垂体腺苷酸环化酶激活肽对胰腺及其微循环的影响

目的本实验观察外源性垂体腺苷酸环化酶激活肽(PACAP)对正常大鼠胰腺、实验性急性胰腺炎(AP)病程的影响。方法将墨汁灌注的胰腺标本切成20μm厚片 ,二甲苯透明后封片供观察。依照Schmidt-Schnbein的方法 ,以灌流毛细血管长度Lc代表FCD。将OlympusProvisAX70显微镜通过OlympusU -PMTVC与PanasonicBT -H1450Y彩色监视器相连 ,监视器上1cm=12.5μm ;将一打印了12cm×12cm大小、含100个1.2cm×1.2cm方块的网格固定于监视器屏幕。每张切片随机选取5个视野 ,计数毛细血管与网格的交叉点 ,再重复一次 ,然后计算交叉点平均值 ,以此计算灌流毛细血管长度Lc。Lc=π/2Nc/2Pd(Lc单位为cm -1;Nc=交叉点数目 ;P=网格中方块的数目 ;d=网格边缘的长度 )。结果研究发现 ,除蛙皮缩胆囊肽诱发的AP外 ,其余各组机能毛细血管密度 (Functionalcapillarydensity,FCD)均减少。5～30μg/kg的PACAP可促使血清淀粉酶轻微增高、胰腺水肿形成[胰腺干湿比 :实验组(23.88±2.532) %～(25.86±1.974) %与正常组(29.21±5.657) %]、炎性细胞浸润、腺泡细胞空泡化、部分病例可见脂肪坏死和实质坏死灶。15μg/kg和30μg/kgPACAP可加重蛙皮缩胆囊肽诱发的AP,胰腺组织水肿更明显[胰腺干湿比 :实验组(13.45±2.045)%～(17.66±4.652) %与蛙皮缩     

胰腺组织的P物质与急性胰腺炎轻重的关系

目的 研究急性胰腺炎时胰腺组织P物质的变化规律。水肿性和出血/坏死性胰腺炎时P物质水平，观察中药复方MCP-1对P物质水平的影响。方法 皮下注射蛙皮缩胆囊肽（caerulein)诱发大鼠急性水肿性胰腺炎，胆总管插管注射牛磺胆酸钠诱发急性出血/坏死性胰腺炎，以免疫组化方法检测P物质。结果 水肿性和出血性/坏死性胰腺炎，2h时SP免疫反应性明显增强，轻型和重型胰腺炎的SP免疫反应性无明显差别；MCP-1使SP免疫反应性明显减弱。结论 P物质在轻型和重型胰腺炎中所起作用相同。MCP-1可能通过降低P物质含量。发挥其抗局部微循环损伤作用。     

川芎嗪对急性胰腺炎大鼠细胞凋亡的影响

目的:研究川芎嗪(TMP)对急性胰腺炎(AP)血栓形成、组织病理变化、氧自由基和细胞凋亡的影响机制。方法:采用十二指肠胆胰管逆行加压注射5%牛磺胆酸钠的方法制备大鼠AP模型,动态观察TMP治疗前后大鼠血栓烷A2/前列环素代谢产物血栓烷B2/6-酮-前列腺素F1α(TXB2/6-Keto-PGF1α)比值(T/P)、血浆超氧化物岐化酶(SOD)、丙二醛(MDA)、淀粉酶(AMY)等各项指标;通过观察胰腺组织的病理形态进行病理评分;采用TUNEL法评价胰腺细胞凋亡指数(AI)。结果:经TMP治疗后,大鼠T/P值明显降低,血清SOD水平升高,MDA水平降低;胰腺组织病理评分为4.85±0.98(6h),AI为9.88±0.98(6h),与AP组比较差异有显著性意义(P<0.05)。结论:TMP对AP的治疗作用与其纠正血栓烷A2/前列环素I2失衡,改善AP大鼠微循环,减少自由基造成的损伤,诱导细胞凋亡,减少胰腺细胞坏死有关。     

缬草单萜氧化物对兔心室肌线粒体ATP敏感性钾通道的影响

目的 :研究缬草单萜氧化物 (VMO)对兔单个心室肌细胞线粒体ATP敏感性钾通道 (mitoKATP)的影响。方法 :采用酶解法分离单个兔心室肌细胞。实验分为 30 μg/LVMO组、6 0 μg/LVMO组、12 0 μg/LVMO组、5 羟癸酸 ( 5 HD)组和 5 HD +12 0 μg/LVMO组。用罗丹明 (Rhodamine 12 3)染色 ,激光扫描共聚焦显微镜 (多光子模式 )分别观察各组线粒体荧光强度变化。结果 :① 30 μg/LVMO组、6 0 μg/LVMO组、12 0 μg/LVMO组均可见用药后线粒体荧光强度明显增加 ,分别增加 13.90± 1.2 0 %、2 1.2 0± 2 .30 %和 2 6 .4 0± 2 .50 % ;② 50 0 μmol/L5 HD不影响线粒体荧光强度 ,但可以阻断VMO对线粒体荧光的增强效应。结论 :VMO对兔心室肌细胞mitoKATP有开放作用。     

过氧化氢对大鼠海马CA1区神经元钠电流的影响

目的与方法 :采用全细胞膜片钳技术研究过氧化氢 (H2 O2 )对急性分离的大鼠海马CA1区神经元钠电流的影响。结果 :①过氧化氢可剂量依赖地增大钠电流 ,剂量为 10 μmol/L和 10 0 μmol/L时 ,钠电流分别增大 4 8 0 %± 4 2 %和 88 2 %± 5 1% (n =10 )。② 10 μmol/L的H2 O2 不影响钠电流的激活过程 ,却非常显著地影响其失活过程 ,作用前后的半数失活电压分别为(- 6 4 5 8± 1 2 2 )mV和 (- 5 3 5 5± 0 94 )mV(n =10 ,P <0 0 1) ,但不改变失活曲线的斜率因子。结论 :H2 O2 作为体内氧化代谢产物可能与一些神经系统疾病的发生有关…     

儿童肾脏病患者血清白介素-2、白介素-6和胰岛素样生长因子-Ⅱ检测及其临床意义

为观察儿童肾脏病患者血清白介素 - 2 (IL - 2 )、白介素 - 6 (IL - 6 )、胰岛素样生长因子 -Ⅱ (IGF -Ⅱ )的含量 ,探讨细胞因子与肾脏病的关系 ,采用RIA法检测了不同肾脏病儿童患者血清IL - 2、IL - 6、IGF -Ⅱ的水平。结果显示 ,正常儿童血清IL - 2含量为 1 .6 0± 0 .32 μg/L、IL - 6为 37.0± 6 .0ng/L、IGF -Ⅱ为 0 .30±0 .1 5μg/L。正常男女性儿童之间血清三个细胞因子含量无显著性差异 (P >0 .0 5 )。正常儿童与成年人之间三个细胞因子有显著性差异 (P <0 .0 1 )。慢性肾小球肾炎血清IL - 2含量为 1 .96± 0 .4 4 μg/L、IL - 6为 5 4 .9± 2 0 .9ng/L、IGF -Ⅱ为 0 .5 2± 0 .1 5 μg/L ;急性肾炎血清IL - 2含量为 1 .92± 0 .4 7μg/L、IL - 6为 76 .3± 36 .2ng/L、IGF -Ⅱ为 0 .6 2± 0 .2 2 μg/L ;紫癜性肾炎血清IL - 2含量为 1 .91± 0 .33μg/L、IL - 6为 5 5 .5± 1 5 .1ng/L、IGF -Ⅱ为 0 .5 0± 0 .1 9μg/L ;肾病血清IL - 2含量为 1 .96± 0 .6 5 μg/L、IL - 6为 5 6 .2± 2 8.4ng/L、IGF -Ⅱ为 0 .5 9±0 .2 8μg/L ;不同肾脏病儿童三个细胞因子与正常人相比有显著差异 (P <0 .0 1 )。提示 :不同肾脏病儿童血清IL- 2、IL - 6、IGF -Ⅱ含量升高表明 ,这三个细胞因子均积极参与     

人胰腺导管上皮细胞的原代和传代培养

目的　完成胰腺导管上皮细胞的原代及传代培养 ,建立能够体外长期培养的胰腺导管上皮细胞系。　方法　用含有胶原酶 IA型的消化液消化分离胎儿胰腺组织为细小、均匀的细胞团进行接种 ,接种的细胞团用含10 %胎牛血清、4.0 m mol/L谷氨酰胺、0 .0 1%大豆胰酶抑制剂、0 .0 2 %牛血清白蛋白、5 .0 m g/L牛脑垂体提取物、2 .5× 10 - 3m g/L表皮生长因子、2 5 .0× 10 - 2 m g/L霍乱毒素、5 .0 mg/L胰岛素、10 .0 mg/L转铁蛋白、1.0 m g/L地塞米松、5 0 m g/L庆大霉素的完全培养基培养 2 4h后 ,换含 2 %胎牛血清的完全培养基继续培养 ,在细胞团达到 80 %～ 90 %的细胞汇合时 ,1∶ 2传代培养。　结果　获得的原代培养细胞不含有淀粉酶 ,表达细胞角蛋白 ,可初步认定为胰腺导管上皮细胞。原代培养的胰腺导管上皮细胞已传代培养到第 3代。　结论　我们的原代培养和传代培养的方法、条件适宜于胰腺导管上皮体外细胞培养。     

血清甘露聚糖凝集素水平及与反复呼吸道感染关系的初步研究

目的　建立儿童血清甘露聚糖凝集素 (MBL)水平正常值参考范围 ,了解血清MBL低水平与反复呼吸道感染的关系。方法　用ELISA方法检测重庆地区 91例新生婴儿脐血MBL水平 ,2 6 3例学龄前儿童、1 6例成人血清MBL水平 ,并对学龄前各年龄组血清低MBL水平的儿童进行反复呼吸道感染的病史回顾。结果　新生儿脐血MBL水平为 ( 1 .71± 1 .6 0 ) μg/ml,成人外周血 ( 2 .2 6± 1 .56 ) μg/ml,两组比较差异无统计学意义 (P >0 .0 5) ,学龄前各年龄组MBL水平分别为 ( 3.1 6±2 .0 0 ) μg/ml、( 3.1 9± 1 .88) μg/ml、( 3.30± 2 .0 5) μg/ml、( 3.6 9± 2 .2 2 ) μg/ml、( 2 .80± 1 .38) μg/ml,与新生儿比较明显增高 (P <0 .0 0 5) ,但学龄前期各组间比较差异无统计学意义 (P >0 .0 5) ;1 6例血清低MBL水平儿童中 7例在 3岁前出现反复呼吸道感染 ( 4 3.7% ) ,主要感染方式为上呼吸道感染 ,血清MBL水平低于 1 0 0ng/ml组与血清MBL水平在 1 0 0～ 2 0 0ng/ml的儿童比较反复呼吸道感染频率有增多趋势。结论　新生儿期MBL水平可达成人水平 ,但明显低于学龄前各年龄组儿童 ,学龄前儿童组间比较没有显著差异 ;低血清MBL水平儿童在免疫脆弱阶段存在反复呼吸道感染的易患倾向 ,血清MBL水平下降时 ,呼吸道感染频率有增     

VEGF165对兔动脉粥样硬化斑块影响的实验研究

目的观察VEGF165对动脉粥样硬化斑块形成与发展的影响.方法利用高胆固醇饲料复制动脉粥样硬化兔模型.15只日本大耳白兔随机分为3组,A组,阴性对照组,仅给普通饲料喂养,B、C组给高胆固醇饲料喂养,喂养到第3周(21 d),A组及B组肌注白蛋白(2 μg/kg),C组肌注VEGF165(2 μg/kg),继续以前的方式饲养3周(42 d)处死动物,截取胸主动脉进行计量组织学及免疫组织化学分析.结果 (1)斑块面积(A组 0%,B组 1.81%±0.61%,C组 24.12%±3.58%),斑块周径(A组 0,B组 6.05%±1.62%, C组 25.71%±1.97%)及斑块最大厚度(A组 0,B组0.06 mm±0.002 mm, C组 0.16 mm±0.007 mm),三组之间相比有显著性差异(P＜0.05);(2)新生血管密度[CD34阳性细胞数(cells/mm2)A组0, B组 12.35±2.02, C组 61.15±7.55]各组之间比较有显著性差异(P＜0.05);(3)电镜显示新生血管与动脉粥样斑块相邻,新生血管腔内可见淋巴细胞;(4)VEGF组CD34阳性细胞数与斑块面积之间呈正相关(r=0.989,P＜0.001).结论 VEGF165能促进兔动脉粥样硬化斑块的形成与发展.     

体外循环与抗血栓形成血浆C蛋白的激活

目的　我们假设血浆激活的抗血栓形成 C蛋白在冠状动脉缺血及缺血后再灌注过程中起防御性的抗血栓形成功能。方法及结果　测定 2 0例冠状动脉旁路术患者体外循环及冠状动脉再灌注期间 C蛋白的激活程度 ,在心肺转流期间及主动脉开放后 10 min,血浆 C蛋白水平从正常均数 ( M SE)的 12 3 %± 7%降至 74%± 5 % ;相反 ,血浆中激活 C蛋白水平从 12 2 %± 8%上升至 15 9%± 2 1% ,激活 C蛋白 /C蛋白比例从 1.0 4± 0 .0 8增加到 2 .2 9± 0 .3 1( P=0 .0 0 6)。以再灌注 10 min后冠状窦血浆激活 C蛋白 /C蛋白比例 1.5作人为标准 ,对患者激活 …     

Platelet-activating factor: a mediator of pancreatic inflammation during cerulein hyperstimulation.

Hyperstimulation of the exocrine pancreas with cerulein causes acute pancreatitis, characterized by intensive interstitial edema, acinar vacuolization, leukocytic infiltration, and hyperamylasemia. Whereas the pathogenesis of cerulein-induced pancreatitis is not well-defined, a local inflammatory response may contribute to the full expression of acute pancreatitis. Platelet-activating factor (PAF) seems to be an important mediator of the inflammatory response. The present evidence includes: 1) pancreatic PAF levels increased in rats in which cerulein-induced pancreatitis was initiated, concomitant with an increase in calcium concentrations in the pancreatic tissue; 2) treatment of rats exposed to cerulein with WEB2170, a PAF receptor antagonist, was shown to reduce inflammatory injury, as demonstrated by decreases in pancreatic weight, Evan's blue extravasation, and myeloperoxidase activity and an improvement in pancreatic histology. In an idealized in vitro experiment mimicking cerulein-induced acute pancreatitis, in which pancreatic acini were employed, cerulein induced amylase release, an increase in [Ca2+]i, and an increase in PAF synthesis. Whereas amylase release was induced by low concentrations of cerulein (10(-11) mol/L), relatively high concentrations of cerulein (10(-9) mol/L) were required for the observed increases in PAF synthesis and the [Ca2+]i, indicating that these two responses may not occur under physiological conditions. The present study suggests that the pancreatic accumulation of PAF coupled with Ca2+ overload are important biochemical components of the pathophysiology of cerulein-induced acute pancreatitis. In fact, PAF production may serve as a primary mediator of inflammation observed during pancreatic hyperstimulation. This is an important observation that will allow a more detailed characterization of the molecular basis of cerulein-induced acute pancreatitis.     

Oxidative stress is enhanced by hypothermia imposed on cerulein-induced pancreatitis in rats

BACKGROUND: Hypothermia is a frequent event in severe acute pancreatitis (AP) and its real effects on the normal pancreas have not been well demonstrated. Moreover, neither have its effects on the outcome of acute pancreatitis been fully investigated. One hypothesis is that oxidative stress may be implicated in lesions caused or treated by hypothermia. AIM OF THE STUDY: To investigate the effect of hypothermia in cerulein-induced acute pancreatitis (CIAP) in rats and the role played by oxidative stress in this process. METHODS: Male Wistar rats were divided into hypothermic and normothermic groups. Hypothermia was induced with a cold mattress and rectal temperature was kept at 30 masculineC for one hour. Acute pancreatitis was induced with 2 doses of cerulein (20 ìg/kg) administered at a one-hour interval. Serum amylase, pancreas vascular permeability by Evan's blue method, pancreas wet-to-dry weight ratio and histopathology were analyzed in each group. RESULTS: When compared with normothermic rats, hypothermic animals, with cerulein-induced acute pancreatitis, showed higher levels of pancreatic vascular permeability (p < 0.05), pancreas wet-to-dry weight ratio (p = 0.03), and histologically verified edema (p < 0.05), but similar serum amylase levels. The hypothermic group showed a higher oxidized-reduced glutathione ratio than the normothermic group. CONCLUSION: Moderate hypothermia produced a greater inflammatory response in established acute pancreatitis induced by cerulein in rats. Moreover, this study suggests that oxidative stress may be one of the mechanisms responsible for the worse outcome in hypothermic rats with cerulein-induced acute pancreatitis.     

Role of macrophage inflammatory peptide-2 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury

Acute pancreatitis is an inflammatory process of variable severity, and leukocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The effects of mediators released by these inflammatory cells may induce tissue damage. The aim of our study was to evaluate the role of the chemokine, macrophage inflammatory protein-2 (MIP-2), in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. The severity of pancreatitis was measured by serum amylase, pancreatic edema, acinar cell necrosis, and myeloperoxidase activity. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. To determine the role of MIP-2 in the pathophysiology of the disease, anti-MIP-2 antibody was administered either 1 hour before or 2 hours after the start of cerulein administration. MIP-2 concentrations increased in serum, pancreas, and lung tissues in mice treated with cerulein. Anti-MIP-2 antibody administrated either before or after cerulein partially protected against pancreas and lung injury. These results show that MIP-2 plays a key role in the pathophysiology of acute pancreatitis and that MIP-2 blockade may improve the outcome of the disease.     

Protective effects of Curcuma longa against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury

Curcuma longa (CL) has been reported to possess a variety of pharmacological activities. However, the effects of CL on acute pancreatitis (AP) have not yet been determined. To this end, we examined the effects of CL on cerulein-induced AP. Cell viability and cytokine productions were measured in pancreatic acini. Mice were divided into 3 groups: i) Normal group, ii) normal saline-treated group, iii) group treated with CL at a dose of 0.05, 0.1, 0.5 and 1 g/kg. CL was administered orally to mice for 7 days. The mice were intraperitoneally injected with the stable cholecystokinin analogue, cerulein (50 μg/kg), every hour for a total of 6 h. The mice were sacrificed 6 h after the completion of the cerulein injections. Blood samples were obtained to determine serum amylase, lipase and cytokine levels. The pancreas was rapidly removed for morphological examination, measurement of tissue myeloperoxidase activity, as well as the level of cytokines and heme oxygenase-1 (HO-1). The CL treatment reduced cerulein-induced cell death and cytokine production in pancreatic acini. The administration of CL significantly ameliorated the severity of pancreatitis and pancreatitis-associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization, necrosis, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as interleukin (IL)-1? and -6 and tumor necrosis factor (TNF)-α. In order to identify the regulatory mechanism of CL on cerulein-induced pancreatitis, we examined the level of HO-1 in the pancreas. We found that the administration of CL induced HO-1. Our results suggest that CL plays a protective role in the development of AP and pancreatitis-associated lung injury.     

Effects of methimazole pretreatment on cerulein induced acute pancreatitis in rats.

BACKGROUND: Many interrelationships exist between the thyroid gland and the gastrointestinal tract. Several past and recent studies have shown that the thyroid gland profoundly influences the structure and function of the exocrine pancreas in the rat. In the present study we investigated the effect of methimazole (METZ), an antithyroid drug, on cerulein induced acute pancreatitis (AP) in rats. METHODS: Rats were divided into 3 groups (10-12 weeks age, 200-250 g weight, n: 10). Group B was made hypothyroid with methimazole 5 mg/kg daily for 10 days and the others were untreated euthyroid groups. After 10 days, acute pancreatitis was induced with four doses of 20 microg/kg body weight of cerulein administered s.c at hourly intervals in group A and B while the control group C was given 4 doses of I ml saline. Pancreas wet weight (mg), plasma amylase activity (IU/l) and pancreatic histology were used as endpoints to quantify the severity of the AP. RESULTS: Plasma tri-iodothyronine (T3) (ng/dl) and thyroxine (T4) (microg/dl) levels were significantly reduced after METZ treatment for 10 days (p < 0.01). METZ pretreatment reduced significantly the cerulein induced increase in pancreatic weight (1,205 +/- 12 mg in METZ treated AP group versus 1,617 +/- 14 mg in AP group, p < 0.05) and the rise in amylase activity (7,078 +/- 816 IU/l in METZ treated AP group versus 8,611 +/- 830 IU/l in AP group p < 0.05). CONCLUSION: METZ reduces the severity of cerulein induced AP in rats. This effect might be through its antithyroid property.     

Attenuated cerulein-induced pancreatitis in nuclear factor-kappaB-deficient mice

Nuclear factor (NF)-kappaB plays a central role in acute pancreatitis. We studied cerulein (CER)-induced pancreatitis in NF-kappaB knockout (KO) mice. NF-kappaB KO mice and normal control littermate wild-type (WT) mice were given four hyperstimulating doses of cerulein every hour to elicit secreatagogue-induced pancreatitis. Malonildialdehyde activity, glutathione levels, myeloperoxidase activity, TNF-alpha, and NF-kappaB binding activity and its inhibitory protein IkappaBalpha were studied in the pancreas. Furthermore, we measured plasma lipase and amylase and the histological damage. KO mice had reduced malonildialdehyde levels (WT + CER = 4.083 +/- 0.95 micromol/g; KO + CER = 1.513 +/- 0.63 microol/g), decreased myeloperoxidase activity (WT + CER = 19.3 +/- 2.39 mU/g; KO + CER = 10.21 +/- 2.05 mU/g), increased glutathione levels (WT + CER 6.22 +/- 2.46 micromol/g; KO + CER = 15. 516 +/- 2.92 micromol/g), and reduced serum levels of amylase (WT + CER = 2519 +/- 656.9 U/L; KO + CER = 916 +/- 280.4 U/L) and lipase (WT + CER = 1420 +/- 170 U/L; KO + CER = 861 +/- 172. 3 U/L). KO mice showed reduced pancreatic NF-kappaB activation, decreased TNF-alpha tissue content, and reduced histologic alterations. Our data suggest that KO mice have an attenuated cerulein-induced pancreatitis and help to define the possible interaction between NF-kappaB activation and oxidative stress in this deleterious event.     

The role of nitric oxide in experimental cerulein induced pancreatitis

An enhanced formation of nitric oxide (NO), due to the induction of inducible nitric oxide synthase (iNOS), has been implicated in the pathogenesis of shock and inflammation, but its role in acute pancreatitis still remains controversial. To clarify the role of NO in acute pancreatitis, the present experiment investigated the expression of iNOS and the effect of NOS inhibition on cerulein-induced pancreatitis in rats. Group I received intraperitoneal (ip) injection of normal saline. Group II received two ip injections of cerulein (20 microgram/kg). Group III received injections of N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg) with cerulein. Group IV received L-arginine (250 mg/kg) with cerulein and L-NAME. The expression of iNOS in the pancreas was examined by western blot analysis. The plasma concentration of NO metabolites was measured. The severity of pancreatitis was assessed by measuring serum amylase, pancreas water content and histopathological examination. Compared with controls, the cerulein group displayed significantly increased expression of iNOS and raised plasma NO metabolites. Treatment with L-NAME significantly decreased hyperamylasemia, plasma NO level, and the extent of pancreatic injury. Treatment with L-arginine reversed the effects of L-NAME. These findings suggest that an enhanced formation of NO by iNOS plays an important role in the development of acute pancreatitis, and inhibition of NO production has the beneficial effects in reducing pancreas injury.     

Experimental acute pancreatitis induced by platelet activating factor in rabbits.

This study indicates that a single injection of platelet activating factor (PAF, 50-500 ng) into the superior pancreaticoduodenal artery of rabbits induces dose-dependent morphologic alterations of pancreatic tissue and increases serum amylase levels, both consistent with the development of an acute pancreatitis. The main histologic findings observed by light microscopy 24-72 hours after the injection of PAF were edema, polymorphonuclear neutrophil infiltration, cell vacuolization, and acinar cell necrosis. Fat cell necrosis was present in 30% of animals. By electron microscopy an increase of the number of zymogen granules in the apical region of acinar cells was observed 3 hours after PAF challenge. At 24-72 hours, many acinar cells showed vacuoles containing myelinlike figures, zymogen granules, and cellular debris. Pancreatic lesions developed in the area supplied by the artery injected with PAF and they were completely antagonized by the pretreatment of rabbits with CV 3988, a specific antagonist of PAF. In addition, the significant protective effect of atropine suggests a potential role for cholinergic mechanisms in the pancreatic alterations induced by PAF.     

Diosmetin ameliorates the severity of cerulein-induced acute pancreatitis in mice by inhibiting the activation of the nuclear factor-κB

Diosmetin (3’, 5, 7-trihydroxy-4’-methoxyflavone), the aglycone part of the flavonoid glycosides diosmin occurs naturally in citrus fruit, was considered to exhibit anti-inflammatory and antioxidant properties. Our study aimed to investigate the effect of diosmetin in a murine model of cerulein-induced acute pancreatitis (AP). Experimental AP was induced in mice by seven intraperitoneal injection of cerulein (50 ug/kg) at hourly intervals. Diosmetin (100 mg/kg) or vehicle was pretreated 2 h before the first cerulein injection. After 6 h, 9 h, 12 h of the first cerulein injection, the severity of acute pancreatitis was evaluated biochemically and morphologically. Pretreatment with diosmetin significantly reduced serum levels of amylase and lipase; the histological injury; the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6; myeloperoxidase (MPO) activity, trypsinogen activation peptide (TAP) level, the expression of inducible nitric oxide synthase (iNOS); and the nuclear factor (NF)-κB activation in cerulein-induced AP. This study showed that administration of diosmetin demonstrated a beneficial effect on the course of cerulein-induced AP in mice. Therefore, diosmetin may become a new therapeutic agent in future clinical trials for treatment of AP.