并评分(Schmidt法),检测小鼠血清淀粉酶(AMY)、TNF-α、IL-6。结果 AP组胰腺组织病理学评分及血清AMY、TNF-α、IL-6水平较对照组明显升高(P均<0.01),Ang-1治疗组胰腺组织病理学评分及血清AMY、TNF-α、IL-6水平较AP组下降(P均<0.05)。结论 Ang-1可明显减轻雨蛙素诱导的小鼠AP的炎症反应及胰腺损伤,其作用机制与降低炎症因子TNF-α、IL-6的水平有关。     

急性胰腺炎小鼠对脂多糖耐受性及其机制的研究

目的　观察急性胰腺炎(AP)小鼠对脂多糖(LPS)的耐受性并探讨其可能机制。方法　210只C57BL/6J小鼠分为生理盐水(NS)+LPS组(n=105)和AP+LPS组(n=105),两组均以不同LPS剂量分为7个亚组。AP模型制备采用间隔1 h腹腔内注射雨蛙肽(50μg/kg),共7次,于第1次雨蛙肽注射后6 h腹腔内注射LPS;NS+LPS组以NS代替雨蛙肽。每个亚组随机分出10 只观察7 d死亡率,其余5只于第1 次雨蛙肽注射后12 h处死,留取血清及肝、肺、肾、胰腺等组织,检测血清淀粉酶(AMS)、乳酸脱氢酶(LDH)水平及各脏器病理学改变。应用含12 489条小鼠全长基因的寡核苷酸芯片分别检测NS+LPS(15 mg/kg)亚组和AP+ LPS(15 mg/kg)亚组小鼠血白细胞基因表达谱并重复3次,筛选两组间的表达差异基因。结果　NS+LPS组和AP+LPS组死亡率均随LPS剂量增加逐步升高,AP+LPS组死亡率均显著低于同等LPS剂量的NS+LPS组(P<0.05)。AP+LPS组LDH水平明显低于相同LPS剂量的NS+LPS组(P<0.05),而AMS水平显著高于相同LPS剂量的NS+LPS组(P<0.05)。AP+LPS组肝、肺、肾组织损伤较相同LPS剂量的NS+LPS组明显减轻。基因芯片筛选结果显示,AP+LPS(15 mg/kg)亚组与NS +LPS(15 mg/kg)亚组相比炎症反应基因、细胞内信号传导基因、转录调节基因表达下调。结论　AP可增强小鼠对LPS耐受性,其可     

JAM-C在小鼠急性坏死性胰腺炎模型不同组织中的表达

目的:研究连接黏附分子C(JAM-C)在小鼠急性坏死性胰腺炎(ANP)模型胰腺、肾脏和肺脏组织中的表达.方法:采用雨蛙素和脂多糖联合腹腔注射的方法建立小鼠ANP模型.模型组(ANP组)小鼠腹腔内注射雨蛙素(50 μg/kg),连续6次,每次间隔1 h,在末次注射雨蛙素后,即向小鼠腹腔内注射脂多糖(LPS)(10 mg/kg);对照组小鼠腹腔内注射等体积生理盐水.在末次注射3 h后,用眼球取血法收集血液,检测血清淀粉酶,并取胰腺、肾脏、肺脏组织,通过Western blot印迹杂交法检测JAM-C在这些组织上的表达.结果:JAM-C在ANP组的胰腺、肺脏和肾脏上均有着高表达,大于生理盐水对照组3倍以上(0.608±0.133 vs 0.176±0.024,0.718± 0.148 vs 0.160±0.027,0.654±0.085 vs 0.166±0.039,均P<0.05).结论:在小鼠ANP模型中,JAM-C在胰腺、肾脏和肺脏上的表达均明显增高,提示JAM-C在ANP发病过程中起到重要的作用.     

急性胰腺炎发病过程中肿瘤坏死因子受体p55/p75的表达及意义

目的探讨肿瘤坏死因子受体p55/p75(TNFR-p55/TNFR-p75)在实验性急性水肿型胰腺炎(AEP)发病机制中的作用.方法 36只雄性SD大鼠随机分为对照组与AEP组.AEP组采用雨蛙肽(20 μg/kg体重)腹腔注射,每小时1次,共4次建立大鼠急性水肿型胰腺炎模型,对照组仅给予腹腔注射生理盐水.两组大鼠分别在造模后3、6、12 h处死,收集外周血与胰腺标本.应用ELISA法检测血清TNF-α水平,运用RT-PCR的方法检测外周血单核细胞(PBMC)与胰腺组织中TNFR-p55/TNFR-p75mRNA表达,同时测定血清淀粉酶与病理组织学评分作为急性胰腺炎严重程度的指标.结果 MAP组3个时间点血清淀粉酶、TNF-α水平及胰腺组织炎症评分均显著高于对照组(P < 0.01),在PBMC及胰腺组织中TNFR-p55/TNFR-p75 mRNA的表达均显著上调(P < 0.05).结论 TNF-α是急性胰腺炎病程中的重要细胞因子并通过结合胰腺组织中TNFR-p55、TNFR-p75参与引起胰腺组织损伤;同时TNF-α通过与PBMC中 TNFR-p55/TNFR-p75相互作用导致外周血中白细胞活化,从而影响急性胰腺炎的严重程度.     

急性胰腺炎发病过程中肿瘤坏死因子受体p55／p75的表达及意义

目的探讨肿瘤坏死因子受体p55/p75(TNFR-p55/TNFR-p75)在实验性急性水肿型胰腺炎(AEP)发病机制中的作用。方法36只雄性SD大鼠随机分为对照组与AEP组。AEP组采用雨蛙肽(20μg/kg体重)腹腔注射,每小时1次,共4次建立大鼠急性水肿型胰腺炎模型,对照组仅给予腹腔注射生理盐水。两组大鼠分别在造模后3、6、12 h处死,收集外周血与胰腺标本。应用ELISA法检测血清TNF-α水平,运用RT-PCR的方法检测外周血单核细胞(PBMC)与胰腺组织中TNFR-p55/TNFR- p75mRNA表达,同时测定血清淀粉酶与病理组织学评分作为急性胰腺炎严重程度的指标。结果MAP组3个时间点血清淀粉酶、TNF-α水平及胰腺组织炎症评分均显著高于对照组(P<0.01),在PBMC及胰腺组织中TNFR-p55/TNFR-p75 mRNA的表达均显著上调(P<0.05)。结论TNF-α是急性胰腺炎病程中的重要细胞因子并通过结合胰腺组织中TNFR-1355、TNFR-p75参与引起胰腺组织损伤;同时TNF-α通过与PBMC中TNFR-p55/TNFR-p75相互作用导致外周血中白细胞活化,从而影响急性胰腺炎的严重程度。     

L-精氨酸诱导急性胰腺炎小鼠肠黏膜损伤的实验研究

目的探讨肠组织TNF-α和。ICAM-1在大剂量L-精氨酸诱导小鼠急性胰腺炎并发肠黏膜损伤机制中的作用。方法40只健康小鼠分正常对照组(15只)和胰腺炎组(25只)。给胰腺炎组小鼠腹腔注射L-精氨酸(2g/kg体重),间隔1h后同量再注射1次,对照组注射等量生理盐水。胰腺炎组在末次注射后12h采用比色法检测小鼠血清淀粉酶活性、放射免疫法测定肠组织TNF-α的含量;24h观察胰腺和肠组织病理变化并采用免疫组织化学染色法检测肠组织ICAM-1的蛋白表达。结果胰腺组织和肠组织HE染色可见典型的炎性改变;胰腺炎组小鼠肠组织TNF-α的含量、ICAM-1的表达高于对照组,且差异有显著性(P<0.05)。结论肠组织TNF-α和ICAM-1可能参与了L-精氨酸诱导的AP小鼠的肠黏膜损伤机制。     

L-精氨酸诱导急性胰腺炎小鼠肠黏膜损伤的实验研究

目的探讨肠组织TNF-α和ICAM-1在大剂量L-精氨酸诱导小鼠急性胰腺炎并发肠黏膜损伤机制中的作用.方法 40只健康小鼠分正常对照组(15只)和胰腺炎组(25只).给胰腺炎组小鼠腹腔注射L-精氨酸(2 g/kg体重),间隔1 h后同量再注射1次,对照组注射等量生理盐水.胰腺炎组在末次注射后12 h采用比色法检测小鼠血清淀粉酶活性、放射免疫法测定肠组织TNF-α的含量;24 h观察胰腺和肠组织病理变化并采用免疫组织化学染色法检测肠组织ICAM-1的蛋白表达.结果胰腺组织和肠组织HE染色可见典型的炎性改变;胰腺炎组小鼠肠组织TNF-α的含量、ICAM-1的表达高于对照组,且差异有显著性(P＜ 0.05).结论肠组织TNF-α和ICAM-1可能参与了L-精氨酸诱导的AP小鼠的肠黏膜损伤机制.     

基质金属蛋白酶抑制剂BB-94对急性胰腺炎及其相关性肺损伤的影响

目的探讨基质金属蛋白酶抑制剂对急性胰腺炎(AP)及其相关性肺损伤(APALI)的影响及其作用。方法腹腔注射L-精氮酸制备大鼠急性坏死型胰腺炎(ANP)模型。44只大鼠随机分为BB- 94(40 mg/kg/24 h,诱导AP前腹腔注射BB-94 3次)治疗组和生理盐水对照组(20 ml/kg/24 h,诱导AP 前腹腔注射生理盐水3次),每组各10只大鼠观察生存率,其余测定血清淀粉酶,胰腺和肺组织病理评分,明胶酶谱法检测MMP9和MMP2活性,检测肺脏髓过氧化酶(MPO)活性和肺血管Evans blue渗透性。结果BB-94组生存率较对照组提高(100% vs 75%),血清淀粉酶明显降低(P<0.01),肺的MMP9 和MMP2活性明显降低(P<0.01)、粒细胞浸润和蛋白渗漏明显降低(P<0.05)。结论BB-94可减轻AP时胰腺和肺脏的病理变化,降低AP所引起的肺组织MMP9和MMP2活性和蛋白渗漏。     

JAM-C单抗对小鼠急性坏死性胰腺炎的抑制作用

目的:观察JAM-C单克隆抗体对小鼠急性坏死性胰腺炎(ANP)模型胰腺和全身炎症的抑制作用.方法:采用雨蛙素和脂多糖联合腹腔注射的方法建立小鼠重症急性胰腺炎模型.生理盐水对照组(NS组):小鼠给予腹腔注射无菌生理盐水(10 mL/kg),共注射6次,间隔1 h;ANP模型组(ANP组):小鼠给予腹腔注射雨蛙素(50μg...     

Therapeutic effect of caffeic acid phenethyl ester on cerulein-induced acute pancreatitis

AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of ceruleaninduced acute pancreatitis (AP). METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 μg/kg) four times at 1-h intervals. CAPE (30 mg/kg) was given by subcutaneous injection at the beginning (CAPE 1 group) and 12 h after the last cerulein injection (CAPE 2 group). Serum amylase, lipase, white blood cell count, and tumor necrosis factor (TNF)-α levels were measured, and pancreatic histopathology was assessed. RESULTS: In the AP group, amylase and lipase levels were found to be elevated and the histopathological evaluation showed massive edema and inflammation of the pancreas, with less fatty necrosis when compared with sham and control groups. Amylase and lipase levels and edema formation decreased significantly in the CAPE therapy groups (P < 0001); especially in the CAPE 2 group, edema was improved nearly completely (P = 0001). Inflammation and fatty necrosis were partially recovered by CAPE treatment. The pathological results and amylase level in the placebo groups were similar to those in the AP group. White blood cell count and TNF-α concentration was nearly the same in the CAPE and placebo groups. CONCLUSION: CAPE may be useful agent in treatment of AP but more experimental and clinical studies are needed to support our observation of beneficial effects of CAPE before clinical usage of this agent.     

Suppression of transforming growth factor beta signalling aborts caerulein induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations

BACKGROUND: Transforming growth factors betas (TGF-betas) are implicated in pancreatic tissue repair but their role in acute pancreatitis is not known. To determine whether endogenous TGF-betas modulate the course of caerulein induced acute pancreatitis, caerulein was administered to wild-type (FVB-/-) and transgenic mice that are heterozygous (FVB+/-) for expression of a dominant negative type II TGF-beta receptor. METHODS: After 7 hourly supramaximal injections of caerulein, the pancreas was evaluated histologically and serum was assayed for amylase and lipase levels. Next, the effects of caerulein on amylase secretion were determined in mouse pancreatic acini, and cholecystokinin (CCK) receptor expression was assessed. RESULTS: The normal mouse pancreas was devoid of inflammatory cells whereas the pancreas from transgenic mice contained lymphocytic infiltrates. Caerulein injection in wild-type mice resulted in 6- and 36-fold increases in serum amylase and lipase levels, respectively, increased serum trypsinogen activation peptide (TAP) levels, gross oedema and a marked inflammatory response in the pancreas that consisted mainly of neutrophils and macrophages. By contrast, FVB+/- mice exhibited minimal alterations in response to caerulein with attenuated neutrophil-macrophage infiltrates. Moreover, acini from FVB+/- mice did not exhibit restricted stimulation at high caerulein concentrations, even though CCK receptor mRNA levels were not decreased. CONCLUSION: Our findings indicate that a functional TGF-beta signalling pathway may be required for caerulein to induce acute pancreatitis and for the CCK receptor to induce acinar cell damage at high ligand concentrations. Our results also support the concept that restricted stimulation at high caerulein concentrations contributes to the ability of caerulein to induce acute pancreatitis.     

α-硫辛酸对大鼠急性胰腺炎的保护作用及其抗氧化机制

目的探讨抗氧化剂α-硫辛酸对急性胰腺炎（AP）的治疗作用以及可能的机制。方法3．5％牛磺胆酸钠逆行胰胆管注射制备AP大鼠模型,数字表法随机分为假手术组、AP组、生理盐水组和α-硫辛酸组,每组30只。α-硫辛酸组于造模后腹腔内注射α-硫辛酸1mg／kg体重,生理盐水组注射等量生理盐水。分别于术后1、3、6、9、12h处死大鼠,检测血清淀粉酶、TNF-α、ICAM-1水平,观察胰腺病理改变,测定胰腺组织超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量。结果AP组胰腺水肿、粘连、坏死,腹腔内可见血性腹水。术后6hAP组血清淀粉酶、TNF-α、ICAM-1水平以及胰腺组织MDA含量分别为（2211．0±547．4）U／L、（174．8±7．9）ng／ml、（49．3±8．0）ng／ml和（32．2±5．9）U／mgprot,较假手术组的（160±23）U／L、（6．5±1．1）mg／ml、（13．9±3．4）mg／ml、（16．2±3．2）U／mgprot明显升高（P〈0．05）;胰腺组织SOD活力为（38．5±9．5）U／mgprot,显著低于假手术组（56．7±6．6）U／mgprot（P〈0．05）。α-硫辛酸6h组的血清淀粉酶、TNF-α、ICAM-1水平以及胰腺组织MDA含量分别为（1478±642）U／L、（164．8±6．2）ng／ml、（37．5±3．9）ng／ml和（20．2±8．4）U／mgprot,较AP组显著降低（P〈0．05）;胰腺组织SOD活力为（66．0±8．6）U／mgprot,较AP组显著升高（P〈0．05）。结论AP发病与氧化应激有关,抗氧化剂α-硫辛酸对AP大鼠具有较好的治疗作用,其机制可能与抑制TNF-α、ICAM-1活性有关。     

Acute pancreatitis-induced islet dysfunction in ferrets

Background/Objectives: The pathogenesis of hyperglycemia during acute pancreatitis (AP) remains unknown due to inaccessibility of human tissues and lack of animal models. We aimed to develop an animal model to study the mechanisms of hyperglycemia and impaired glucose tolerance in AP.MethodsWe injected ferrets with intraperitoneal cerulein (50 μg/kg, 9 hourly injections) or saline. Blood samples were collected for glucose (0, 4, 8, 12, 24h); TNF-α, IL-6 (6h); amylase, lipase, insulin, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) (24h). Animals underwent oral glucose tolerance test (OGTT), mixed meal tolerance test (MMTT) at 24h or 3 months, followed by harvesting pancreas for histopathology and immunostaining.ResultsCerulein-injected ferrets exhibited mild pancreatic edema, neutrophil infiltration, and elevations in serum amylase, lipase, TNF-α, IL-6, consistent with AP. Plasma glucose was significantly higher in ferrets with AP at all time points. Plasma glucagon, GLP-1 and PP were significantly higher in cerulein-injected animals, while plasma insulin was significantly lower compared to controls. OGTT and MMTT showed abnormal glycemic responses with higher area under the curve. The hypoglycemic response to insulin injection was completely lost, suggestive of insulin resistance. OGTT showed low plasma insulin; MMTT confirmed low insulin and GIP; abnormal OGTT and MMTT responses returned to normal 3 months after cerulein injection.ConclusionsAcute cerulein injection causes mild acute pancreatitis in ferrets and hyperglycemia related to transient islet cell dysfunction and insulin resistance. The ferret cerulein model may contribute to the understanding of hyperglycemia in acute pancreatitis.     

Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation

We studied the histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation in rats. All rats received 4 subcutaneous injections of various doses of caerulein (5-50 micrograms/kg body weight) at hourly intervals over 3 h, and 9 h after the first injection all animals were killed. Subcutaneous injections of 20 micrograms/kg body weight of caerulein induced a significant increase in serum amylase activity and histologic evidence of acute interstitial pancreatitis similar to those observed with the 50 micrograms/kg body weight dosage of caerulein. Therefore, a total of 4 subcutaneous injections of 20 micrograms/kg body weight of caerulein was chosen to study the time-course of structural and biochemical alterations in caerulein-induced acute pancreatitis. Serum amylase activity reached a maximal value of 10-fold increase over the basal values at 6 h, and then decreased gradually to normal values at 18 h after the first injection. Remarkable interstitial edema and cytoplasmic vacuoles in acinar cells were the earliest histologic alterations. Cellular infiltration was prominent at 9-12 h after the first injection. Although these histologic changes almost completely disappeared after 24 h, the reduction in the number of zymogen granules was still detectable by electron microscopic examination even after 7 days. DNA content in the pancreas showed no significant changes following the induction of acute pancreatitis, whereas a moderate to marked reduction in enzyme content persisted after 7 days. Within 14 days after the initiation of the injections, both structural and biochemical changes had completely disappeared.     

Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice

Background:

We have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of a combined treatment of galantide and octreotide with the efficacy of each agent individually in experimental AP.

Methods:

Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide and/or octreotide were co-administered with each caerulein injection commencing with the first injection. Control animals received galantide, octreotide or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma amylase and lipase activities were measured.

Results:

Galantide significantly reduced AP-induced hyperenzymaemia by 39–45%. Octreotide alone, or in combination with galantide, did not significantly alter AP-induced hyperenzymaemia. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide and octreotide administered individually reduced MPO activity by 79% and 50%, respectively; however their combination was without effect. Galantide, octreotide and their combination significantly reduced the percentage of abnormal acinar cells by 28–45%.

Conclusions:

Treatment with galantide alone ameliorated most of the indices of AP studied, whereas treatment with octreotide reduced pancreatic MPO activity and acinar cell damage. Combining the two peptides appears to negate their individual benefits, which suggests an interaction in their mechanism of action.     

Effects of nafamostat mesilate,somatostatin, and glucagon on caerulein-induced acute pancreatitis in rats

The inhibitory effects of somatostatin (SMS) and glucagon (Gn) on acute pancreatitis were evaluated in an experimental acute pancreatitis model in male Wistar rats. The effects of these agents were compared with those of nafamostat mesilate (NM). The acute pancreatitis was induced by four serial subcutaneous injections of caerulein. The rats were divided into four groups. The first group (n=28) received SMS daily, the second group (n=28) received Gn daily, and the third group (n=28) received NM daily after the first injection of caerulein. The fourth group (n=42) received caerulein alone and served as the control group. Animals were sacrificed 4, 6, 8, 12, and 24 h, and 3 and 7 days after the first administration of caerulein and the degree of severity of the acute pancreatitis was evaluated by serial morphological and histological examinations of pancreatic tissues, as well as in terms of the serum concentrations of amylase and lipase. The characteristic findings of acute pancreatitis in the animals of all groups treated with SMS, Gn, or NM were markedly attenuated at all time points after the treatments compared with findings in the controls (caerulein alone) in terms of wet weight of pancreas, serum concentrations of amylase and lipase, formation of intracellular vacuoles in acinar cells, interstitial edema, and infiltration of an inflammatory cell component. The inhibitory effects of SMS, Gn, and NM on acute pancreatitis were similar at the doses used. These results suggest that SMS and Gn are as useful as NM, they may be of value for the treatment of acute pancreatitis.     

Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation

Summary We studied the histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation in rats. All rats received 4 subcutaneous injections of various doses of caerulein (5–50 μg/kg body weight) at hourly intervals over 3 h, and 9 h after the first injection all animals were killed. Subcutaneous injections of 20 μg/kg body weight of caerulein induced a significant increase in serum amylase activity and histologic evidence of acute interstitial pancreatitis similar to those observed with the 50 μg/kg body weight dosage of caerulein. Therefore, a total of 4 subcutaneous injections of 20 μg/kg body weight of caerulein was chosen to study the time-course of structural and biochemical alterations in caerulein-induced acute pancreatitis. Serum amylase activity reached a maximal value of 10-fold increase over the basal values at 6 h, and then decreased gradually to normal values at 18 h after the first injection. Remarkable interstitial edema and cytoplasmic vacuoles in acinar cells were the earliest histologic alterations. Cellular infiltration was prominent at 9–12 h after the first injection. Although these histologic changes almost completely disappeared after 24 h, the reduction in the number of zymogen granules was still detectable by electron microscopic examination even after 7 days. DNA content in the pancreas showed no significant changes following the induction of acute pancreatitis, whereas a moderate to marked reduction in enzyme content persisted after 7 days. Within 14 days after the initiation of the injections, both structural and biochemical changes had completely disappeared. *** DIRECT SUPPORT *** A00DX035 00005     

脂蛋白脂酶基因缺陷小鼠急性胰腺炎的研究

目的 探讨应用脂蛋白脂酶基因(LPL)缺陷的杂合子小鼠作为制备高脂血症相关性急性胰腺炎的动物模型的可行性.方法 野生型及LPL杂合子小鼠均分为实验组和对照组,每组又分为12、24 h 2个时点.实验组腹腔注射雨蛙肽(50 μg/kg体重)7次,每次间隔1 h.对照组同法注射等量生理盐水.检测各组小鼠血浆三酰甘油(TG)、淀粉酶水平,观察胰腺形态学改变并评分.结果 LPL杂合子小鼠对照组血TG为(3.55±0.27)mmol/L,显著高于野生型小鼠对照组的(0.94±0.18)mmol/L(P＜0.05).杂合子小鼠实验组12 h的血TG、淀粉酶水平分别为(3.55±0.27)mmol/L和(3685±484)U/L,均显著高于野生型小鼠实验组12 h的(0.92±0.11)mmol/L和(2501±410)U/L(P＜0.05).杂合子小鼠实验组12 h的胰腺水肿、坏死、出血和炎细胞浸润的分值分别为3.94±0.21、3.94±0.21、1.84±0.25和1.84±0.25,均显著高于野生型小鼠实验组12 h的3.06±0.01、2.52±0.51、0.46±0.22和0.58±0.38(P＜0.05).结论 LPL杂合子小鼠血TG中度升高且稳定,在雨蛙肽诱导下产生严重的急性胰腺炎,是研究高脂血症相关性急性胰腺炎发病机制的一种理想的动物模型.     

急性坏死性胰腺炎大鼠腹腔内压力和血TNF-α的时相改变

目的 探讨急性坏死性胰腺炎(ANP)大鼠模型的腹腔内压力和TNF-α的时相改变及其规律.方法 80只SD大鼠按数字表法分为ANP组和对照组.采用4.5%牛磺胆酸钠胰管内逆行注射制备ANP模型,对照组注射等量生理盐水.制模后1、3、6、12、24 h分批各处死8只大鼠,检测血淀粉酶、TNF-α水平,测定腹水量和腹腔内压力,并观察胰腺病理改变.结果 ANP大鼠血淀粉酶含量呈进行性升高,24 h时高达对照组的32倍;血TNF-α水平也显著升高,6 h时达到峰值,为对照组的18倍;制模后1 h起腹水量开始增多,于24 h达到高峰,约为对照组4.7倍;制模后1 h起腹内压力明显升高,3 h时约为对照组的3倍,12 h约为对照组的9倍;胰腺病理损伤进行性加重,24 h损伤最严重.结论 ANP大鼠存在明显腹内高压,制模后12 h腹内压最高,炎症介质TNF-α升高高峰为制模后6 h,故腹内高压可能为炎症反应的后续反应.