经空肠内营养对急性胰腺炎犬胰液分泌、氨基酸摄取和酶蛋白合成的影响

目的探讨经空肠内营养(EIN)对急性胰腺炎犬胰液分泌、腺泡细胞氨基酸摄取及亚细胞成分中酶蛋白合成的影响.     

奥曲肽对急性坏死性胰腺炎炎症介质的调节作用

目的 观察奥曲肽对急性坏死胰腺炎（ＡＮＰ）大鼠肿瘤坏死因子ａ（ＴＮＦａ）、一氧化氮（ＮＯ）和内毒素等炎症介质的影响,并探讨其对ＡＮＰ大鼠的治疗作用。方法 ＳＤ大鼠９３只,随机分为３组：ＡＮＰ生理盐水处理组（ＡＮＰ＋ＮＳ组）、ＡＮＰ奥曲肽治疗组（ＡＮＰ＋奥曲肽组）和假手术组（ＳＯ组）。观察各组大鼠的平均存活时间和存活率、血清淀粉酶活性、腹水量、胰腺系数及病理形态变化;测定血浆内毒素、血清ＴＮＦａ及血     

塞来昔布对大鼠胰腺腺泡细胞炎症损伤的作用

背景：急性胰腺炎（AP）的发病始于胰腺腺泡细胞内胰酶的激活,造成腺泡细胞损伤。环氧合酶-2（COX-2）和核因子-κB（NF．KB）在AP的炎症反应中起重要作用。目的：观察雨蛙肽和选择性COX-2抑制剂塞来昔布对离体大鼠胰腺腺泡细胞COX-2和NF—κB表达的影响．探讨塞来昔布对腺泡细胞炎症损伤的作用。方法：分离大鼠胰腺腺泡细胞,分为对照组、雨蛙肽组（1×10^-7mol／L）和塞来昔布干预组（100μmol／L,15min后加入雨蛙肽）,分别培养1、3、6、12h。测定腺泡细胞活力、淀粉酶分泌率和乳酸脱氢酶（LDH）漏出率,逆转录聚合酶链反应（RT-PCR）和免疫细胞化学染色检测COX-2、NF—κBmRNA和蛋白表达。结果：与对照组相比,雨蛙肽组各时间点腺泡细胞活力均显著降低,淀粉酶分泌率和LDH漏出率显著增高,COX-2和NF—κBmRNA表达量显著增高,蛋白表达阳性率亦增加（P〈0．05）。塞来昔布干预组各时间点腺泡细胞活力、淀粉酶分泌率和LDH漏出率均较雨蛙肽组显著改善（心O．05）,COX-2mRNA和蛋白表达显著降低（P〈0．05）,NF—κBmRNA和蛋白表达与雨蛙肽组无明显差异。结论：塞来昔布可抑制大鼠胰腺腺泡细胞中雨蛙肽刺激的COX-2活性,从而减轻细胞炎症损伤。     

大黄对大鼠急性出血性胰腺炎的影响

目的 观察中药大黄对大鼠急性出血性胰腺炎的作用以及对胰腺外分泌功能的影响。方法 采用铃蟾肽加水浸束缚应激的方法诱导大鼠急性出血性胰腺炎，经口灌服大黄醇抽提物75～150mg／kg2次。观察血清淀粉酶、胰腺湿重、胰腺血流量及胰腺组织病理改变；并观察大黄与奥曲肽对胰液外分泌功能的影响。结果 大黄治疗组的胰腺坏死和中性粒细胞浸润明显减轻；胰腺湿重、血清淀粉酶活性和胰腺血流量均有剂量依赖性改善。胰腺炎组大鼠胰液流量、胰液蛋白含量均明显下降，胰液碳酸氢根含量没有明显改变，大黄治疗组胰液淀粉酶活性明显降低，与奥曲肽治疗组比较无统计学差异，其胰液碳酸氢根含量明显升高，奥曲肽则无此作用。结论 大黄可有效改善大鼠急性出血性胰腺炎的严重程度，与抑制胰腺炎性反应、改善胰腺血流量和抑制胰酶分泌、促进胰液引流等多靶位作用有关。     

奥曲肽对糖尿病大鼠胰岛形态及α、β细胞数量的影响

目的探讨奥曲肽治疗糖尿病的可行性。方法将32只糖尿病模型大鼠随机分为模型组、奥曲肽组、胰岛素组和联合组各8只,另取8只正常大鼠作为正常组。奥曲肽组、胰岛素组及联合组分别皮下注射奥曲肽、甘精胰岛素及奥曲肽+甘精胰岛素治疗;模型组及正常组皮下注射等量生理盐水。干预4周后处死大鼠,取胰腺组织HE染色观察胰腺内胰岛数量与大体形态,采用免疫组化的方法观察单个胰岛中主要内分泌细胞(α、β细胞)数量以及分布。结果与模型组比较,奥曲肽组、胰岛素组和联合组胰腺中胰岛数量较多,形态较规则,边缘较整齐,尤以奥曲肽组和联合组明显;但四组均明显少于正常组。单个胰岛中β细胞数量正常组>联合组>奥曲肽组>胰岛素组>模型组,P均<0.05。奥曲肽组、胰岛素组和联合组单个胰岛α细胞数量均明显高于模型组,P均<0.05;但均少于正常组,P均<0.05。α、β细胞数量比值正常组与联合组比较、联合组与奥曲肽组组比较,模型组与胰岛素组比较,P均>0.05,其余各组间比较P均<0.05。结论奥曲肽可以提高单个胰岛内α、β细胞数量,降低α、β细胞数量比值,减轻STZ导致的糖尿病大鼠胰岛的病理损害。     

高三酰甘油血症对大鼠胰腺腺泡细胞的影响

目的 研究高三酰甘油血症对大鼠胰腺腺泡细胞形态和功能的影响.方法 断奶1周雄性SD大鼠(约70 g)随机分为2组,每组10只,分别给予高脂饲料和普通饲料喂养4周.检测血清三酰甘油(TG)、胆固醇(TC)及游离脂肪酸(FFA)水平,HE染色和透射电镜观察胰腺腺泡细胞形态.胶原酶消化法分离大鼠胰腺腺泡细胞,台盼蓝染色测定细胞活力.给予不同浓度胆囊刺激素(CCK-8)刺激胰腺腺泡细胞分泌淀粉酶及乳酸脱氢酶(LDH),测定酶释放率. 结果 高脂饮食饲喂大鼠4周后,血清TG、FFA较正常饮食组明显升高(P ＜ 0.05).高脂饮食组大鼠胰腺腺泡细胞出现空泡样改变及内质网扩张.体外培养6 h后,高脂饮食组胰腺腺泡细胞活力低于对照组(P ＜ 0.05),且各浓度CCK-8引起的淀粉酶和LDH释放均高于正常饮食组(P ＜ 0.05).结论 饮食诱导的高三酰甘油血症可以引起大鼠胰腺腺泡细胞损伤.     

高三酰甘油血症对大鼠胰腺腺泡细胞的影响

目的研究高三酰甘油血症对大鼠胰腺腺泡细胞形态和功能的影响。方法断奶l周雄性SD大鼠（约70g）随机分为2组．每组10只．分别给予高脂饲料和普通饲料喂养4周。检测血清三酰甘油（TG）、胆固醇（TC）及游离脂肪酸（FFA）水平，HE染色和透射电镜观察胰腺腺泡细胞形态。胶原酶消化法分离大鼠胰腺腺泡细胞．台盼蓝染色测定细胞活力。给予不同浓度胆囊刺激素（CCK-8）刺激胰腺腺泡细胞分泌淀粉酶及乳酸脱氢酶（LDH）．测定酶释放率。结果高脂饮食饲喂大鼠4周后，血清TG、FFA较正常饮食组明显升高（P〈0．05）。高脂饮食组大鼠胰腺腺泡细胞出现空泡样改变及内质网扩张。体外培养6h后，高脂饮食组胰腺腺泡细胞活力低于对照组（P〈0．05），且各浓度CCK-8引起的淀粉酶和LDH释放均高于正常饮食组（P〈0．05）。结论饮食诱导的高三酰甘油血症可以引起大鼠胰腺腺泡细胞损伤。     

棕榈酸对雨蛙肽诱导的大鼠胰腺腺泡细胞炎症早期基因表达谱的影响

背景：高三酰甘油血症是急性胰腺炎的发病原因之一。血浆中增多的游离脂肪酸（FFA）可损伤多种细胞，导致细胞功能障碍，可能在高三酰甘油血症性急性胰腺炎的发生、发展中起重要作用。目的：探讨饮食中的主要FFA棕榈酸对雨蛙肽诱导的大鼠胰腺腺泡细胞炎症早期基因表达谱的影响。方法：以胶原酶消化法分离大鼠胰腺腺泡细胞，将细胞分为3组，雨蛙肽组加入终浓度为100nmol／L的雨蛙肽，雨蛙肽＋棕榈酸组加入相同剂量的雨蛙肽和终浓度为1mmol/L的棕榈酸，正常对照组不予处理。培养3h后提取细胞总RNA，应用含15000余条大鼠基因的大鼠Affymetrix 230A基因芯片检测基因表达谱的变化。结果：雨蛙肽＋棕榈酸组较雨蛙肽组出现30条上调基因和15条下调基因，其功能涉及细胞信号转导、转录、脂质代谢、蛋白修饰等不同层次。结论：棕榈酸可能通过影响大鼠炎症胰腺腺泡细胞多种结构和功能基因的表达而加重其损伤。     

急、慢性胰腺炎发病机制的最早阶段变化

胰腺腺泡是胰腺炎最早发生形态学变化的场所,当摄取高脂肪、高蛋白及大量饮酒的食糜进入小肠时,十二指肠Ⅰ型细胞即分泌胆囊收缩素(CCK),迅速激活了腺泡内的酶原颗粒,其中胰蛋白酶原受蛋白分解酶肠激酶的作用转变为具活性的     

急、慢性胰腺炎发病机制的最早阶段变化

胰腺腺泡是胰腺炎最早发生形态学变化的场所，当摄取高脂肪、高蛋白及大量饮酒的食糜进入小肠时，十二指肠Ⅰ型细胞即分泌胆囊收缩素(CCK)，迅速激活了腺泡内的酶原颗粒，其中胰蛋白酶原受蛋白分解酶肠激酶的作用转变为具活性的胰蛋白酶，然后胰蛋白酶又将前弹力酶、羧基肽酶原、非活性型磷脂酶A2激活转变为其活性型。生     

Mechanism of octreotide in acute necrotizing pancreatitis (ANP) of rats: An experimental study

OBJECTIVE : To study the action of octreotide in acute necrotizing pancreatitis (ANP) in rats. METHODS : The effect of octreotide on pancreatic acinar cells with respect to amino acid uptake, protein synthesis and secretion of enzymes was observed by using radioactive tracing and autoradiography on both healthy rats and rats with ANP. RESULTS : It was shown that octreotide has no effect on pancreatic acinar cells with respect to amino acid uptake and protein synthesis in both ANP and in control rats. However, octreotide was able to inhibit the secretion of enzyme‐proteins. There were secretions from the basolateral membrane of the acinar cells in ANP rats, which could be reduced by treatment with octreotide. CONCLUSIONS : Octreotide has no effect on pancreatic acinar cells with respect to amino acid uptake and enzyme‐protein synthesis, but it can inhibit the secretion of enzyme‐proteins, in particular, from the basolateral membrane of ANP rats and prevent the accumulation of zymogen granules in the interstitium.     

Effect of octreotide, a long-acting somatostatin analogue, on plasma amino acid uptake by the pancreas.

Octreotide (SMS 201-995) is a long-acting somatostatin analogue that inhibits exocrine pancreatic secretion and that has been proposed for treatment of various pancreatic disorders. To gain more information about the mechanism by which octreotide inhibits pancreatic enzyme secretion, we studied the effect of this compound on plasma amino acid uptake by the pancreas in six healthy volunteers aged 22-29 years. Pancreatic amino acid uptake was assessed by measuring plasma amino acid concentration before and during pancreatic enzyme synthesis stimulation with cerulein (50 ng/kg/h). The infusion of cerulein caused a significant decrease (p less than 0.001) in plasma amino acid concentration. The subcutaneous injection of octreotide at dosages of 12.5, 25, and 50 micrograms prevented this decrease in a dose-dependent manner. The decrease in amino acid concentration reached a maximum of 19.4 +/- 2.4% during cerulein infusion and a maximum of 10.7 +/- 2.5, 6.8 +/- 1.2, and 2.9 +/- 1.2% (means +/- SD) when cerulein was preceded by injection of octreotide at 12.5, 25, and 50 mg, respectively. These results indicate that octreotide is able to inhibit the plasma amino acid uptake by pancreatic acinar cells and, consequently, synthesis of pancreatic enzymes. Clinically, this effect could be useful in treatment of pathologic conditions of the pancreas in which it is desirable to suppress acinar cell activity and avoid accumulation of enzymes in acinar cells.     

Effect of somatostatin on plasma amino acid uptake by human pancreas

We studied the effect of somatostatin on amino acid uptake by pancreatic acinar cells in 12 healthy male volunteers, aged 20-48 yr. Pancreatic amino acid uptake was assessed by measuring free plasma amino acid concentration before and during pancreatic stimulation with secretin (1 CU/kg body wt.h) and cerulein (50 ng/kg body wt.h). Pancreatic stimulation with these peptides caused a significant decrease in plasma amino acid concentrations. Somatostatin, given at the dosages of 0.15 and 1.35 micrograms/kg body wt.h, significantly diminished this decrease. The effect of the higher dose of somatostatin was more marked than that produced by the lower dose, compatible with dose dependence. The results suggest that somatostatin is able to inhibit the amino acid uptake by the pancreatic acinar cells. This inhibitory effect could be an important mechanism by which the peptide decreases pancreatic enzyme secretion.     

Pancreatic lysosomal enzyme secretion is changed by hepatectomy in rats.

To explore the effect of hepatectomy on the secretion of lysosomal enzymes into the pancreatic juice when stimulated by gut hormones, we evaluated the cerulein-stimulated amylase output and cathepsin B output into pancreatic juice, the amylase and cathepsin B content in pancreatic tissue, and the distribution of cathepsin B in acinar cells in the regenerating (4 days) and recovering (8 days) stages after about 70% hepatectomy in rats. Amylase output was significantly higher after hepatectomy than in the control groups. Cathepsin B was secreted into the pancreatic juice after stimulation by cerulein in both the control and the hepatectomized groups, but, particularly 4 days after hepatectomy, cathepsin B output was significantly higher than in the controls, and in the acinar cells redistribution of cathepsin B was found. These changes in cathepsin B disappeared in the recovery stage (8 days) after hepatectomy. In addition, the amylase content in pancreatic tissue was significantly greater in the hepatectomized than in the control rats, but the cathepsin B content did not show any significant change. These results indicate that cerulein can stimulate the secretion of lysosomal enzyme into the pancreatic juice, as it does the secretion of digestive enzymes. Moreover, it appears that the synthesis and secretion of amylase in and from the acinar cells is increased after hepatectomy and that a redistribution of lysosomal enzyme occurs in the acinar cells.     

Effect of pancreatic polypeptide, thyrotropin-releasing hormone, and glucagon on plasma amino acid uptake by human pancreas

The effects of pancreatic polypeptide, thyrotropin-releasing hormone, and glucagon on plasma amino acid uptake by the exocrine pancreas were studied in 12 healthy volunteers aged 22-31 years. Pancreatic amino acid uptake was determined by measuring free plasma amino acid concentration before and during pancreatic stimulation with cerulein (50 ng/kg.h). The administration of this peptide caused a significant decrease (by 14%-20%) in plasma amino acid concentration. Pancreatic polypeptide and thyrotropin-releasing hormone, given at respective doses of 195 pmol/kg.h and 2 micrograms/kg.h, significantly prevented this decrease by 79.3% and 55.8%, respectively. Glucagon, administered at a dose of 7.5 micrograms/kg.h, significantly augmented (by 68.8%) the decreasing effect of cerulein on plasma amino acid concentration. In 2 patients with severe exocrine pancreatic insufficiency, cerulein had no effect on the concentration of plasma amino acids, whereas the addition of glucagon caused a marked decrease. The results indicate that pancreatic polypeptide and thyrotropin-releasing hormone are able to inhibit plasma amino acid uptake by pancreatic acinar cells; this inhibitory effect could be a mechanism by which these peptides decrease pancreatic enzyme secretion. Glucagon does not seem to affect pancreatic amino acid uptake, at least not under the experimental conditions of this study. The decrease in plasma amino acid concentration following glucagon administration was likely the result of the stimulation of amino acid uptake by extrapancreatic tissues by this peptide.     

Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal rats and rats with acute edematous pancreatitis

Pancreatic enzyme secretion is inhibited during acute pancreatitis, resulting in an increase in acinar zymogen content. Since the premature activation of zymogens has been assigned a central role in the pathogenesis of acute pancreatitis, minimizing the amount of stored zymogens might lead to less severe acute pancreatitis. Inhibition of enzyme synthesis or stimulation of enzyme secretion would result in reduction of zymogen stores. Opiates have a varying effect on pancreatic secretion, depending on the dosage, site of administration, and presence of pancreatic stimulants. The effect of opiates and acute pancreatitis on individual pancreatic enzyme synthesis is unknown. The following study was undertaken in order to examine the effects of an opiate on pancreatic enzyme secretion and synthesis during experimental acute pancreatitis. Four groups of rats were studied. Group I received cerulein (25 µg/kg); group II received an opiate, buprenorphine (BPN, 0.5 mg/kg); and group III received cerulein and BPN. Drugs were dissolved in gelatin/saline and injected subcutaneously. A control group (group IV) received only gelatin/saline. Rats were sacrificed 4 hr after injection, and pancreatic mass was measured. Pancreatic acini were prepared and assayed for amylase and DNA content. Amylase, trypsinogen, chymotrypsinogen and lipase synthesis, and amylase secretion were measured for 2 hr. Results showed that, compared to controls, acini of rats with AP had increased amylase content, a finding consistent with decreasedin vivo amylase secretion. Total protein and individual enzyme synthesis rates were significantly lower in the acini of the rats with AP than in those of the controls. Negative feedback inhibition of enzyme synthesis due to the increased stores of intracellular enzymes may account for these findings. BPN reduced pancreatic edema in rats with acute pancreatitis (AP). Acinar amylase content of rats with AP treated with BPN was significantly lower than in acini of rats with AP. As amylase secretion was lower in the AP + BPN rats, the reduced acinar amylase content was probably solely due to the reduction in enzyme synthesis observed in the AP + BPN rats. The results suggest that BPN may have a moderating effect on the development of AP.This study was supported by a research grant from the South African Medical Research Council.     

Morphological and biochemical changes in the pancreas of copper-deficient rats

Two types of experimental chronic pancreatic damage were induced in rats by a copper-deficient diet containing D-penicillamine (DP rats) and by a similar diet without D-penicillamine (D rats). At 5-6 weeks after commencement of treatment, serum copper levels showed a significant decrease in both DP rats (1.5 +/- 0.9 micrograms/dl, M +/- SE) and D rats (18.8 +/- 1.4 micrograms/dl) compared with the findings in control rats (111.8 +/- 4.4 micrograms/dl). Histology revealed loss and atrophy of acinar cells in DP rats and mild vacuolar degeneration of acinar cells in D rats, whereas the islets of Langerhans were intact in both groups. The secretion of the exocrine pancreas showed a marked decrease in enzymes and protein output in DP and D rats compared with findings in the control rats. Our study confirmed the relationships between serum copper levels and morphological damage of pancreatic acinar cells or the reduction of enzyme secretion. On the other hand, the reductions in volume and bicarbonate output of pancreatic juice in DP rats and in D rats were detected, but no relationship was found between these reductions and the serum copper levels. The endocrine pancreatic function in DP rats showed a slight disturbance in intravenous glucose tolerance test. These results support the conclusion that copper-deficiency causes disturbances in enzyme-synthesis and selective destruction of acinar cells.     

Atrial natriuretic factor and exocrine pancreas: effects on the secretory process

Immunoreactive atrial natriuretic factor (ANF) has recently been identified in pancreatic acinar cells. The current study therefore, was, designed to ascertain whether the atrial peptide exercises any biological effects on the exocrine pancreas. When isolated rat pancreatic acinar cells were incubated with rat ANF (8-33), a concentration-dependent increase in cGMP synthesis was observed (EC50 about 5 X 10(-9) M) with the peak response occurring within 2.5 min of exposure of the cells to the peptide. ANF did not affect basal or secretagogue (carbachol +/- DbcAMP, CCK-OP, or forskolin)-induced amylase secretion from acinar cells, nor did it affect [3H]thymidine incorporation into DNA or [3H]leucine incorporation into trichloroacetic acid-precipitable protein. ANF was also infused intravenously (0.01-0.25 micrograms/min) in rabbits with cannulated pancreatic ducts, and the peptide stimulated a dose-dependent secretion of cGMP into pancreatic juice. ANF, by itself, did not affect protein or fluid secretion from rabbit pancreas; when co-infused with secretin (0.1 CU/min), which is not an acinar cell secretagogue in rabbits, ANF increased fluid secretion in one of three animals tested. The data suggest that acinar cells possess functional ANF receptors, whose activation results in both synthesis and secretion of cGMP. Intra-acinar cell cGMP is not involved in the enzyme secretory process. Secreted nucleotide is not co-released with digestive hydrolases, and does not, by itself, appear to have an intraluminal effect on fluid secretion. The mechanism by which acinar cells secrete cGMP into pancreatic juice as well as the biological significance of intracellular (acinar), and extracellular (intraluminal) cGMP remain to be elucidated.     

Changes of lysosomal enzymes in pancreatic juice following hepatectomy in rats]

To explore the changes in the exocrine pancreas and the possible stimulation by gut hormones of secretion of lysosomal enzyme into the pancreatic juice, we measured the caerulein-stimulated amylase output, the cathepsin B output into the pancreatic juice and the pancreatic tissue amylase and cathepsin B contents, as well as the distribution of cathepsin B in acinar cells in both the regenerating (4 days) and recovery (8 days) stages after about 70% hepatectomy in rats. The amylase output increased significantly after hepatectomy. Cathepsin B was secreted into the pancreatic juice after stimulation by caerulein in both the control and hepatectomized groups. Four days after hepatectomy, the cathepsin B output was significantly greater than that of the control group, and redistribution of cathepsin B in acinar cells was noted. These changes in cathepsin B disappeared in the recovery stage (8 days) after hepatectomy. In addition, the pancreatic amylase content was significantly higher than in the control group, but the pancreatic cathepsin B content did not change significantly. These results suggest that caerulein stimulated the secretion of lysosomal enzyme into the pancreatic juice in the same way as digestive enzymes and that lysosomal enzymes in the pancreatic juice play an important physiological role. Furthermore, these results indicate the increased synthesis and secretion of amylase in and from acinar cells as well as the fragility of acinar cells.     

The effect of chronic exercise on the rat pancreas.

BACKGROUND: We recently demonstrated that chronic physical exercise increases pancreatic protein content and basal amylase secretion. It is unknown whether chronic exercise causes hypertrophy or proliferation of pancreatic acinar cells. METHODS: Female F344 rats (age, 6 wk) were divided into control (n = 7) and exercise (n = 6) groups. Food consumption was matched between the 2 groups. Rats in the control group were kept sedentary. Rats in the exercise group were exercised for 60 min, 5 d/wk during the experiment. After 8 wk, the pancreas and hindlimb muscles were rapidly excised and weighed. Protein and DNA content and enzyme activity in pancreatic tissue were measured. Pancreatic tissues from control and exercised rats were also prepared for transmission electron microscopy. RESULTS: Inhibition of growth and hypertrophy of hindlimb muscles were exhibited by the exercise group. In the exercise group, pancreatic wet weight, protein content, and amylase and lipase activities, but not DNA content, were significantly higher than those in the control group. Electron micrographs clearly revealed that acinar cells were hypertrophied and zymogen granules were increased in number in exercised rats. CONCLUSION: Chronic endurance exercise increases pancreatic weight, protein content and enzyme activity through hypertrophy of acinar cells.