AIM To explore the effect and mechanism ofgastrin and its antagonists proglumide and somatostatin on coIorectal carcinoma and their clinical significance.METHODS A model of transplanted human colonic carcinoma was est...AIM To explore the effect and mechanism ofgastrin and its antagonists proglumide and somatostatin on coIorectal carcinoma and their clinical significance.METHODS A model of transplanted human colonic carcinoma was established from SW480cell line in gymnomouse body. The volume andweight of transplanted carcinoma was observedunder the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content ot carcinoma cell was determined by redioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viabIe cells was determined by MTT colorimetric analysis, lP3 content was determined by radioimmunoassay, Ca2+ concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc,C-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immunocytochemistry SP method. Argyrophilianucleolar organizer regions was determined withargyrophilia stain.RESULTS The volume, weight, cAMP, DNAand protein content in carcinoma cell, cellamount and proliferation index of S and G2Mphase in PG group were all significantly higher than those of control group. When PG was at theconcentration of 25 mg/ L, the amount of viablecells, lP3 content and Ca2+ concentration in celland membrane PKC activity in PG group weresigniticantly higher than those in control group;when PGL was at a concentration ot 32 mg/L,they dropped to the lowest level in PG (25 mg/L)+ PGL group, but without significant differencefrom the control group. The positive expression rate of gastrin, c-myc, c-fos and rasp21 in carcinoma tissue was 39 .6%, 54 .2%, 47. 9% and54 .2% resPectively and significantly higher than that in mucosa 3 cm and 6 cm adjacent tocarcinoma tissue and normal colorectal mucosa.The positive expression rate of gastrin of highlydifferentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocarcinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3 cm and 6 cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin-negative group.CONCLUSION Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL hasno obvious effect on the growth of human colonic carcinoma SW480 cell line, but couldinhibit the growth-promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directlybut also depress the growth-promoting effect ofgastrin on the transplanted carcinoma. Somecolorectal carcinoma cells can produce and secrete gastrin through autocrine, highly-differentiated adenocarcinoma express the highest level gastrin. Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene omyc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL,somatostatin of patients with colorectalcarcinoma.展开更多
AIM To study the role of cholecystokinin octapeptide ( CCK-8), β-endorphin ( β-EP), and gastrin in an anorexic infantile rat model and no subsequent regulation of nose peptides by the Yunpi complex prescription ErB...AIM To study the role of cholecystokinin octapeptide ( CCK-8), β-endorphin ( β-EP), and gastrin in an anorexic infantile rat model and no subsequent regulation of nose peptides by the Yunpi complex prescription ErBao Granule.METHODS We fed infantile rats with special prepared forage. A liquid extract of ErBao Granule was administered to the rats daily for 3weeks, CCK-8, β-EP, and gastrin concentrations in hypothalamus, gastric antrum, and plasma of the rats were measured by radioimmunoassay,and were compared with controls.RESULTS Treatment of rats with ErBao Granule inhibited CCK-8 secretion and increased β-EP and gastrin secretion. CCK-8 concentration in hypothalamus and plasma of model control group increased significantly and correlated negatively with food intake of models.respectively. β-EP concentration in gastric antrum and plasma of model control group decreased significantly and showed a positive correlation with food intake of models,respectively. Hypothalamus concentration of β-EP was similar in models and controls. Gastrin concentration in gastric antrum of models was lower than in the blank control group, and correlated positively to food intake of models.Finally, CCK-8 concentrations in plasma of rats showed a positive correlation with plasma β-EP(r- 0.68, P＜0.05).CONCLUSION The increased plasma and hypothalamus concentration of CCK-8,decreased gastric antrum and plasma level of β-EP. and decreased gastric antrum concentration of gastrin are associated significantly with the anorexia of infantile anorexic rat models produced by special forage. ErBao Granule can reverse these changes, which may be the major mechanisms of ErBao Granule simulating feeding.展开更多
Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between...Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori(H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2(COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.展开更多
BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the...BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis. METHODS: The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay. RESULTS: The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01).CONCLUSIONS: The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.展开更多
INTRODUCTIONGastrin is atrophic gastrointestinal hormone whichis secreted by G cell.Gastrin has long beenconsidered a growth stimulatory hormone formucosa of the gastrointestinal tract.The growthresponses of certain c...INTRODUCTIONGastrin is atrophic gastrointestinal hormone whichis secreted by G cell.Gastrin has long beenconsidered a growth stimulatory hormone formucosa of the gastrointestinal tract.The growthresponses of certain colorectal cancer cells,andxenografts,can be stimulated by endogenousgastrin.Protein kinase C (PKC) is a family ofisozymes that plays a crucial role in transducingsignals of many hormones,growth peptides,展开更多
AIM To investigate the changes of gastricmucosal ascorbic acid secretion in patients withnonulcer dyspepsia and the effect of gastrin onit,and to relate any observed changes to H.pylori infection and mucosal histology...AIM To investigate the changes of gastricmucosal ascorbic acid secretion in patients withnonulcer dyspepsia and the effect of gastrin onit,and to relate any observed changes to H.pylori infection and mucosal histology.METHODS Ascorbic acid secretions in patientswere examined by collecting continuouslygastric juice for one hour after having aspiratedand discarded fasting gastric juice.Using theclearance rate(mL/min)of ascorbic acid fromblood to gastric juice represented ascorbic acidsecretion in the gastric mucosa.Ascorbic acidconcentrations in plasma and juice weremeasured by ferric reduced method.RESULTS Gastric ascorbic acid secretions inH.pylori-positive patients(1.46 mL/min,range0.27-3.78)did not significantly differ fromthose in H.pylori-negative patients(1.25 mL/min,0.47-3.14)(P】0.05).There were nosignificant differences in ascorbic acidsecretions between patients with mild(1.56 mL/min,0.50-3.30),moderate(1.34 mL/min,0.27-2.93)and severe(1.36 mL/min,0.47-3.78)inflammation(P】0.05).There were nosignificant differences in ascorbic acidsecretions between patients without activity(l.45mL/min,0.27-3.14)and with mild(1.32mL/min,0.61-2.93),moderate(1.49mL/min,0.50-3.78)and severe(1.43 mL/min,0.51-3.26)activity of chronic gastritis either(P】0.05).Ascorbic acid secretions in patientswith severe atrophy(0.56 mL/min,0.27-1.20)were markedly lower than those in patientswithout atrophy(1.51 mL/min,0.59-3.30)and with mild(1.43 mL/ min,0.53-3.78)andmoderate(1.31 mL/min,0.47-3.16)atrophy(P【0.005).There was a significant negativecorrelation between ascorbic acid secretion andseverity of atrophy(correlation coefficient=-0.43,P【0.005).After administration ofpentagastrin,ascorbic acid secretions weremarkedly elevated(from 1.39 mL/min,0.36-2.96 to 3.53mL/min,0.84-5.91)(P【0.001).CONCLUSION Ascorbic acid secretion ingastric mucosa is not affected by H.pyloriinfection.Gastric ascorbic acid secretion ismarkedly related to the severity of atrophy,whereas not related to the severity ofinflammation and activity.Gastrin may stimulategastric ascorbic acid secretion.A decreasedascorbic acid secretion may be an importantfactor in the link between atrophic gastritis andgastric carcinogenesis.展开更多
AIM:To explore the role and mechanisms of extracellular signal-regulated protein kinase-mitogen-activated protein kinase(ERK-MAPK) signaling in pentagastrinregulated growth of large intestinal carcinoma.METHODS:HT-29 ...AIM:To explore the role and mechanisms of extracellular signal-regulated protein kinase-mitogen-activated protein kinase(ERK-MAPK) signaling in pentagastrinregulated growth of large intestinal carcinoma.METHODS:HT-29 cells were incubated in different media and divided into the control group,pentagastrin group,proglumide group,and pentagastrin + proglumide group.No reagent was added to the control group,and other groups were incubated with reagent at different concentrations.Changes in proliferation of HT-29 cells were detected by MTT assay,and the optimal concentrations of pentagastrin and proglumide were determined.The changes in proliferation index(PI) and apoptosis rate(AR) of HT-29 cells were detected by Annexin V-fluorescein isothiocyanate flow cytometry.mRNA expression of pentagastrin receptor/cholecystokinin-B receptor(CCK-BR),ERK1/2 and K-ras were detected by reverse transcriptase polymerase chain reaction.The protein and phosphorylation level of ERK1/2 and K-ras were detected by western blotting.All data were analyzed by analysis of variance and SNK-q test.RESULTS:The proliferation of HT-29 cells was stimulated by pentagastrin at a concentration of 6.25-100 mg/L,and the optimal concentration of pentagastrin was 25.0 mg/L(F = 31.36,P < 0.05).Proglumide had no obvious effect on the proliferation of HT-29 cells,while it significantly inhibited the proliferation of HT-29 cells stimulated by pentagastrin when the concentration of proglumide was 8.0-128.0 mg/L,and the optimal concentration was 32.0 mg/L(F = 24.31,P < 0.05).The PI of the pentagastrin(25.0 mg/L) group was 37.5% ± 5.2%,which was significantly higher than 27.7% ± 5.0% of the control group and 27.3% ± 5.8% of the pentagastrin(25.0 mg/L) + proglumide(32.0 mg/L) group(Q = 4.56-4.75,P < 0.05).The AR of the pentagastrin(25.0 mg/L) group was 1.9% ± 0.4%,which was significantly lower than 2.5% ± 0.4% of the control group and 2.4% ± 0.3% of the pentagastrin(25.0 mg/L) + proglumide(32.0 mg/L) group(Q = 4.23-4.06,P < 0.05).mRNA expression of CCK-BR was detected in HT-29 cells.The phosphorylation levels of ERK1/2 protein and phosphorylated K-ras protein of the pentagastrin group were 0.43% ± 0.04% and 0.45% ± 0.06%,which were significantly higher than 0.32% ± 0.02% and 0.31% ± 0.05% of the control group(Q = 7.78-4.95,P < 0.05),and 0.36% ± 0.01% and 0.35% ± 0.04% of the pentagastrin + proglumide group(Q = 5.72-4.08,P < 0.05).There were no significant differences in the mRNA and protein expression of ERK1/2 and K-ras among the control,pentagastrin,proglumide and pentagastrin + proglumide groups(F = 0.52,0.72,0.78,0.28;P > 0.05).CONCLUSION:Gastrin stimulates proliferation of HT-29 cells and inhibits apoptosis by upregulating phosphorylation of ERK and K-ras through the Ras-Raf-MEK1/2-ERK1/2 pathway,and this is restrained by proglumide.展开更多
BACKGROUND Serum gastrin-17(G-17),pepsinogen I(PGI),and pepsinogen II(PGII)concentrations regulate gastric acid secretion,and hypersecretion of gastric acid increases the risks of peptic ulcer and upper gastrointestin...BACKGROUND Serum gastrin-17(G-17),pepsinogen I(PGI),and pepsinogen II(PGII)concentrations regulate gastric acid secretion,and hypersecretion of gastric acid increases the risks of peptic ulcer and upper gastrointestinal bleeding.These associations suggest that serum G-17,PGI,and(or)PGII may predict gastrointestinal bleeding risk among peptic ulcer patients.AIM To evaluate the efficacies of serum G-17,PGI,PGII,and PGI/PGII ratio(PGR)for predicting upper gastrointestinal bleeding among peptic ulcer patients.METHODS A total of 199 patients diagnosed with peptic ulcer confirmed by gastroscopy and positivity for Helicobacter pylori by the 14C-urea breath test were recruited,including 107 patients with simple peptic ulcer and 92 cases complicated by upper gastrointestinal bleeding.Serum PGI,PGII,G-17,and PGR were measured by immune methods and compared between bleeding and non-bleeding groups by univariate analysis.The specificity and sensitivity of PGs and G-17 for evaluating upper gastrointestinal bleeding risk were then assessed by constructing receiver operating characteristic(ROC)curves.RESULTS Serum G-17 was significantly higher among peptic ulcer patients with upper gastrointestinal bleeding compared to simple peptic ulcer patients(25.34±14.29 vs 8.84±8.03 pmol/L,t=9.822,P<0.01),whereas serum PGI,PGII,and PGR did not differ significantly between bleeding and non-bleeding groups(all P>0.05).The risk of bleeding was significantly higher among peptic ulcer patients with elevated serum G-17(>15 pmol/L)compared to patients with normal or low serum G-17(73.2%vs 27.4%,χ2=40.72,P<0.01).The area under the ROC curve for serum G-17 was 0.866±0.024,and a cut-off of 9.86 pmol/L yielded 90.2%sensitivity and 68.2%specificity for distinguishing peptic ulcer with and without upper gastrointestinal bleeding.CONCLUSION Serum G-17 is significantly upregulated in peptic ulcer patients and higher levels are predictive of upper gastrointestinal bleeding.Conversely,serum PGI,PGII,and PGR have no predictive value.Further prospective studies are warranted to examine if high G-17 can be used to assess risk of bleeding prior to onset.展开更多
文摘AIM To explore the effect and mechanism ofgastrin and its antagonists proglumide and somatostatin on coIorectal carcinoma and their clinical significance.METHODS A model of transplanted human colonic carcinoma was established from SW480cell line in gymnomouse body. The volume andweight of transplanted carcinoma was observedunder the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content ot carcinoma cell was determined by redioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viabIe cells was determined by MTT colorimetric analysis, lP3 content was determined by radioimmunoassay, Ca2+ concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc,C-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immunocytochemistry SP method. Argyrophilianucleolar organizer regions was determined withargyrophilia stain.RESULTS The volume, weight, cAMP, DNAand protein content in carcinoma cell, cellamount and proliferation index of S and G2Mphase in PG group were all significantly higher than those of control group. When PG was at theconcentration of 25 mg/ L, the amount of viablecells, lP3 content and Ca2+ concentration in celland membrane PKC activity in PG group weresigniticantly higher than those in control group;when PGL was at a concentration ot 32 mg/L,they dropped to the lowest level in PG (25 mg/L)+ PGL group, but without significant differencefrom the control group. The positive expression rate of gastrin, c-myc, c-fos and rasp21 in carcinoma tissue was 39 .6%, 54 .2%, 47. 9% and54 .2% resPectively and significantly higher than that in mucosa 3 cm and 6 cm adjacent tocarcinoma tissue and normal colorectal mucosa.The positive expression rate of gastrin of highlydifferentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocarcinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3 cm and 6 cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin-negative group.CONCLUSION Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL hasno obvious effect on the growth of human colonic carcinoma SW480 cell line, but couldinhibit the growth-promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directlybut also depress the growth-promoting effect ofgastrin on the transplanted carcinoma. Somecolorectal carcinoma cells can produce and secrete gastrin through autocrine, highly-differentiated adenocarcinoma express the highest level gastrin. Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene omyc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL,somatostatin of patients with colorectalcarcinoma.
基金Project supported by the National Natural Science Foundation of China,No.39670896
文摘AIM To study the role of cholecystokinin octapeptide ( CCK-8), β-endorphin ( β-EP), and gastrin in an anorexic infantile rat model and no subsequent regulation of nose peptides by the Yunpi complex prescription ErBao Granule.METHODS We fed infantile rats with special prepared forage. A liquid extract of ErBao Granule was administered to the rats daily for 3weeks, CCK-8, β-EP, and gastrin concentrations in hypothalamus, gastric antrum, and plasma of the rats were measured by radioimmunoassay,and were compared with controls.RESULTS Treatment of rats with ErBao Granule inhibited CCK-8 secretion and increased β-EP and gastrin secretion. CCK-8 concentration in hypothalamus and plasma of model control group increased significantly and correlated negatively with food intake of models.respectively. β-EP concentration in gastric antrum and plasma of model control group decreased significantly and showed a positive correlation with food intake of models,respectively. Hypothalamus concentration of β-EP was similar in models and controls. Gastrin concentration in gastric antrum of models was lower than in the blank control group, and correlated positively to food intake of models.Finally, CCK-8 concentrations in plasma of rats showed a positive correlation with plasma β-EP(r- 0.68, P＜0.05).CONCLUSION The increased plasma and hypothalamus concentration of CCK-8,decreased gastric antrum and plasma level of β-EP. and decreased gastric antrum concentration of gastrin are associated significantly with the anorexia of infantile anorexic rat models produced by special forage. ErBao Granule can reverse these changes, which may be the major mechanisms of ErBao Granule simulating feeding.
基金Supported by The National Natural Science Foundation of China,No.81072030 and No.81372659Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori(H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2(COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk.
基金a grant from the Science and Technique Foundation of Liaoning Province (No. 9910500707).
文摘BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis. METHODS: The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay. RESULTS: The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01).CONCLUSIONS: The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.
文摘INTRODUCTIONGastrin is atrophic gastrointestinal hormone whichis secreted by G cell.Gastrin has long beenconsidered a growth stimulatory hormone formucosa of the gastrointestinal tract.The growthresponses of certain colorectal cancer cells,andxenografts,can be stimulated by endogenousgastrin.Protein kinase C (PKC) is a family ofisozymes that plays a crucial role in transducingsignals of many hormones,growth peptides,
基金the Youth Scientific Found of Ministry of Healthy.
文摘AIM To investigate the changes of gastricmucosal ascorbic acid secretion in patients withnonulcer dyspepsia and the effect of gastrin onit,and to relate any observed changes to H.pylori infection and mucosal histology.METHODS Ascorbic acid secretions in patientswere examined by collecting continuouslygastric juice for one hour after having aspiratedand discarded fasting gastric juice.Using theclearance rate(mL/min)of ascorbic acid fromblood to gastric juice represented ascorbic acidsecretion in the gastric mucosa.Ascorbic acidconcentrations in plasma and juice weremeasured by ferric reduced method.RESULTS Gastric ascorbic acid secretions inH.pylori-positive patients(1.46 mL/min,range0.27-3.78)did not significantly differ fromthose in H.pylori-negative patients(1.25 mL/min,0.47-3.14)(P】0.05).There were nosignificant differences in ascorbic acidsecretions between patients with mild(1.56 mL/min,0.50-3.30),moderate(1.34 mL/min,0.27-2.93)and severe(1.36 mL/min,0.47-3.78)inflammation(P】0.05).There were nosignificant differences in ascorbic acidsecretions between patients without activity(l.45mL/min,0.27-3.14)and with mild(1.32mL/min,0.61-2.93),moderate(1.49mL/min,0.50-3.78)and severe(1.43 mL/min,0.51-3.26)activity of chronic gastritis either(P】0.05).Ascorbic acid secretions in patientswith severe atrophy(0.56 mL/min,0.27-1.20)were markedly lower than those in patientswithout atrophy(1.51 mL/min,0.59-3.30)and with mild(1.43 mL/ min,0.53-3.78)andmoderate(1.31 mL/min,0.47-3.16)atrophy(P【0.005).There was a significant negativecorrelation between ascorbic acid secretion andseverity of atrophy(correlation coefficient=-0.43,P【0.005).After administration ofpentagastrin,ascorbic acid secretions weremarkedly elevated(from 1.39 mL/min,0.36-2.96 to 3.53mL/min,0.84-5.91)(P【0.001).CONCLUSION Ascorbic acid secretion ingastric mucosa is not affected by H.pyloriinfection.Gastric ascorbic acid secretion ismarkedly related to the severity of atrophy,whereas not related to the severity ofinflammation and activity.Gastrin may stimulategastric ascorbic acid secretion.A decreasedascorbic acid secretion may be an importantfactor in the link between atrophic gastritis andgastric carcinogenesis.
基金Supported by Natural Science Foundation of Anhui Province,No.1408085MH148Natural Science Fund of Education Bureau of Anhui Province,No.kj2010b242+1 种基金Natural Science Fund of Wannan Medical College,No.wk2012zf02the key science and technology project of Wuhu City,No.health-2-4
文摘AIM:To explore the role and mechanisms of extracellular signal-regulated protein kinase-mitogen-activated protein kinase(ERK-MAPK) signaling in pentagastrinregulated growth of large intestinal carcinoma.METHODS:HT-29 cells were incubated in different media and divided into the control group,pentagastrin group,proglumide group,and pentagastrin + proglumide group.No reagent was added to the control group,and other groups were incubated with reagent at different concentrations.Changes in proliferation of HT-29 cells were detected by MTT assay,and the optimal concentrations of pentagastrin and proglumide were determined.The changes in proliferation index(PI) and apoptosis rate(AR) of HT-29 cells were detected by Annexin V-fluorescein isothiocyanate flow cytometry.mRNA expression of pentagastrin receptor/cholecystokinin-B receptor(CCK-BR),ERK1/2 and K-ras were detected by reverse transcriptase polymerase chain reaction.The protein and phosphorylation level of ERK1/2 and K-ras were detected by western blotting.All data were analyzed by analysis of variance and SNK-q test.RESULTS:The proliferation of HT-29 cells was stimulated by pentagastrin at a concentration of 6.25-100 mg/L,and the optimal concentration of pentagastrin was 25.0 mg/L(F = 31.36,P < 0.05).Proglumide had no obvious effect on the proliferation of HT-29 cells,while it significantly inhibited the proliferation of HT-29 cells stimulated by pentagastrin when the concentration of proglumide was 8.0-128.0 mg/L,and the optimal concentration was 32.0 mg/L(F = 24.31,P < 0.05).The PI of the pentagastrin(25.0 mg/L) group was 37.5% ± 5.2%,which was significantly higher than 27.7% ± 5.0% of the control group and 27.3% ± 5.8% of the pentagastrin(25.0 mg/L) + proglumide(32.0 mg/L) group(Q = 4.56-4.75,P < 0.05).The AR of the pentagastrin(25.0 mg/L) group was 1.9% ± 0.4%,which was significantly lower than 2.5% ± 0.4% of the control group and 2.4% ± 0.3% of the pentagastrin(25.0 mg/L) + proglumide(32.0 mg/L) group(Q = 4.23-4.06,P < 0.05).mRNA expression of CCK-BR was detected in HT-29 cells.The phosphorylation levels of ERK1/2 protein and phosphorylated K-ras protein of the pentagastrin group were 0.43% ± 0.04% and 0.45% ± 0.06%,which were significantly higher than 0.32% ± 0.02% and 0.31% ± 0.05% of the control group(Q = 7.78-4.95,P < 0.05),and 0.36% ± 0.01% and 0.35% ± 0.04% of the pentagastrin + proglumide group(Q = 5.72-4.08,P < 0.05).There were no significant differences in the mRNA and protein expression of ERK1/2 and K-ras among the control,pentagastrin,proglumide and pentagastrin + proglumide groups(F = 0.52,0.72,0.78,0.28;P > 0.05).CONCLUSION:Gastrin stimulates proliferation of HT-29 cells and inhibits apoptosis by upregulating phosphorylation of ERK and K-ras through the Ras-Raf-MEK1/2-ERK1/2 pathway,and this is restrained by proglumide.
基金the Second People's Hospital of Anhui Province,Institutional Review Board(Approval No.2015-036).
文摘BACKGROUND Serum gastrin-17(G-17),pepsinogen I(PGI),and pepsinogen II(PGII)concentrations regulate gastric acid secretion,and hypersecretion of gastric acid increases the risks of peptic ulcer and upper gastrointestinal bleeding.These associations suggest that serum G-17,PGI,and(or)PGII may predict gastrointestinal bleeding risk among peptic ulcer patients.AIM To evaluate the efficacies of serum G-17,PGI,PGII,and PGI/PGII ratio(PGR)for predicting upper gastrointestinal bleeding among peptic ulcer patients.METHODS A total of 199 patients diagnosed with peptic ulcer confirmed by gastroscopy and positivity for Helicobacter pylori by the 14C-urea breath test were recruited,including 107 patients with simple peptic ulcer and 92 cases complicated by upper gastrointestinal bleeding.Serum PGI,PGII,G-17,and PGR were measured by immune methods and compared between bleeding and non-bleeding groups by univariate analysis.The specificity and sensitivity of PGs and G-17 for evaluating upper gastrointestinal bleeding risk were then assessed by constructing receiver operating characteristic(ROC)curves.RESULTS Serum G-17 was significantly higher among peptic ulcer patients with upper gastrointestinal bleeding compared to simple peptic ulcer patients(25.34±14.29 vs 8.84±8.03 pmol/L,t=9.822,P<0.01),whereas serum PGI,PGII,and PGR did not differ significantly between bleeding and non-bleeding groups(all P>0.05).The risk of bleeding was significantly higher among peptic ulcer patients with elevated serum G-17(>15 pmol/L)compared to patients with normal or low serum G-17(73.2%vs 27.4%,χ2=40.72,P<0.01).The area under the ROC curve for serum G-17 was 0.866±0.024,and a cut-off of 9.86 pmol/L yielded 90.2%sensitivity and 68.2%specificity for distinguishing peptic ulcer with and without upper gastrointestinal bleeding.CONCLUSION Serum G-17 is significantly upregulated in peptic ulcer patients and higher levels are predictive of upper gastrointestinal bleeding.Conversely,serum PGI,PGII,and PGR have no predictive value.Further prospective studies are warranted to examine if high G-17 can be used to assess risk of bleeding prior to onset.
