Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

ABM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ(PPARγ) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas. METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined, Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS: Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the over-expression of HSP70. PPARγ ligands could represent a new therapeutic option in the treatment of AP.     

Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas.METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined.Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein.RESULTS: Pioglitazone administered (10-100 mg/kg I.g.)30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity,plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment.CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70.PPARγ ligands could represent a new therapeutic option in the treatment of AP.     

Pancreatic exocrine function during acute exacerbation in WBN/Kob rats with spontaneous chronic pancreatitis

Summary Conclusion Pancreatic exocrine hypofunction is markedly deteriorated during acute exacerbation in a rat model with chronic pancreatitis. Background Little is known about pancreatic exocrine function during acute exacerbation in patients with chronic pancreatitis. We investigated changes in pancreatic exocrine function after inducing acute pancreatitis in an animal model of spontaneous chronic pancreatitis. Methods WBN/Kob rats with chronic pancreatitis sequentially underwent pancreatic exocrine function test 1–6 d after surgical preparation with external pancreatic fistula. We induced acute pancreatitis in another WBN/Kob rats by iv administration of cerulein at a rate of 10 μg/kg/h for 4 h 4 after surgical preparation. Pancreatic exocrine function test was undertaken in a conscious state 1 d before and after cerulein administration. Results In WBN/Kob rats not given cerulein, pancreatic exocrine function remained almost constant, at 3–6 d after surgery. Marked hyperamylasemia developed immediately after cerulein administration. After its administration, the pancreas microscopcially showed prominent intersitial edema and intracellular vacuolization of acinar cells in addition to the finding of pre-existing chronic pancreatitis. Basal and chole-cystokinin-stimulated flow rate, bicarbonate output, and protein output, which were substantially impaired 1 d before cerulein administration, were further reduced 1 d after its administration.     

Oxygen-derived free radicals in cerulein-induced acute pancreatitis

Conscious rats were treated with a supramaximal dose of 5.10(-6)g.kg-1.h-1 of cerulein for periods of 3 and 12 h. In both groups of animals typical features of acute oedematous pancreatitis were proved by biochemical and histologic examinations. The most important finding of our study was the decrease of superoxide dismutase (SOD) activity in pancreatic tissue, accompanied by a slight increase of this scavenger enzyme in serum of rats stimulated with cerulein during 3 h. Parallelly, evident elevation of malondialdehyde (MDA) concentration in pancreatic tissue was noted. After the 12-h infusion of cerulein we were not able to detect any SOD activity in pancreatic tissue, whereas this activity appeared in ascitic fluid of tested animals. Further increase of MDA concentration in pancreatic tissue, in comparison with 3-h pancreatitis, was found. These data suggest that in 3-h and 12-h cerulein-induced pancreatitis the oxygen-derived free radicals mediate the increased lipid peroxidation in pancreatic tissue. We think that the depletion of the scavenger enzyme SOD may be responsible for such a disturbance of lipid metabolism.     

Does stress play a role in the development of severe pancreatitis in rats?

The purpose of this study was to investigate whether stress plays a role, morphologically and enzymatically, in the development of severe pancreatitis in rats. Acute hemorrhagic pancreatitis was induced by two intraperitoneal injections of cerulein (40 micrograms/kg body wt) at intervals of 1 h under water-immersion stress for 5 h, whereas water-immersion stress alone did not induce any morphologic and enzymatic changes in the pancreas. In this model, hemorrhagic pancreatitis developed continuously, and the serum amylase level and activation of zymogen proteases in pancreatic tissue were significantly higher than in cerulein-induced pancreatic tissue 5 h after the first cerulein injection. Furthermore, the effects of cerulein on the serum amylase level and activation of zymogen proteases were dose related. Even 5 micrograms/kg body wt of cerulein, which did not induce any evident edematous change in the pancreas, could activate the zymogen proteases of pancreatic tissue fairly well under water-immersion stress compared with pancreatitis induced by 40 micrograms/kg body wt of cerulein alone. These results indicate that stress accelerates the activation of zymogen proteases induced by cerulein and suggest the possibility that stress may play some role in the development of severe pancreatitis.     

Manifestations of experimental acute pancreatitis in young and old rats

Two kinds of experimental pancreatitis were induced in young (4-6 month) and old (25-27 month) female Wistar rats: acute edematous pancreatitis was induced by intraperitoneal administration of a high dose of cerulein (40 micro/kg x 2) and acute hemorrhagic pancreatitis was intraductal injection of 1% deoxycholic acid. After these treatments, the plasma amylase concentration and pancreatic wet weight were determined and the pancreas was examined histologically. In the groups with cerulein induced pancreatitis one of eight old rats died, whereas all five young rats survived. There was no specific finding macroscopically in the liver, kidney, lung or heart of old rats at autopsy after cerulein injection. The plasma amylase concentration and the pancreatic wet weight were significantly increased by administration of cerulein or deoxycholic acid in both young and old rats. There was no significant difference in the plasma amylase concentrations in young and old rats after the induction of acute pancreatitis. The increase in pancreatic wet weight was less in old rats than in young ones after deoxycholic acid treatment, but similar in the two groups after cerulein injection. The extents of histological changes were also similar in young and old rats. Thus, no evidence that aging increases susceptibility to pancreatitis was obtained.     

Oxygen radicals mediate depletion of pancreatic sulfhydryl compounds in rats with cerulein-induced acute pancreatitis

Acute edematous pancreatitis was induced in conscious rats by intravenous infusion of cerulein at a supramaximal dose of 7.5 micrograms/kg/h during 6 h. The most important finding of our study was a marked decrease in the protein and non-protein content of sulfhydryl groups parallel to an evident elevation in the malondialdehyde concentration in pancreatic tissue. The presented data suggest that in cerulein-induced acute pancreatitis in rats, oxygen radicals mediate increased peroxidation reactions which are accompanied by depletion of nonenzymatic sulfhydryl-containing free radical scavengers. The above phenomenon contributes to a disturbance in thiol metabolism resulting in serious diminution of pancreatic protein sulfhydryl compounds.     

Soybean trypsin inhibitor and cerulein accelerate recovery of cerulein-induced pancreatitis in rats.

The role of exogenous and endogenous cholecystokinin has been studied in the process of pancreatic regeneration after acute pancreatitis. A mild form of pancreatitis was induced in rats by subcutaneous cerulein at 12 micrograms.kg-1, three times a day for 2 days. After 3 days of rest, the cerulein-treated rats were divided into four groups: rats with acute pancreatitis fed 20% casein, who received no treatment; rats fed 50% casein; rats fed 20% casein supplemented with 1% soybean trypsin inhibitor (SBTI); and rats fed 20% casein who received 1 microgram.kg-1 of subcutaneous cerulein, three times a day. Controls were fed 20% casein plus saline subcutaneously. Rats were killed after 5, 10, or 20 days of treatment. Pancreatitis resulted in significant decreases in pancreatic weight and contents of protein, amylase, chymotrypsin, RNA and DNA. During the regenerative process, 1 microgram.kg-1 of cerulein increased all parameters to control values within 5 days and induced pancreatic growth thereafter. SBTI restored the pancreas to normal after 10 days with cellular hypertrophy; the 50% casein diet gave a response similar to SBTI without hypertrophy. It can be concluded that cerulein and SBTI can accelerate pancreatic regeneration after an attack of acute pancreatitis.     

C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and in pancreatic cancer cells

BACKGROUND: Activation of the receptor c-met stimulates motility, mitosis, morphogenesis, processes involved in organ regeneration, or progression of malignancies. In the present study we investigated the expression of c-met protein in the regenerating pancreas and characterized the influence of cytokines on c-met expression. METHODS: Acute pancreatitis was induced in rats by cerulein injection. Rat acini and rat and human pancreatic cancer cells were stimulated with interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta1 (TGF-beta1). C-met expression was analyzed by means of Western blotting and localization in pancreatic tissue by immunohistochemistry. RESULTS: C-met protein expression was significantly upregulated in the regenerating pancreas and localized in areas of regenerating tissue. Stimulation with cytokines resulted in a two- to threefold increase of c-met expression in vitro. CONCLUSION: Enhanced c-met expression after acute pancreatitis suggests that HGF/met has an important role in pancreatic regeneration, which is probably mediated by cytokines. This regulatory mechanism is also of importance in pancreatic cancer.     

The protective effect of the trypsin inhibitor urinastatin on cerulein-induced acute pancreatitis in rats

We examined the protective effects of the trypsin inhibitor, urinastatin, extracted from human urine in experimental acute pancreatitis in conscious rats. Acute pancreatitis was induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Urinastatin at a dose of 50,000 U/kg body weight/6.5 h was given by continuous i.v. infusion beginning 0.5 h before the first cerulein injection and continuing until 3 h after the last one, for a total of 6.5 h. Urinastatin significantly reduced serum levels of amylase, lipase, and anionic trypsin(ogen) but did not affect pancreatic wet weight or protein or enzyme content. Urinastatin also significantly reduced the degree of acinar cell vacuolization, interstitial edema, and cellular infiltration. These results suggest that urinastatin does not block the induction of acute pancreatitis by cerulein but does substantially reduce its severity.     

Cholecystokinin antagonist prevents hyperamylasemia and improves pancreatic exocrine function in cerulein-induced acute pancreatitis.

Supramaximal cerulein administration induces acute pancreatitis, which markedly impairs pancreatic secretion in conscious rats. We hypothesized that pretreatment with the potent cholecystokinin antagonist, L-364,718, improves the pancreatic secretory impairment associated with cerulein-induced acute pancreatitis. Rats were surgically prepared with gastric, duodenal, bile, and pancreatic fistulas and jugular vein catheters. On postoperative day 4, groups of rats were administered (a) L-364,718 1 mg/kg intraduodenally, (b) cerulein 5 micrograms/kg/h for 6 h intravenously, (c) L-364,718 1 mg/kg intraduodenally followed by cerulein 5 micrograms/kg/h for 6 h intravenously, and (d) safflower oil carrier intraduodenally. On postoperative day 5, we studied cholecystokinin (CCK)-stimulated pancreatic secretion. Plasma amylase was measured at the time of surgery and at the conclusion of experiments on postoperative days 4 and 5. The duodenally administered CCK antagonist had no effect, 24 h later, on CCK-evoked protein secretion and prevented the pancreatic exocrine impairment and hyperamylasemia caused by supramaximal cerulein administration. These observations suggest that cerulein-induced acute pancreatitis is mediated by a CCK-receptor mechanism.     

Protective effect of 4-hydroxy-TEMPO, a low molecular weight superoxide dismutase mimic, on free radical toxicity in experimental pancreatitis

Summary Rats develop acute pancreatitis when infused iv for 3 h with cerulein (10 μg/kg/h). Autopsies of the pancreas seen by light microscope show interstitial edema, acinar cells vacuolization, and leukocyte margination in pancreatic capillaries; under electron microscope, severe damage concerning mitochondrial and zymogen granules structures are apparent. Particularly, swelling of the mitochondria and disruption of mitochondrial cristae was observed as well as formation of large vacuoles arising from zymogen granules and liposome fusion. A significant increase of lipid hydroperoxide level in the pancreatic tissue was observed. The purpose of this study was to evaluate the effect of 4-hydroxy-TEMPO—a low-mol-wt superoxide dismutase mimic—in a rat cerulein model of acute pancreatitis, with the expectation that free radical mediated hydroperoxide formation and tissue damage may be reduced significantly. Twenty-one male Wistar rats were divided into three groups: Group 1 (n=5) served as a control and was infused iv for 3 h with physiologic saline; Group 2 (n=8) was infused iv for 3 h with cerulein 10 μg/kg/h; and Group 3 (n=8) infused iv both with cerulein and 4-hydroxy-TEMPO 22.6 mg/kg/h. Pancreatic tissue damage was quantified by measuring lipid hydroperoxide (LOOH) level, the weight of the organ, and by light and electron microscopic examination. 4-hydroxy-TEMPO penetration across cellular membrane barriers was quantified by ESR spectrometric measuremts of 4-hydroxy-TEMPO concentration in pancreatic tissue samples and pancreatic juice as well. Administering 4-hydroxy-TEMPO to rats resulted in preventing both lipid hydroperoxide formation and severe morphological damage. 4-hydroxy-TEMPO crossed cellular membrane barriers and was excreted to pancreatic juice. Infusion of 4-hydroxy-TEMPO appears to prevent pancreatic injury caused by free radicals in experimental cerulein pancreatitis.     

Effects of octreotide in acute hemorrhagic necrotizing pancreatitis in rats

BACKGROUND AND AIM: Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest. METHOD: Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined. RESULTS: Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation. CONCLUSION: Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.     

组织因子、Egr-1及Sp1在大鼠狭窄颈动脉内皮细胞的表达

目的研究在体动物颈动脉狭窄处内皮细胞组织因子基因的切应力性表达规律及其机制。方法实验分为对照组和颈动脉狭窄组,套扎法建立左颈总动脉狭窄模型,狭窄组又分为0.5 h1、h3、h6、h、12 h1、d、3 d和7 d8个时间点,术后不同时间点用原位杂交和免疫组织化学法,检测组织因子、Egr-1和Sp1的mRNA和蛋白表达,用图像分析系统测定内膜平均灰度,进行统计学分析。结果对照组内皮细胞组织因子、Egr-1及Sp1的mRNA转录和蛋白合成弱;狭窄30 min后,与对照组比较内皮细胞胞质组织因子基因mRNA转录和蛋白合成升高(P<0.05),内皮细胞胞核和胞质Egr-1和Sp1基因mRNA转录和蛋白合成均增加(P<0.05),但以Egr-1增加更显著(P<0.05),其变化趋势与组织因子基因mRNA转录及蛋白合成的变化趋势相同。组织因子基因mRNA转录和蛋白合成于6 h达到峰值,Egr-1基因mRNA转录和蛋白合成于3 h达到峰值,Sp1基因mRNA转录和蛋白合成于1 h达到峰值,与对照组比较差异有显著性(P<0.05)。结论颈动脉狭窄时,切应力能够诱导动脉狭窄处内皮细胞组织因子基因表达,其表达与内皮细胞转录因子Egr-1和Sp1介导有关。     

Peptide Leukotriene Receptor Antagonist Diminishes Pancreatic Edema Formation in Rats with Cerulein-Induced Acute Pancreatitis

Background: This study was designed to evaluate the protective effect of a peptide leukotriene receptor antagonist, pranlukast hydrate, against pancreatic injuries during acute pancreatitis. Methods: Acute pancreatitis was induced in rats by intravenous infusion of a supramaximal dose of cerulein (5 μg/kg·h for 4 h). In this model marked hyperamylasemia, a significant increase in pancreatic water content, and a significant increase in pancreatic microvascular leakage of Evans blue dye were observed. Pancreatic subcellular redistribution of the lysosomal enzyme cathepsin B from the lysosomal fraction to the zymogen fraction was also observed. Results: Pretreatment with pranlukast hydrate at a dose of 10 mg/kg (twice, 8 and 4 h before cerulein infusion) significantly inhibited these pancreatic injuries, including hyperamylasemia, increased pancreatic microvascular permeability, and redistribution of cathepsin B in pancreatic acinar cells. Conclusions: These results suggest that peptide leukotrienes may be involved in the pathogenesis of acute pancreatitis in the early stage of the disease and that peptide leukotriene receptor antagonist might be of therapeutic value for treatment of acute pancreatitis.     

Involvement of endogenous cholecystokinin in pancreatic regeneration after cerulein-induced acute pancreatitis.

This study was undertaken to determine the involvement of endogenous cholecystokinin (CCK) in the regeneration of pancreatic tissue after cerulein-induced acute pancreatitis treated by the CCK receptor antagonist L364,718. Acute pancreatitis was induced in rats by s.c. injections of cerulein in gelatin (12 micrograms/kg) three times a day for 2 days with controls receiving saline in gelatin. Rats were then divided into four treatment groups: saline-dimethyl sulfoxide (DMSO) (SD), saline-L364,718 (SA), cerulein-pancreatitis-DMSO (CD), and cerulein-pancreatitis-L364,718 (CA). In the first experiment, rats were treated for 3 or 10 days with DMSO or L364,718 (0.1 mg/kg, twice a day). In the second experiment, rats were treated for 13 days with DMSO or L364,718 (1.0 mg/kg, twice a day). After the rats were killed, pancreata were weighed and evaluated for their total protein, amylase, chymotrypsin, RNA, and DNA. We found that destruction of the pancreatic tissue occurred after cerulein-induced pancreatitis and that regeneration of the tissue was in progress but incomplete after 10 days; the low dose of L364,718 did not prevent regeneration. After 13 days, regeneration was still incomplete but the 1-mg dose of L364,718 strongly inhibited spontaneous regeneration. These data suggest that endogenous CCK is an important and potent trophic factor in the regeneration process of pancreatic tissue following an episode of acute pancreatitis.     

A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice

BACKGROUND & AIMS: Cystic fibrosis transmembrane regulator (CFTR) gene mutations are associated with pancreatic insufficiency and pancreatitis. Chronic pancreatitis, including cystic fibrosis-related disease, may exist as a continuum between acute and chronic disease and may manifest as recurrent pain. We hypothesized that cftr(m1UNC) (-/-) mice, which have no evidence of chronic pancreatitis, are susceptible to developing acute pancreatitis. METHODS: We used a cerulein hyperstimulation model of acute pancreatitis and measured histological changes, tissue edema, neutrophil infiltration, inflammatory mediators' mRNA expression, apoptosis markers, and pancreatic trypsin and serum lipase activities. Additionally, we quantitated in vivo pancreatic secretion and pancreatic digestive enzymes. RESULTS: Multiple proinflammatory cytokine genes were constitutively overexpressed in cftr (-/-) pancreas compared with wild-type mice. During acute pancreatitis, cftr (-/-) mice developed more severe acute pancreatitis than wild-type, as indicated by greater pancreatic edema, neutrophil infiltration, mRNA expression of multiple inflammatory mediators, and less apoptotic cell death. In contrast to wild-type mice, cftr (-/-) mice had blunted increases in pancreatic trypsin and serum lipase activities, but similar percentages of pancreatic trypsinogen activation. Finally, cftr (-/-) mice had less in vivo pancreatic secretion in response to cholecystokinin octapeptide and reduced pancreatic digestive enzyme protein and mRNA levels, thus suggesting mild pancreatic insufficiency. CONCLUSIONS: A baseline proinflammatory state and an antiapoptotic phenotype may sensitize cftr (-/-) mice to developing more severe acute pancreatitis with an exuberant pancreatic inflammatory response. Cftr (-/-) mice have mild pancreatic insufficiency, which partially explains the blunted increase of pancreatic and serum digestive enzymes during acute pancreatitis. These findings may explain the susceptibility to acute pancreatitis in persons with classic and nonclassic cystic fibrosis.     

PIAS1基因沉默对胰腺腺泡细胞炎症反应的影响

目的 观察活化信号转导和转录激活因子的蛋白抑制因子-1(PIAS1)基因特异性siRNA干扰大鼠胰腺腺泡细胞株AR42J后对雨蛙素诱导炎症反应的影响,探讨其在胰腺炎发病中的作用.方法 采用脂质体法将靶向PIAS1的siRNA和阴性siRNA转染AR42J细胞,24 h后分别加入雨蛙素继续培养24 h.同时设脂质体+雨蛙素组、雨蛙素组及仅加PBS的对照组.Western blotting检测p38丝裂原激活蛋白激酶(p38MAPK)及磷酸化p38MAPK(P-p38MAPK)表达;RT-PCR及Western blotting检测各组细胞肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、IL-6、基质金属蛋白酶9(MMP-9)的mRNA和蛋白表达.结果 siRNA+雨蛙素组、阴性siRNA+雨蛙素组、脂质体+雨蛙素组、雨蛙素组及对照组细胞p38MAPK表达量分别为1.93±0.11、1.22±0.10、1.30±0.17、1.32±0.21、0.12±0.02;P-p38MAPK表达量分别为2.10±0.25、1.36±0.20、1.26±0.15、1.23±0.25、0.58±0.48,siRNA+雨蛙素组较其余各组明显增加(P值均＜0.05).siRNA+雨蛙素组细胞TNF-α、IL-1β、IL-6、MMP-9 mRNA表达量分别为1.66±0.15、1.66±0.15、1.90±0.01、1.56±0.20;蛋白的表达量分别为2.06±0.37、2.20±0.34、1.80±0.10、1.17±0.05,均较其他雨蛙素处理组表达上调(P值均＜0.05).结论 PIAS1参与雨蛙素诱导的胰腺腺泡细胞p38MAPK活性与下游炎症介质的表达调控.