Objective To investigate the changes of extraceUular regulated kinase 1/2 (ERK1/2) phosphorylation and assess the effects of blocking the ERK1/2 phosphorylation on rats with acute necrotizing pancreatitis (ANP). Methods The ANP model was induced by retrograde injection of 5% sodium tanrocholate into the biliary and pancreatic duct. 5 rats were treated as normal control. Other 75 Sprague-Dawley (SD) rots were randomly divided into sham operations(SO) group (n =25), ANP group (n =25) and PD98059 group (n =25). The rats were sacrificed at 15 min, 30 min, 1 h, 3 h and 6 h after ANP induction, the blood and pancreatic sample were taken. Pathological changes of pancreas were observed with light microscope and scored. The serum level of TNF-α and IL-1β was determined by ELISA. MPO activities in pancreas were measured by enzyme chemistry assay. Western blotting was performed to determine the phosphorylations of ERK1/2 in the pancreas homogenates. Results There was no significant pathologic changes in rats of SO group;but significant injuries occurred in ANP group, the pathologic score at 3 h was 9.9 ± 0.4;the extent of injuries attenuated in PD98059 group, the pathologic score at 3 h was 4.0 ± 0.4 (P < 0.05). The serum levels of TNF-α at 3 h in SO, ANP and PD98059 groups were (65.8 ± 20.5) pg/ml, (286.5 ± 50.3) pg/ml, (180.4±32.9)pg/ml, respectively;the serum levels of IL-1β at 3 h in SO, ANP and PD98059groups were (85.8 ± 25.5) pg/ml, (293.8 ± 46.3) pg/ml, (200. 5 ± 33.6) pg/ml, respectively;MPOactivities in pancreas were (0. 19 ± 0.02)U/g, (0.61±0.05)U/g, (0.52±0.03) U/g, and the values in ANP and PD98059 groups were significantly higher than those in SO group, while the values in PD98059 group were significantly lower than those in ANP group (P < 0.01). The expression of ERK1/2 phosphorylation in normal pancreas was 1100 ± 141, the expressions of ERK1/2 phosphorylation in ANP group at 15 min, 30 min were 5300 ± 486, 5621 ± 384, respectively;the expressions began to decrease 1 h later and returned the similar level as SO group at 6 h;the expressions of ERK1/2 phosphorylation in PD98059 group at 15 min, 30 rain were 4200 ± 370, 3600 ± 290, respectively;which were signifieanfly lower than those in ANP group (all P value < 0. 01). Conclusions The ERK1/2 signal transduetion pathway plays an important role in the pathogenesis of ANP. Inhibition of ERK1/2 phosphorylation by PD98059 may decrease the production of IL-1β, TNF-α and pancreatic MPO, attenuate the extent of pancreatic pathologic injuries.

Conditionally-replicating adenovirus (CRAd) therapy is currently being tested against pancreatic cancer and has shown some promise. To improve the efficacy, a novel virus CRAd-Cans was designed by deletion of E1B-55 kDa gene for selective replication in tumor cells, as well as carrying a new angiogenesis inhibitor gene, canstatin. CRAd-Cans mediated higher expression of canstatin in BxPC-3 pancreatic cancer cell line compared to the replication-deficient adenovirus Ad5-Cans. The modified CRAd-Cans manifested the same selective replication and cytocidal effects in pancreatic cancer cells as ONYX-015 in vitro, yet showed greater reduction of tumor growth in nude mice with markedly prolonged survival rate in vivo (P < 0.05), compared to that of either ONYX-015 or Ad5-Cans. Pathological examination revealed viral replication, decreased microvessel density and increased cancer cell apoptosis in CRAd-Cans-treated xenografts. The results suggest that the novel oncolytic virus CRAd-Cans, showing synergistic effects of oncolytic therapy and anti-angiogenesis therapy, is a new promising therapeutics for pancreatic cancer.

Objective To investigate the expression of Fascin mRNA and its protein in human pancreatic carcinoma cell line and pancreatic cancer tissues and to explore the relationship between the expression of Fascin protein and the clinicopathologic parameters. Methods The expression of Fascin mRNA in pancreatic cancer cell lines (SW1990, Patu8988, BxPC3, cfPAC1) were measured by RT-PCR and the expression of Fascin protein in 54 samples of pancreatic career tissues and 42 adjacent normal pancreatic tissues was detected by immunohistochemical method. Results The expression of Fascin mRNA was confirmed in 3 of 4 pancreatic cancer cell lines (SW1990, Patu8988, cfPAC1), but not in the cell line of BxPC3; the rate of positive expression of Fascin protein in pancreatic cancer tissues was 64.81% (35/54) and there was no positive expression in adjacent normal pancreas tissues; the expression of Fascin protein correlated with the differentiation degree (P < 0.01) and with the lymphatic metastasis of the carcinoma (P <0.05), but not with the size and distant metastasis of the carcinoma (P > 0. 05). Conclusions Fascin protein was highly positively expressed in pancreatic cancer tissues, and the expression of Fascin protein may help diagnose pancreatic, carcinoma and predict the malignant degree.

今天,我们迎来了一个值得庆贺的日子.经中华医学会、中国科学技术协会批准,并报中华人民共和国新闻出版总署审核,本刊正式加入中华医学会系列杂志,更名为<中华胰腺病杂志>.

背景:细胞因子具有免疫佐剂效应,但将其用作幽门螺杆菌（H.pylori）核酸疫苗佐剂的研究报道尚少。目的:构建同时含H.pylori尿素酶B亚单位（ureB）基因和小鼠白细胞介素-2（IL-2）基因的重组活减毒鼠伤寒沙门菌核酸疫苗,体外鉴定其表达蛋白的免疫原性,体内检测其对H.pylori感染的免疫保护作用。方法:以聚合酶链反应（PCR）扩增H.pyloriureB基因和小鼠IL-2基因,分别插入pUCmT载体,测序,通过一系列酶切、连接反应分别克隆入真核表达载体pIRES,酶切、PCR鉴定;重组质粒pIRES-ureB和pIRES-ureB-IL-2分别转化减毒鼠伤寒沙门菌LB5000,抽提质粒,进一步转化终宿主菌SL7207,反复传代培养。以LipofectamineTM2000将重组质粒分别体外转染COS-7细胞,蛋白质印迹法检测表达蛋白的免疫原性。以疫苗菌经口接种小鼠,4周后予H.pylori攻击,攻击后4周鉴定H.pylori感染状况。结果:测序结果显示扩增出的ureB和IL-2基因序列与GenBank中的H.pyloriureB和小鼠IL-2序列一致,酶切、PCR鉴定证实ureB和IL-2基因已克隆入pIRES载体,并成功构建了稳定的含H.pyloriureB和小鼠IL-2基因的重组活减毒鼠伤寒沙门菌核酸疫苗。蛋白质印迹法显示,pIRES-ureB-IL-2转染的COS-7细胞表达特异性UreB和IL-2蛋白。体内实验显示,疫苗接种组小鼠的免疫保护率显著高于PBS对照组（P＜0.01）,其中ureB-IL-2疫苗组又显著高于ureB疫苗组（87.5%对62.5%,P＜0.05）。结论:成功构建了编码H.pyloriureB和免疫佐剂IL-2基因的重组活减毒鼠伤寒沙门菌核酸疫苗,体外实验证实其可表达具有免疫原性的抗原蛋白和佐剂蛋白,体内实验证实其对小鼠H.pylori感染具有免疫保护性,免疫佐剂IL-2可提高核酸疫苗的免疫保护率。

Objective To detect mucin(MUC1,MUC2,MUC5AC) expressions in endoscopic ultrasound guided fine needle aspiration(EUS-FNA) specimens of the pancreatic neoplasms lesions and evaluate their diagnostic value.Methods The expression profile of MUC1,MUC2,MUC5AC from 54 EUS-FNA samples of pancreatic occupying lesions were examined by immunohistochemistry with mono- clonal antibodies.The results were correlated to the eytohistologic and clinical diagnosis of pancreatic cancer.Results Thirty-eight of the 54 patients had pancreatic cancer,6 patients had benign tumor,10 patients had chronic pancreatitis.The sensitivites of cytology and histology in diagnosing pancreatic cancer were 31.6%and 47.4%,respectively.The prevalence of MUC1,MUC2 and MUC5AC expres- sion in EUS-FNA samples of pancreatic cancer were 81.6%(31/38),10.5%(4/38),84.2%(32/38), respectively,and those in benign pancreatic neoplasms were 25%(4/16),31.3%(5/16),43.8%(7/16),respectively.There was statistically significance in MUCland MUCSAC expression between the two groups(P0.01).Furthermore,MUC1 expression in pancreatic cancer had positive correlation with clinical stage and lymphatic metastasis.Combined measurement of MUC1 and MUC5AC expression and cytohistologic analysis in EUS-FNA specimens could increase sensitivity to 89.5%in diagnosing pancreatic cancer.Conclusions Determination of MUC1 and MUCSAC expression in EUS-FNA speci- mens from pancreatic tissue will be helpful in diagnosing pancreatic cancer.In addition,MUC1 expres- sion can predict the clinical stages and lymphatic metastasis of cancer.

迷走神经背核(DMN)是重要的内脏运动核团,参与胰腺外分泌功能的调节.有研究表明,生长抑素(SS)不是通过迷走传入和传出神经纤维发挥抑制其胰腺外分泌功能的效应,而是在中枢发挥对胰腺外分泌功能的抑制作用[1].本研究采用人工合成生长抑素八肽奥曲肽,观察DMN注射SS对基础状态胰腺外分泌功能的影响.

目的:研究络沙坦(Losartan)对急性坏死性胰腺炎(ANP)大鼠肺损伤的保护作用.方法:SD大鼠30只随机分为3组:正常对照组、ANP组、Losartan治疗组.采用大剂量精氨酸腹腔注射诱导ANP模型,治疗组于造模后30 min给予Losartan200 μg/kg,2次,每次间隔1 h.各组于造模后24 h处死大鼠,观察大鼠血浆血管紧张素Ⅱ(AngⅡ)、肾素(PRA)、淀粉酶(AMY)、TNF-α、IL-1β、肺组织髓过氧化物酶(MPO)、肺湿/干重比值、胰腺/体重比值、胰腺和肺组织病理变化.结果:ANP组血浆AngⅡ、PRA、AMY、TNF-α、IL-1β、MPO、肺湿/干重比值、胰腺/体重比值较对照组明显升高;Losartan治疗组血浆AngⅡ、PRA较ANP组变化不明显,AMY、TNF-α、IL-1β、MPO、肺湿/干重比值、胰腺/体重比值较ANP组明显下降,胰腺和肺组织病理损伤明显减轻.结论:络沙坦对血浆AngⅡ、PRA无明显影响,可以减少TNF-α、IL-1β、MPO的产生,对ANP肺损伤具有保护作用.

在胰腺癌多步骤、多阶段发生过程中有多种肿瘤相关基因参与.p16基因是其中一个重要的抑癌基因,参与细胞周期的调控,控制细胞的生长和分化.大量研究表明,多种肿瘤细胞中p16基因通过突变、缺失、高甲基化等方式失活,造成p16蛋白功能丧失,从而导致肿瘤细胞恶性生长。

Objective To construct a nucleic acid vaccine expressing H.pylori HpaA and inter- leukin-2 gene and to identify the immunogenicity of the vaccine proteins in vitro and protection in vivo. Methods The H paA gene fragment was amplified by polymerase chain reaction(PCR) from the genomic DNA of the standard H.pylori strain 17874.Mouse interlukin(IL)-2 gene was amplified from pClneo- IL-2.The HpaA and IL-2 were cloned into pUCmT vector.After DNA sequences of the amplified HpaA gene and IL-2 were confirmed,both were cloned into the eukaryotic expression vector pIRES through a serial of enzyme digestion and ligation reactions.The recombinant plasmids were screened by PCR and restriction enzyme digestion.Then,recombinant pIRES-HpsA-IL-2 was transfected to COS-7 cells using Lipofectamine~(TM)2000.The immunogenicity of HpaA and IL-2 protein was detected by SDS- PAGE and Western blot.The recombinant plasmids were transformed to LB5000 and then to final host SL7207.The recombinant strains were passaged repeatedly.The mice were challenged with H.pylori after 4 weeks of inoculation of nucleic acid vaccine.H.pylori infection was detected by rapid urease test.Results The amplified HpaA gene fragment and IL-2 were confirmed by sequence analysis.The eukaryotic expression vector plRES and the pIRES-HpaA-IL-2 construction were confirmed by PCR and restriction digestion.The expressions of HpaA(30 000) and IL-2(14 000)protein by pIRES-HpaA-IL- 2 were detected by Western blot.The in vivo study showed that 75.0% and 58.4% of mice vaccinated by HpaA-IL-2 and HpaA,respectively,were protected anaigst H.pylory infection,which was signifi- cant different in comparison with PBS control (P0.01).Conclusions A recombinant attenuated nu- cleic acid vaccine HpaA-IL-2 encoding both HpaA and mouse IL-2 was successfully constructed and its immunogenicity in vitro and protection in vivo were confirmed.The IL-2 can enhance the protective efficacy in immunized mice.

Objective To investigate the distribution of neurons expressing Fos protein in central nervous system (CNS) following esophageal mucosal acid exposure,and to map the contribution of spe- cific brain areas in sensitizing responsivity and emphasize the coding change of CNS to the esophageal acid stimulation.Methods Thirty-six healthy Sprague-Dwley rats were randomly divided into five groups. Group A (n=6) was normal group of home cage control animals to which no stimulation was given. Group B (n=7) was saline group which received esophageal perfusion with normal saline solution (0.9% NaCl).Group C (n=8) was treated with esophageal mucosal acid exposure containing 0.1 mol/L HCl. Group D (n=7) was sensitized by ovalbumin.Group E (n=8) received basal ovalbumin-sensitization plus esophageal mucosal acid exposure.The rat model of esophageal visceral hypersensitivity was estab- lished by the basic ovalbumin-sensitization combined with intra-esophageal mucosal acid exposure.The neuronal expressions of c-fos proto-oncogene were detected with immunohistochemical counter-staining and computerized color image analyzer under various conditions.Results The rats in model group with basic ovalbumin-sensitization plus esophageal acid perfusion initiated a high density expression of c-fos- immunoreactive(Fos-IR) neurons in multineuronal networks.A significantly higher number of Fos positive neurons was found in the model group than those in the corresponding regions of other groups (P＜0.05) in the following brain areas:frontal and parietal cortex,insular cortex,cingulated cortex,central amyg- daloid nucleus,the K(?)lliker-Fuse nucleus,the nucleus ambiguus,parabrachial nucleus,hypothalamic paraventricular nucleus,paraventricular thalamic nucleus,paratrigeminal nucleus,the nucleus of solitary tract,area postrema,reticular nucleus of medulla,whereas no significant difference was found in the dorsal motor nucleus of the vagus,supraoptic nucleus,periaqueductal gray matter or orbital part of infe- rior frontal gyrus.The values of Fos-IR neurons were also increased in the central amygdala,parabrachi- al nucleus,paraventricular nucleus,the paratrigeminal nucleus and NTS in the model group than that in the corresponding regions of other groups (P＜0.05).Conclusion The basic ovalbumin-sensitization fa- cilitated dramatically the c-fos expression evoked by esophageal acid perfusion,suggesting that visceral hypersensitivity induced by ovalbumin may alter cortical reactivity processing of esophageal acid stimula- tion in brain areas.

Objective To express the recombinant human canstatin protein, and to examine its biological activity. Methods Canstatin cDNA was cut off from the plasmid pUCm-T/canstatin with restriction enzymes BamHⅠ and Hind Ⅲ. The cDNA fragment was then ligated into the correspondence sites of plasmid pET-22b(+) by T4 DNA ligation enzyme and transformed into E.coli BL21 which was induced to express proteins with isopropyl-1-thio-b-dgalactopyranoside (IPTG). The expressed proteins were analyzed by SDS-PAGE and purified through Ni-NTA column affinity chromatography. Chick chorioallantoic membrane (CAM) assay was performed to determine the activity of the recombinant protein. Results Canstatin cDNA from pUCm-T showed one clear objective DNA band with electrophoresis. Seven of positive colonies were selected and identified by restriction enzyme analysis with BamH Ⅰ and Hind Ⅲ. Electrophoresis revealed that all selected colonies had two specific bands,one near the location of primary plamid,the other near that of objective gene fragment. After IPTG induction, there was a new protein band about 24 000 on SDS-PAGE.The induced product over total bacterial proteins in 1,2, 3. and 4 hours after induction was 18. 2%, 18. 8%, 23.0% and 23.4%, respectively, by densitometry examination. CAM assay demonstrated that the recombinant canstatin protein significantly inhibited the embryonic neovascularization in a dose-dependent manner. Conclusion The prokaryotic expression vector of human canstatin gene has been successfully constructed, laying the foundation for further clinical study.

Objective To clone human pancreatic cancer gene PTCH and construct pET22b/PTCH expression plasmid. The protein was used to immunize rabbits to prepare anti-PTCH multiclonal antibody, which was then used to detect the expression of PTCH in pancreatic cancer. Methods Total RNA was isolated from human pancreatic cancer cell line SW1990. The PTCH gene was amplified from the total RNA by RT-PCR. The resulting product was cloned into pET22b vector. The pET22b/PTCH construct was then transformed into E.coliBL21-CodonPlusTM-RP, and the gene was sequenced. The fusion protein was expressed by IPTG and verified by Western blot. The expressed protein was purified with a His. Bind column. Results A human pancreatic cancer gene with a reading frame of 789 bp was successfully cloned from human pancreatic cancer cell SW1990, which had the same sequence as that of PTCH gene in Genebank. The expression of pET22b/PTCH was proved by Western blot, and the fusion protein was also purified by Ni-NTA affinity chromatography. Conclusions Human pancreatic cancer gene PTCH was successfully cloned and expressed in E. coli, and the fusion protein has been purified by Ni-NTA affinity chromatography, which would provide a useful tool in the study of Hedgehog signal in pancreatic cancer.

AIM:To construct a live attenuated Salmonella typhimurium (S. typhimurium) strain harboring the H pylori neutrophil activating protein (HP-NAP) gene as an oral recombinant DNA vaccine, and to evaluate its immunogenicity.METHODS:By genetic engineering methods, the genomic DNA of H pylori was extracted as a template. The total length of the HP-NAP gene was amplified by polymerase chain reaction (PCR) and cloned into pBT vector for sequencing and BLAST analysis, then subcloned into a eukaryotic expression vector pIRES followed by PCR identification and restriction enzyme digestion. The identified recombinant plasmid pIRES-NAP was transfected into COS-7 cells for target fusion protein expression, and its antigenicity was detected by Western blotting. Then the recombinant plasmid was transformed into a live attenuated S. typhimurium strain SL7207 as an oral vaccine strain, and its immunogenicity was evaluated with animal experiments.RESULTS:A 435 bp product was cloned using high homology with HP-NAP gene in GenBank (more than 98%). With identification by PCR and restriction enzyme digestion, a recombinant eukaryotic expression plasmid pIRES-NAP containing the HP-NAP gene of H pylori was successfully constructed. The expressed target protein had a specific reaction with H pylorii whole cell antibody and showed a single strip result detected by Western blotting. Oral immunization of mice with recombinant DNA vaccine strain SL7207 (pIRES-NAP) also induced a specific immune response.CONCLUSION:The successful construction of HP-NAP oral DNA vaccine with good immunogenicity may help to further investigate its immunoprotection effects and develop vaccine against H pylori infection.

Objective To clone human pancreatic cancer gene PTCH,construct the recombinant(expression) plasmid PET22b/PTCH and express the fusion protein.Methods The PTCH gene was(amplified) by RT-PCR from the total RNA extracted from human pancreatic cancer strain SW1990. The amplified product was inserted into the vector PET22b to construct the recombinant expression plasmid PET22b/PTCH,which was transformed into E.coliBL21-CodonPlus~(TM)-RP and then identified by(sequence) analysis.The expression of fusion protein was induced with IPTG and verified by Western blot method.Results A human pancreatic cancer gene with a reading frame of 789 bp was successfully cloned from human pancreatic cancer strain SW1990,which had the same sequence as that of PTCH gene in Genbank.The expression of PET22b/PTCH was proved by Western blot.Conclusion Human(pancreatic) cancer gene PTCH was successfully cloned and constructed with PET22b plasmid.The(prepared) fusion protein lays the basis for further study.

AIM:To examine the effect of canstatin, a newly discovered endogenous inhibitor of angiogenesis, in the treatment of pancreatic cancer in vivo.METHODS:The canstatin cDNA fragment was synthesized and amplified from the total RNA extracted from human placenta tissues by RT-PCR. The resulting product was firstly cloned into pUCm-T vector, then into plasmid pET-22b (+) and transformed into E. coli BL21. Isopropyl-1-thio-b-Dgalactopyran-oside (IPTG) was used to induce the expression of canstatin protein and affinity chromatography was used to purify the protein. To determine the activity of purified recombinant human canstatin (rhCanstatin), orthotopic xenograft human pancreatic cancer models were established. Human pancreatic cancer cells (SW1990) were injected into the pancreas of BALB/c nude mice. Twenty-four nude mice with orthotopic xenograft tumor were randomly divided into 3 groups 10 d after the inoculation, and were treated with PBS 0.3 mL, or canstatin 5 mg/kg, or 10 mg/kg per day for 3 wk intraperitoneally. When the experiment was over, all tumors were resected and the effects of rhCanstatin on tumor growth, microvessel density (MVD) were analyzed.RESULTS:After IPTG induction, SDS-PAGE showed a new monomeric 24 kDa protein band. This protein was purified through affinity chromatography and refolded through dialysis with a final concentration of 60 mg/L. In orthotopic pancreatic cancer models, the final tumor volume in groups treated with PBS, canstatin 5 mg/kg, 10 mg/kg were 355.21+/-39.54 mm3, 112.73+/-10.47 mm3, and 61.75+/-6.99 mm3 respectively. The immunohistochemical examination showed that the MVD in tumors treated with canstatin was significantly less than that in other group.CONCLUSION:These findings demonstrate that the rhCanstatin effectively retards the growth of pancreatic cancer in a dose-dependent manner through inhibiting angiogenesis and may be a promising therapeutic agent for pancreatic cancer treatment in the clinic.

Objective To investigate the effect of esophageal mucosal acid exposure on visceral sensation of patients with non-erosive gastroesophageal reflux disease (NERD) and to evaluate the role of visceral hypersensitivity in NERD pathogenesis. Methods We recruited 21 NERD patients and 10 normal healthy volunteers. Mechanical distentions stimulation and acid perfusion through esophagus were performed using the balloon-affixed and polyvinyl multilumen catheter. Esophageal visceral perception thresholds were examined before and after acid perfusion with esophageal balloon distention by means of a computer-controlled barostat. Results As compared with healthy subjects, NERD patients demonstrated significantly lower initial perception threshold and maximally tolerated pain threshold (P0.001) to esophageal mucosal distention before esophageal mucosal acid exposure. After acid perfusion, the initial perception threshold and maximally tolerated pain threshold of NERD patients were significantly lower than the basic values (P=0.015), the initial volume-to-sensory threshold of normal control subjects also lower than the basic values (P0.05), but infused acid had no effect on their pain threshold. The maximal pain thresholds induced by esophageal balloon distention in NERD patients undergone acid perfusion was significantly lower than that in control group (9.70±3.06) ml vs (22.10±4.91) ml, P0.001. No remarkable changes in visceral perception thresholds were found in two groups before and after saline infusion. Conclusion The sensitization of esophageal mucosal chemoreceptors after acid infusion exerts a significant influence on the pressure-sensitive mechanoreceptors to mechanical distentions stimulation. There is the cooperative interaction between acid-sensitive chemoreceptors and pressure-sensitive mechanoreceptors in process of esophageal visceral hypersensitivity.

Objectives To verify if chemotherapy drug gemcitabine could induce a change of protein expression in pancreatic cancer cell line SW-1990, and to provide evidence for clinical therapy. Methods We use two-dimensional gel eleclrophoresis(2-DE), mass speclrornetry and bio-information methods to compare the change of protein expression before and after gemcitabine and 5-FU treatment of cell line SW-1990, and identify the discrepant protein expression. Results The concentration of gemcitabine, that can suppress 50 percent of the pancreatic cancer cells was 1-100 ng/ml, while same suppression for 5-FU was 250-2500 ng/ml. Six discrepant protein expressions, one in 5-FU group and 5 in gemcitabine group were found. Conclusions Gemcitabine has better therapeutic effects on the growth of pancreatic cancer cell line SW-1990 than that of 5-FU. Gemcilabine was involved in sugar and fat metabolism, and it could induce some changes of protein expression, for example β-actin and MGC: 19713, which is of somewhat importance for clinical investigation of pancreatic cancer therapy.

Objective To investigate the protective effect of losartan on acute necrotic pancreatitis(ANP) in rats. Methods Forty SD rats were randomly divided into 4 groups: control group, ANP group, losartan preconditioned group, and losartan treatment group. The ANP model was induced by intraperitoneal injection of L-arginine. Rats in losartan preconditioned group were injected with 200 μg/kg losartan twice hourly 90 min before induction of ANP. Rats in losartan treatment group was injected with losartan 200 μg/kg twice hourly 30 minutes after the induction of ANP. All rats were killed 24 h after induction of ANP and the levels of angiotensinⅡ, renin, amylase, TNF-α, IL-1β in blood, and the ratio of pancreatic weight to body weight were measured. The mRNA of angiotensinogen, rennin and angiotensinⅡ receptor AT1 were analyzed by RT-PCR. Histopathological changes of pancreas were also observed. Results Compared with control group, the levels of angiotensinⅡ, renin, amylase, TNF-α, IL-1β in plasma and the ratio of pancreatic weight to body weight were all significantly increased in ANP group; and mRNA expression of angiotensinogen, rennin, and angiotensinⅡ receptor AT1 were also increased. Compared with the ANP group, the levels of AMY, TNF-α, and IL-1βin both losartan preconditioned group and treatment group were significantly reduced, but the levels of angiotensinⅡ and rennin had no obvious changes. Losartan also ameliorated the pancreas histopathologic inflammation. Conclusions Losartan has no obvious influence on plasma Ang II, PRA, angiotensinogen, rennin, and AT1, but can decrease the production of TNF-αand IL-1β, thus protecting patients with ANP.

目的 观察S100A4、S100A6、S100P mRNA在胰腺癌中的表达,探讨S100亚型的分布规律及与胰腺癌发生、发展的关系.方法 选取胰腺癌和癌旁正常胰腺组织各20例,用半定量RT-PCR方法检测S100A4、S100A6、S100P mRNA表达水平.结果 胰腺癌组织中S100A4、S100A6、S100P mRNA均为高表达,与癌旁正常胰腺组织比较,均具有显著性差异(P＜0.01).S100A4 mRNA的表达水平与胰腺癌的肿瘤分化、淋巴结转移及远处转移相关,与肿瘤大小无关;S100A6、S100P mRNA在胰腺癌中的高表达则与胰腺癌的临床病理特征无关(P＞0.05).结论 S100A4、S100A6、S100P与胰腺癌的发生有关,S100A4与胰腺癌的分化程度、淋巴结转移和远处转移有关,S100A6、S100P与胰腺癌的临床病理特征无关。