Protective effect of human pancreatic secretory trypsin inhibitor on cerulein-induced acute pancreatitis in rats.

We examined the protective effect of human pancreatic secretory trypsin inhibitor (PSTI), a specific trypsin inhibitor secreted from pancreatic acinar cells into the pancreatic duct, on cerulein-induced acute pancreatitis in conscious rats. The protective effect of human PSTI-RS, an analogue of PSTI with Arg-44 to Ser substitution which has a longer half-life in vitro, was also examined. Intraperitoneal administration of a pharmacological dose of cerulein to conscious rats induced acute pancreatitis, characterized by light microscopy as cellular disorganization of the acini and interstitial edema. Intravenous infusion of human PSTI (10, 50 or 250 micrograms/rat/h) into rats with cerulein-induced acute pancreatitis decreased their pancreatic wet weight and plasma amylase concentration. It also caused a dose-dependent decrease in vacuoles in acinar cells and interstitial edema. Human PSTI-RS, which has a longer half-life in vivo, was more effective than native PSTI at the same dose rate (10 micrograms/rat/h) in reducing pancreatitis. These results suggest that human PSTI may have a beneficial effect on acute pancreatitis.     

Pancreatic and bile duct obstruction exacerbates rat caerulein-induced pancreatitis: a new experimental model of acute hemorrhagic pancreatitis

Background Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein. Methods In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated. Results Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction. Conclusions Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.     

Acute necrotizing pancreatitis in the opossum: earliest morphological changes involve acinar cells.

Acute pancreatitis was induced by ligating the opossum common biliopancreatic duct immediately proximal to its entry into the duodenum, and macroscopic as well as microscopic changes were evaluated during the subsequent 24 hours. Transient pancreatic edema and progressive hyperamylasemia were noted within 6 hours of pancreatic and bile duct ligation. Light microscopic evidence of pancreatic injury including acinar cell necrosis, hemorrhage, fat necrosis, and inflammatory cell infiltration was noted within 12 hours of duct obstruction. Electron microscopic changes included massive dilatation of the rough endoplasmic reticulum and disruption of the apical plasmalemma of acinar cells during the initial 3 hours. These observations indicate that pancreatic and bile duct ligation in the opossum results in the rapid (less than 24 hours) appearance of changes consistent with acute hemorrhagic and necrotizing pancreatitis and that the initial lesion in this model of experimental pancreatitis involves acinar cells.     

Long-term evolution of acinar-to-ductal metaplasia and β-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model

BackgroundPancreatic duct ligation (PDL) has been used as a model of chronic pancreatitis and as a model to increase β-cell mass. However, studies in mice have demonstrated acinar regeneration after PDL, questioning the long-term validity of the model. We aim to elucidate whether RF-assisted transection (RFAT) of the main pancreatic duct is a reliable PDL model, both in short (ST, 1-month) and long-term (LT, 6-months) follow-ups.MethodsEleven pigs were subjected to RFAT. Biochemical (serum/peripancreatic amylase and glucose) and histological changes (including a semiautomatic morphometric study of over 1000 images/pancreas and IHC analysis) were evaluated after ST or LT follow-up and also in fresh pancreas specimens that were used as controls for 1 (n = 4) and 6 months (n = 6).ResultsThe distal pancreas in the ST was characterized by areas of acinar-to-ductal metaplasia (56%) which were significantly reduced at LT (21%) by fibrotic replacement and adipose tissue. The endocrine mass showed a normal increase.ConclusionRFAT in the pig seems to be an appropriate PDL model without restoration of pancreatic drainage or reduction of endocrine mass.     

Bile exclusion from the gut exacerbates acute pancreatitis caused by pancreatic duct obstruction in rats.

Acute pancreatic duct obstruction causes hyperamylasemia and mild pancreatic inflammation. We hypothesized that bile exclusion from the gut, which stimulates pancreatic secretion, exacerbates acute pancreatitis caused by pancreatic duct obstruction. Rats were surgically prepared with gastric, duodenal, bile, and pancreatic fistula catheters and a jugular vein catheter. After a 4-day recovery, groups of rats (a) served as controls, (b) had complete pancreatic duct obstruction for 6 h, or (c) had bile excluded from the gut for 24 h and then, during the final 6 h, complete pancreatic duct obstruction. Plasma amylase was measured, and all rats were euthanized at the end of experiments. Each pancreas was excised and weighed, and portions were fixed in formalin and glutaraldehyde. In blind fashion, each pancreas was examined under light microscopy and assigned a pancreatitis score based on presence of edema and severity of acinar cell changes and inflammation. Acute pancreatic duct obstruction was associated with increased pancreas weight, hyperamylasemia, and elevated pancreatitis score; moderate acinar cell vacuoles, which were observed in the cytoplasm near the basolateral membrane, and loss of microvilli were noted with electron microscopy. Bile exclusion from the gut exacerbated the acute pancreatitis caused by pancreatic duct obstruction; acinar cell distortion and destruction, as well as marked inflammation, were seen microscopically. These observations suggest that the absence of intestinal bile contributes to the pathogenesis of acute pancreatitis associated with pancreatic duct obstruction.     

Time course and cellular source of pancreatic regeneration following acute pancreatitis in the rat

The regenerative capacity of the different cell types in the rat exocrine pancreas has been studied in a model of hormone-induced acute pancreatitis in which pancreatic edema, inflammation, and acinar cell destruction were induced within 12 h of infusion of supramaximal concentrations of cerulein (5 micrograms/kg/h). A sequential biochemical and structural analysis of the pancreas in daily intervals was combined with the autoradiographic quantitation of labeling indices of five cell populations following 3H-thymidine injection at days 1-7 after induction of pancreatitis. Desquamation of acinar cell apical cytoplasm and release of cytoplasmic segments into the acinar lumen on the first day following induction of pancreatitis led to formation of duct-like tubular complexes. Enzyme content in the pancreas decreased progressively following the formation of the edema to levels 15-20% of controls and remained reduced during the initial 5 days. Thymidine incorporation into total DNA showed a biphasic pattern with a distinct peak at day 1 and a second broader peak between days 4 and 7. Autoradiographic quantitation of labeling indices demonstrated the exclusive incorporation into intercalated duct cells and interstitial cells during the initial 24 h, while the second peak was predominantly due to labeling of acinar cells. Larger interlobular ducts and islets did not show changes in labeling index. In vivo labeling with 3H-thymidine during the first day and analysis of labeling indices 14 days later showed the persistence of label in intercalated duct cells and interstitial cells and argued against the stem cell hypothesis and against transformation of duct cells into acinar cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of pancreatic secretion by vagal nerve during short-term duct occlusion in conscious rats

The basal exocrine secretion of the pancreas is maintained at a constant level in conscious rats. We examined the changes in basal secretion with respect to the effect of various time periods of pancreatic duct occlusion (PDL). Male Wistar rats were prepared with cannulae that separately drained bile and pancreatic juice as well as with a duodenal cannula. Rats were placed in restraint cages, and experiments were conducted without anesthesia 4 days after the operation. Cholecystokinin (CCK) release was artificially prevented by the continuous infusion of bile with trypsin into the duodenal lumen throughout the experimental period to avoid the modification of pancreatic response by CCK. After 2-h basal collection, a pancreatic secretion was interrupted for 0.5-4 h, and then the collection of pancreatic juice was initiated again for an additional 2-4.5 h. The pancreatic secretion after the reopening of the 0.5-to 3-h PDL was comparable to basal secretion levels. However, protein secretion was significantly inhibited after the removal of 4-h PDL. Both vagotomy and capsaicin treatment abolished this inhibition, and the protein secretion after 1-h PDL in vagotomized rats increased 1.5-fold high compared with the basal value. These observations indicate that protein secretion was ceased during PDL via vagal nerve, and this may be a self-protective mechanism.     

Expression of PGP9.5 in ductal cells of the rat pancreas during development and regeneration: can it be a marker for pancreatic progenitor cells?

The expression of protein gene product 9.5 (PGP9.5), a known neuron marker, was immunohistochemically investigated in rat pancreas. In fetal pancreas, a cluster of cells expressed PGP9.5 among the initial epithelial buds at embryonic day 11.5 (E 11.5). At E 13.5, PGP9.5 appeared among elongated and branching epithelial cells as well as along nerve fibers in the mesenchyme. On E 17.5, tubular cells became ductal cells with lumen, which strongly expressed PGP9.5. In newborn rats, ductal cells of the common bile duct (CBD) to the centroacinar cells and islet cells expressed PGP9.5. Ten days after birth, the number of the ductal cells expressing PGP9.5 was reduced, and PGP9.5-negative cells appeared in half of the duct cells. On day 21, all centroacinar cells and intercalated ductal cells became PGP9.5-negative, but some CBD and interlobular ductal cells remained positive for PGP9.5. On day 28 and thereafter, PGP9.5 was no longer detected. In a pancreatic duct ligation model, acinar cells changed to cells with duct-like structure after duct ligation. These cells strongly expressed PGP9.5 on the fifth day after duct ligation. Three to four weeks after ligation, the cells with duct-like structure changed to acinar cells, islets of Langerhans and ductal cells, but the ductal cells were PGP9.5-negative at this point. These results suggested that PGP9.5 is expressed in ductal cells that possess a potential for differentiation to pancreatic endocrine cells, and therefore can serve as a marker for the progenitor of pancreatic endocrine cells.     

CCK-A receptor induction and P38MAPK and NF-κB activation in acute pancreatitis

Bile-pancreatic duct ligation in rats excludes bile-pancreatic juice from the gut and induces acute pancreatitis. Bile-pancreatic juice exclusion from the gut results in increased plasma cholecystokinin (CCK) levels. CCK-A receptor-mediated exocrine pancreatic hyperstimulation is implicated in disease pathogenesis. In the present study, we show for the first time a progressive rise in CCK-A receptor protein expression in ligation-induced acute pancreatitis in rats. As CCK-A receptor induction could amplify CCK-mediated acinar hyperstimulation and exacerbate acinar cell stress with activation of the p38^MAPK stress kinase pathway, we studied CCK-A receptor protein expression and p38^MAPK activation in duct ligation-induced acute pancreatitis in rats. Compared to sham-operated controls, acute pancreatitis induced by bile-pancreatic duct ligation associates with a temporal increase in pancreatic CCK-A receptor protein expression, p38^MAPK expression and activation, and NF-κB activation. These findings may have significance in the mechanism of disease pathogenesis in this experimental model.     

Mechanism of increased exocrine pancreatic secretion in pancreatic juice-diverted rats

We investigated a possible role of endogenous cholecystokinin-pancreozymin (CCK-PZ) in the mechanism of exocrine pancreatic secretion after excluding pancreatic juice from the intestine in rats. Fasting plasma immunoreactive CCK-PZ was determined in normal rats, in rats with pancreatic duct ligation, and in sham-operated rats. The mean fasting plasma CCK-PZ concentration of rats with pancreatic duct ligation, 25.1 +/- 2.0 pM, was significantly greater (p less than 0.001) than those of normal and sham-operated rats, 14.3 +/- 1.7 and 11.5 +/- 2.2 pM, respectively. Whereas mean postprandial plasma CCK-PZ concentrations of normal and sham-operated rats were significantly greater (p less than 0.001) than their fasting levels, no significant increase occurred in the rats with pancreatic duct ligation after a meal. The mean fasting plasma CCK-PZ concentration of rats with pancreatic duct ligation was comparable to the mean postprandial CCK-PZ level of normal and sham-operated rats. To determine a possible role of circulating endogenous CCK-PZ on the pancreatic secretion, anesthetized rats were prepared with ligation of pylorus and cannulation of pancreatic duct. After diversion of pancreatic juice began, pancreatic secretion including protein significantly increased, which coincided with a significant increase in plasma CCK-PZ concentration. The increases in both pancreatic secretion and plasma CCK-PZ were reversed by intraduodenal administration of bovine trypsin or rat pancreatic juice. Furthermore, the increase in pancreatic secretion was abolished by intravenous infusion of proglumide or an intravenous bolus injection of a rabbit anti-CCK-PZ serum, which also blocked clearly the increase in the pancreatic secretion stimulated by exogenous CCK-PZ8 (0.125 micrograms X kg-1 X h-1) in rats. Thus we conclude that the increase in pancreatic secretion resulting from elimination of pancreatic juice from the intestine is attributable, in part, to increased release of CCK-PZ, and thus it is suggested that trypsin in the intestinal lumen plays a significant role in release of CCK-PZ.     

The role of phospholipase A2 in pancreatic acinar cell injury

The integrity of rat pancreatic acinar cells under the influence of human phospholipase A2 (PLA2) was studied. Isolated pancreatic acini showed no increased discharge of aspartylaminotransferase (ASAT) when incubated either in solutions containing human pancreatic PLA2 or the bile salt sodium deoxycholate (DEC), the latter in concentrations that augment PLA2 activity but have no destructive detergent effect. When human pancreatic PLA2 was injected into the rat pancreatic duct, uneven distribution was observed at 15 min and 3 h in immunohistochemical sections. Edema and a mild inflammatory reaction were the main changes in the pancreas. The necrotic areas seen by light and electron microscopy were quite small and located mostly at the periphery of lobules corresponding the spread of the injected material. Necrosis was of the coagulation type and showed equal extent after the injection of PLA2 with or without DEC. Internalized human pancreatic PLA2 was present already 15 min after the injection in the cytoplasm of some intact acinar cells, indicating a functioning protective mechanism. It was concluded that pancreatic acinar cells are quite resistant to PLA2-catalyzed hydrolysis of membrane phospholipids in vitro, but additional trauma, e.g., pressure caused by intraductal injection, and tissue related factors, such as the mediators of the inflammatory reaction, make acinar cells susceptible to the effect of PLA2.     

共聚焦激光内镜观察急性胰腺炎微循环的实验研究

目的 探讨共聚焦激光内镜(CLE)在活体观察急性胰腺炎(AP)微循环变化的价值.方法 将32只SD大鼠随机分为:对照组8只,进腹后仅做相应的翻动,找出胃、十二指肠、胰腺后,充分暴露胰腺,找到下腔静脉采血后按照4 ml/kg注射0.5%荧光素钠,注射完毕时以CLE观察胰腺组织并记录;实验组24只,进腹结扎胆总管末端制作AP模型,分别在AP模型制作完成后12 h(12 h组,8只)、24 h(24 h组,8只)、48 h(48 h组,8只)再次开腹观察胰腺,找到下腔静脉采血后注射荧光素钠,注射完毕时以CLE观察病变胰腺组织并记录.各组均取胰腺组织做病理切片.结果 运用CLE可以观察到正常胰腺腺泡结构和毛细血管以及血管中流动的红细胞,并有可能数出一时段内通过某一毛细血管横切面的红细胞个数;12 h组腺泡结构基本正常,微循环毛细血管内可见红细胞流动但流速明显减慢;24 h组部分腺泡结构显影模糊,但仍可见结构基本正常的腺泡,能够观察到的微循环毛细血管明显减少,毛细血管内红细胞数量明显减少且流速很慢;48 h组腺泡显影模糊,部分腺泡不显影,几乎观察不到正常腺泡结构,极少能够观察到微循环毛细血管,且血管内罕见红细胞,几乎无红细胞流动.CLE未能观察到确切的胰岛组织,难以辨识白细胞,不能判断是否有微血栓形成.结论 CLE对胰腺微循环研究有较大价值,特别是对活体AP微循环血流状态的判断较以往实验方法具明显优势,但仍需要改进显色剂和图像处理技术以获得更易辨识的图像,提升其应用价值.     

糖皮质激素对急性胰腺炎大鼠胰腺细胞凋亡的影响及其意义

目的　探讨糖皮质激素对急性胰腺炎 (AP)大鼠胰腺细胞凋亡的影响及其意义。方法　将SD大鼠 5 4只随机分为 3组 :正常对照组 ,胰腺炎组和激素治疗组 ,每组 18只。经十二指肠行胆胰管逆行加压注射 4 %的牛磺胆酸钠 ,诱导大鼠 AP模型 ,于术后 3h、6 h和 12 h采取断颈方法分批处死动物 ,应用末端脱氧核苷酸转换酶 (Td T)介导的原位末端标记 (TUNEL )法检测胰腺组织细胞凋亡变化 ,观察各组大鼠胰腺组织病理改变。结果　 (1) AP大鼠的胰腺凋亡细胞增多 ,与对照组比较均有显著差异 (P<0 .0 1) ,注射激素后 ,胰腺凋亡细胞减少 ,6 h、12 h的凋亡指数均显著低于对应时相的 AP组 (P<0 .0 5 ) ;(2 )激素治疗后 ,AP大鼠胰腺炎症细胞、坏死细胞明显减少 ,病变减轻 ,6 h、12 h病理评分均显著低于 AP组 (P<0 .0 5 )。结论　糖皮质激素具有抑制胰腺细胞凋亡的作用 ,保护腺泡细胞、阻止细胞死亡可能是糖皮质激素减轻 AP病变严重程度的一个重要因素。     

Intervention of pyrrolidine dithiocarbamate and tetrandrine on cellular calcium overload of pancreatic acinar cells induced by serum and ascitic fluid from rats with acute pancreatitis

Background and Aim:  To investigate the effects of serum and ascitic fluid from rats with acute pancreatitis (AP) on cellular free calcium concentration ([Ca²⁺]i) of isolated rat pancreatic acinar cells, and the intervention of pyrrolidine dithiocarbamate (PDTC) and tetrandrine (Tet) to cellular calcium overload in AP.
Methods:  AP was induced in Sprague–Dawley rats with a retrograde pancreatic duct injection of 3% sodium deoxycholate, and confirmed by histopathological examination and amylase activity assay. The rat serum and ascitic fluid were collected at 1, 5 and 10 h after AP induction, and used as irritants on isolated rat pancreatic acinar cells. The effects on intracellular [Ca²⁺]i, and cell viability were examined. Then, the antagonistic effects of different concentrations of PDTC and Tet were assessed.
Results:  The irritation with AP serum and ascitic fluid reduced the survival rate of the isolated rat pancreatic acinar cells and increased the cellular [Ca²⁺]i significantly ( P  < 0.05). As AP induction course prolonged, the stimulation effect of the AP serum and ascitic fluid intensified. In the pretreated acinar cells with PDTC or Tet, the decreased cell vitality reverted. The elevation of [Ca²⁺]i in the acinar cells significantly ameliorated (significant, P  < 0.05; very significant, P  < 0.01).
Conclusion:  The serum and ascitic fluid from AP rats drastically elevate the [Ca²⁺]i in isolated pancreatic acinar cells and decrease cell vitality, while the pretreatment of cells with PDTC and Tet offsets the calcium overload irritated by the AP serum and ascitic fluid and protects these isolated acinar cells.     

Distribution, release, and secretory activity of epidermal growth factor in the pancreas.

This study was designed to determine the distribution of immunoreactive epidermal growth factor (EGF) in the gastrointestinal tract and the action of this peptide on pancreatic secretion in vivo and in vitro. Immunoreactive EGF was found in large amounts in the salivary glands and the pancreas and in the pancreatic juice. EGF infused subcutaneously (50 micrograms/kg-h) in conscious rats with intact or removed salivary glands stimulated pancreatic protein secretion after 4 h of peptide infusion; this effect was completely prevented by the pretreatment with DL-difluoromethyl-ornithine (DFMO) (200 mg/kg), an irreversible inhibitor of activity of ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis. EGF added to the incubation medium in concentrations ranging from 10(-10)-10(-6) M increased, in a concentration-dependent manner both unstimulated and stimulated by caeruelin or urecholine, amylase release from dispersed pancreatic acini obtained from rats pretreated in 3 h with EGF in a dose of 50 micrograms/kg-h. Spermine given at concentrations ranging from 10(-12)-10(-6) M to the freshly prepared rat pancreatic acini also increased amylase release in a concentration-related manner. DFMO injected in a single dose (200 mg/kg), before the infusion of EGF to the rats, completely abolished the stimulatory effect of EGF on amylase release, but failed to affect that of spermine. This study shows that 1. EGF is present in large amounts in pancreatic tissue and pancreatic juice. 2. EGF stimulates pancreatic secretion in vivo and amylase release in vitro from isolated rat pancreatic acini. 3. The activation of ODC and polyamine biosynthesis in acinar cells plays an important role in EGF-induced stimulation of pancreatic secretion.     

The role of phospholipase a2 in pancreatic acinar cell injury

The integrity of rat pancreatic acinar cells under the influence of human phospholipase A₂ (PLA2) was studied. Isolated pancreatic acini showed no increased discharge of aspartylaminotransferase (ASAT) when incubated either in solutions containing human pancreatic PLA₂ or the bile salt sodium deoxycholate (DEC), the latter in concentrations that augment PLA₂ activity but have no destructive detergent effect. When human pancreatic PLA₂ was injected into the rat pancreatic duct, uneven distribution was observed at 15 min and 3 h in immunohistochemical sections. Edema and a mild inflammatory reaction were the main changes in the pancreas. The necrotic areas seen by light and electron microscopy were quite small and located mostly at the periphery of lobules corresponding the spread of the injected material. Necrosis was of the coagulation type and showed equal extent after the injection of PLA₂ with or without DEC. Internalized human pancreatic PLA₂ was present already 15 min after the injection in the cytoplasm of some intact acinar cells, indicating a functioning protective mechanism. It was concluded that pancreatic acinar cells are quite resistant to PLA₂-catalyzed hydrolysis of membrane phospholipids in vitro, but additional trauma, e.g., pressure caused by intraductal injection, and tissue related factors, such as the mediators of the inflammatory reaction, make acinar cells susceptible to the effect of PLA₂.     

The effects of verapamil in experimental acute pancreatitis in the rat]

Experimental studies have shown that verapamil inhibits pancreatic exocrine secretion. In order to determine whether verapamil has any effect on acute pancreatitis (AP), we undertook an experimental study in Wistar rats. We used 72 animals divided into two groups. In all animals of both experimental groups, AP was induced by ligation of the biliary duct at its entrance in the duodenum. Animals were given saline (NaCl 0.9%), or 0.30 mgrs/hour verapamil. Subgroups of 9 animals, were treated for 6, 12, 18 and 24 hours; 6 animals group were then sacrificed, for biochemical studies (serum amilase, lipase, and calcium; and trypsin and chemotrypsin in the homogenized pancreas); the other 3 animals were used for morphologic study of the pancreas. Verapamil treatment decreased significantly tissue activity of trypsin (p less than 0.001) and chemotrypsin (p less than 0.0001) and increased serum lipase (p less than 0.05), and calcium. There was no statistical difference in serum amylase. Morphological findings include oedema, acinar necrosis, hemorrhage and vasculitis in non treated animals. Only oedema was observed in animals treated with verapamil. These results suggest a beneficial effect of verapamil on experimental AP induced by ligation of the bile duct in the rat.     

Pancreatic regenerating protein (reg I) and reg I receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis

AIM: Pancreatic regenerating protein (reg Ⅰ) stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and β-cells. This suggests that reg Ⅰ and its receptor may play a role in recovery after pancreatic injury. We hypothesized that reg Ⅰ and its receptor are induced in acute pancreatitis.METHODS: Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls (4 rats/group). Reg Ⅰ receptor mRNA, serum reg Ⅰ protein, and tissue reg Ⅰ protein levels were determined by Northern analysis, enzymelinked immunosorbent assay (ELISA), and Western analysis, respectively. Immunohistochemistry was used to localize changes in reg Ⅰ and its receptor.RESULTS: Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum reg Ⅰ concentrations from controls. However,Western blot demonstrated increased tissue levels of reg Ⅰ at 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in reg Ⅰ receptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells.CONCLUSION: Acute pancreatitis results in increased tissue reg Ⅰ protein levels localized to the acinar and ductal cells, and a parallel threefold induction of reg Ⅰ receptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg Ⅰ and its receptor may be important for recovery from acute pancreatitis.     

Pancreatic regenerating protein (reg Ⅰ) and reg Ⅰ receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis

AIM: Pancreatic regenerating protein (reg Ⅰ) stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and β-cells. This suggests that reg Ⅰ and its receptor may play a role in recovery after pancreatic injury. We hypothesized that reg Ⅰ and its receptor are induced in acute pancreatitis.METHODS: Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls (4 rats/group). Reg Ⅰ receptor mRNA, serum reg Ⅰ protein, and tissue reg Ⅰ protein levels were determined by Northern analysis, enzymelinked immunosorbent assay (ELISA), and Western analysis, respectively. Immunohistochemistry was used to localize changes in reg Ⅰ and its receptor.RESULTS: Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum reg Ⅰ concentrations from controls. However,Western blot demonstrated increased tissue levels of reg Ⅰ at 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in reg Ⅰ receptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells.CONCLUSION: Acute pancreatitis results in increased tissue reg Ⅰ protein levels localized to the acinar and ductal cells, and a parallel threefold induction of reg Ⅰ receptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg Ⅰ and its receptor may be important for recovery from acute pancreatitis.     

Acute pancreatitis： Etiology and common pathogenesis

Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux.Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.