AIM: To assess the mechanisms of protective action by different mild irritants through maintenance of gastric mucosal integrity and modulation of mucosal nitric oxide (NO) in experimental gastritis rats.METHODS: Etche...AIM: To assess the mechanisms of protective action by different mild irritants through maintenance of gastric mucosal integrity and modulation of mucosal nitric oxide (NO) in experimental gastritis rats.METHODS: Etcher 200 mL/L ethanol, 50 g/L NaG or 0.3 mol/L HCl was pretreated to normal or 800 mL/L ethanol-induced acute gastritis Sprague-Dawley rats before a subsequent challenge with 500 mL/L ethanol. Both macroscopic lesion areas and histological damage scores were determined in the gastric mucosa of each group of animals. Besides,gastric mucosal activities of NO synthase isoforms and of superoxide dismutase, along with mucosal level of leukotriene (LT)C4 were measured.RESULTS: Macroscopic mucosal damages were protected by 200 mL/L ethanol and 50 g/L NaCI in gastritis rats.However, although 200 mL/L ethanol could protect the surface layers of mucosal cells in normal animals (protection attenuated by NG-nitro-L-arginine methyl ester), no cytoprotection against deeper histological damages was found in gastritis rats. Besides, inducible NO synthase activity was increased in the mucosa of gastritis animals and unaltered by mild irritants. Nevertheless, the elevation in mucosal LTC4 level following 500 mL/L ethanol administration and under gastritis condition was significantly reduced by pretreatment of all three mild irritants in both normal and gastritis animals.CONCLUSION: These findings suggest that the aggravated 500 mL/L ethanol-evoked mucosal damages under gastritis condition could be due to increased inducible NO and LTC4 production in the gastric mucosa. Only 200 mL/L ethanol is truly 'cytoprotective' at the surface glandular level of nongastritis mucosa. Furthermore, the macroscopic protection of the three mild irritants involves reduction of LTC4 level in both normal and gastritis mucosa, implicating preservation of the vasculature.展开更多
AIM: Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins. Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide.Both have constitutive and inducible ...AIM: Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins. Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide.Both have constitutive and inducible isoforms. The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis, tumorigenesis and inflammatory processes. This study was to clarify their role in pancreatic adenocarcinomas.METHODS: We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological data.RESULTS: Twenty-one (52.5%) of the cases showed iNOS expression, 15 (37.5%) of the cases were positive for COX-2.The immunoreaction was heterogeneously distributed within the tumors. Staining intensity was different between the tumors. No correlation between iNOS and COX-2 expression was seen. There was no relationship with microvessel density.However, iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression. There was no correlation with other clinicopathological data.CONCLUSION: Approximately half of the cases expressed iNOS and COX-2. These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas. Due to a low prevalence of COX-2 expression, chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.展开更多
AIM: To determine the role and effect of nitric oxide synthase type Ⅱ (NOSII) in cirrhotic rats.METHODS: Expression of NOSⅡ mRNA was detected by real time RT-PCR. The activity of nitric oxide synthase and serum leve...AIM: To determine the role and effect of nitric oxide synthase type Ⅱ (NOSII) in cirrhotic rats.METHODS: Expression of NOSⅡ mRNA was detected by real time RT-PCR. The activity of nitric oxide synthase and serum levels of NO, systemic and portal hemodynamics and degrees of cirrhosis were measured with high sensitive methods. Chinese traditional medicine tetrandrine was used to treat cirrhotic rats and to evaluate the function of NO.Double-blind method was applied during the experiment.RESULTS: The concentration of NO and the activity of NOS were increased markedly at all stages of cirrhosis, and iNOSmRNA was greatly expressed. Meanwhile the portalvenous-pressure (PVP), and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the quantity of hepatic fibrosis.Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA.CONCLUSION: Increased hepatic expression of NOSII is one of the important causes of hepatic cirrhosis and portal hypertension.展开更多
AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE...AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastrointestinal functions of endotoxin-treated mice.METHODS: Diarrheogic activity, GIT, and intestinal fluid content as well as nitric oxide and PGE2 products were measured after intraperitoneal administration of LPS in mice.RESULTS: LPS dose-dependently accumulated abundant fluid into the small intestine, induced diarrhea, but decreased the GIT. Both nitric oxide and PGE2 were found to increase in LPS-treated mice. Western blot analysis indicated that LPS significantly induced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in mice intestines. Pretreatment with NG-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis) significantly attenuated the effects of LPS on the diarrheogenic activity and intestine content, but reversed the GIT.CONCLUSION: The present study suggests that the pathogenesis of LPS treatment may mediate the stimulatory effect of LPS on nitric oxide and PGE2 production and NO/prostaglandin pathway may play an important role on gastrointestinal function.展开更多
AIM:To determine the role of mucosal gene expression of cyclooxygenase 2 (COX-2), pS2 (belongs to trefoil peptides),inducible nitric oxide synthase (iNOS) and transforminggro wth factor alpha (TGFα in gastric adaptat...AIM:To determine the role of mucosal gene expression of cyclooxygenase 2 (COX-2), pS2 (belongs to trefoil peptides),inducible nitric oxide synthase (iNOS) and transforminggro wth factor alpha (TGFα in gastric adaptation to water immersion and restraint stress (WRS) in rats.METHODS: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 d. Gastric mucosal blood flow (GMBF-) was measured by laser Doppler flowmeter3. The extent of gastric mucosal lesions were evaluated grossly and histologically and expressions of COX-2, pS2,iNOS and TGFα were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot.RESULTS: The damage to the surface of gastric epithelium with focal areas of deep haemorrhagic necrosis was induced by repeated WRS.The adaptative cytoprotection against stress was developed with activation of cell proliferation in the neck regions of gastric glands. The ulcer index (UI) in groups Ⅱ, Ⅲ and IV was markedly reduced as compared with group Ⅰ (Ⅰ: 47.23±1.20; Ⅳ: 10.39±1.18,P<0.01). GMBF significantly decreased after first exposure to WRS with an adaptive increasement of GMBF in experimental groups after repetitive challenges with WRS. After the 4th WRS,the value of GMBF almost restored to normal level (Ⅰ: 321.87±8.85; Ⅳ: 455.95±11.81,P<0.01). First WRS significantly decreased the expression of pS2 and significantly increased the expressions of COX-2, iNOS and TGFα After repeated WRS, pS2 and TGFα expressions gradually increased (pS2: Ⅰ: 0.37±0.02; Ⅳ: 0.77±0.01; TGFα Ⅰ: 0.86±0.01, Ⅳ: 0.93±0.03, P<0.05) with a decrease in the expressions of COX-2 and iNOS (COX-2: Ⅰ: 0.45±0.02; Ⅳ:0.22±0.01; iNOS: Ⅰ: 0.93±0.01; Ⅳ: 0.56±0.01, P<0.01).Expressions of pS2, COX-2, iNOS and TGFα showed regular changes with a good relationship among them.CONCLUSION: Gastric adaptation to WRS injury involves enhanced cell proliferation,increased expression of pS2 and TGFα, and reduced expression of COX-2 and iNOS.These changes play an important role in adaptation of gastric mucosa after repeated WRS.展开更多
Forty-eight New Zealand rabbits were divided into normal group (n=18), control group (n=18) and Chinese herbs treatment group (n=12) randomly. The rabbits in the normal group received sham-operation, and the OA model ...Forty-eight New Zealand rabbits were divided into normal group (n=18), control group (n=18) and Chinese herbs treatment group (n=12) randomly. The rabbits in the normal group received sham-operation, and the OA model was established by Hulth's method. All the rabbits in the treatment group were given Bushen Huoxue Decoction (补肾活血汤) from the 6th week after the operation. At 6th, 8th and 12th week after the operation, the NO concentrations of the serum, joint cartilage and synovium were examined. Results: Indicated that the NO concentrations of the serum,joint cartilage and synovium in the control group were all significantly higher than those in the normal group, with the joint cartilage more obvious (P<0.05). In the Chinese herbs treatment group the NO concentrations in all the parts obviously decreased as compared with the control group (P<0.05). It is suggested that Bushen Huoxue Decoction decrease the levels of NO in the serum, synovium and joint cartilage in the OA rabbit.展开更多
AIM: To determine whether Saiko-keishioto (TJ-10), a Japanese herbal medicine, could protect liver injury induced by gut ischemia/reperfusion (I/R), and to investigate the role of NO.METHODS: Male Wistar rats were exp...AIM: To determine whether Saiko-keishioto (TJ-10), a Japanese herbal medicine, could protect liver injury induced by gut ischemia/reperfusion (I/R), and to investigate the role of NO.METHODS: Male Wistar rats were exposed to 30-min gut ischemia followed by 60 min of reperfusion. Intravital microscopywas used to monitor leukocyte recruitment. Plasma tumor necrosis factor (TNF) levels and alanine aminotransferase (ALT) activities were measured. T]-10 1 gl(kg.d) was intragastrically administered to rats for 7 d. A NO synthase inhibitor was administered.RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF levels and ALT activities were mitigated by pretreatment withT]-10. Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver, and the increase of plasma TNF levels and ALT activities. Pretreatment with TL-10 increased plasma nitrite/nitrate levels.CONCLUSION: TJ-10 attenuates the gut I/R-induced hepalJc microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.展开更多
To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to...To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis. Sermn NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol. The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Resu/ts.Cholesterol diet significantly increased sermn levels of cholesterol and LDL, caused a remarkable platelet hyperaggregability, and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination. The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNIP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclexosis. :The present study suggests that the endothelial dysfunction caused by enhanced sermn cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.展开更多
文摘AIM: To assess the mechanisms of protective action by different mild irritants through maintenance of gastric mucosal integrity and modulation of mucosal nitric oxide (NO) in experimental gastritis rats.METHODS: Etcher 200 mL/L ethanol, 50 g/L NaG or 0.3 mol/L HCl was pretreated to normal or 800 mL/L ethanol-induced acute gastritis Sprague-Dawley rats before a subsequent challenge with 500 mL/L ethanol. Both macroscopic lesion areas and histological damage scores were determined in the gastric mucosa of each group of animals. Besides,gastric mucosal activities of NO synthase isoforms and of superoxide dismutase, along with mucosal level of leukotriene (LT)C4 were measured.RESULTS: Macroscopic mucosal damages were protected by 200 mL/L ethanol and 50 g/L NaCI in gastritis rats.However, although 200 mL/L ethanol could protect the surface layers of mucosal cells in normal animals (protection attenuated by NG-nitro-L-arginine methyl ester), no cytoprotection against deeper histological damages was found in gastritis rats. Besides, inducible NO synthase activity was increased in the mucosa of gastritis animals and unaltered by mild irritants. Nevertheless, the elevation in mucosal LTC4 level following 500 mL/L ethanol administration and under gastritis condition was significantly reduced by pretreatment of all three mild irritants in both normal and gastritis animals.CONCLUSION: These findings suggest that the aggravated 500 mL/L ethanol-evoked mucosal damages under gastritis condition could be due to increased inducible NO and LTC4 production in the gastric mucosa. Only 200 mL/L ethanol is truly 'cytoprotective' at the surface glandular level of nongastritis mucosa. Furthermore, the macroscopic protection of the three mild irritants involves reduction of LTC4 level in both normal and gastritis mucosa, implicating preservation of the vasculature.
文摘AIM: Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins. Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide.Both have constitutive and inducible isoforms. The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis, tumorigenesis and inflammatory processes. This study was to clarify their role in pancreatic adenocarcinomas.METHODS: We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological data.RESULTS: Twenty-one (52.5%) of the cases showed iNOS expression, 15 (37.5%) of the cases were positive for COX-2.The immunoreaction was heterogeneously distributed within the tumors. Staining intensity was different between the tumors. No correlation between iNOS and COX-2 expression was seen. There was no relationship with microvessel density.However, iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression. There was no correlation with other clinicopathological data.CONCLUSION: Approximately half of the cases expressed iNOS and COX-2. These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas. Due to a low prevalence of COX-2 expression, chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.
文摘AIM: To determine the role and effect of nitric oxide synthase type Ⅱ (NOSII) in cirrhotic rats.METHODS: Expression of NOSⅡ mRNA was detected by real time RT-PCR. The activity of nitric oxide synthase and serum levels of NO, systemic and portal hemodynamics and degrees of cirrhosis were measured with high sensitive methods. Chinese traditional medicine tetrandrine was used to treat cirrhotic rats and to evaluate the function of NO.Double-blind method was applied during the experiment.RESULTS: The concentration of NO and the activity of NOS were increased markedly at all stages of cirrhosis, and iNOSmRNA was greatly expressed. Meanwhile the portalvenous-pressure (PVP), and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the quantity of hepatic fibrosis.Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA.CONCLUSION: Increased hepatic expression of NOSII is one of the important causes of hepatic cirrhosis and portal hypertension.
基金Supported by the National Science Council of Taiwan (NSC 92-2320-B-038-027) the Min-Sheng Healthcare (93MSH-TMU-006)
文摘AIM: To investigate the effect of lipopolysaccharide (LPS)on the diarrheogenic activity, gastrointestinal transit (GIT),and intestinal fluid content and the possible role of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastrointestinal functions of endotoxin-treated mice.METHODS: Diarrheogic activity, GIT, and intestinal fluid content as well as nitric oxide and PGE2 products were measured after intraperitoneal administration of LPS in mice.RESULTS: LPS dose-dependently accumulated abundant fluid into the small intestine, induced diarrhea, but decreased the GIT. Both nitric oxide and PGE2 were found to increase in LPS-treated mice. Western blot analysis indicated that LPS significantly induced the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 in mice intestines. Pretreatment with NG-nitro-L-arginine-methyl ester (L-NAME, a non-selective NOS inhibitor) or indomethacin (an inhibitor of prostaglandin synthesis) significantly attenuated the effects of LPS on the diarrheogenic activity and intestine content, but reversed the GIT.CONCLUSION: The present study suggests that the pathogenesis of LPS treatment may mediate the stimulatory effect of LPS on nitric oxide and PGE2 production and NO/prostaglandin pathway may play an important role on gastrointestinal function.
文摘AIM:To determine the role of mucosal gene expression of cyclooxygenase 2 (COX-2), pS2 (belongs to trefoil peptides),inducible nitric oxide synthase (iNOS) and transforminggro wth factor alpha (TGFα in gastric adaptation to water immersion and restraint stress (WRS) in rats.METHODS: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 d. Gastric mucosal blood flow (GMBF-) was measured by laser Doppler flowmeter3. The extent of gastric mucosal lesions were evaluated grossly and histologically and expressions of COX-2, pS2,iNOS and TGFα were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot.RESULTS: The damage to the surface of gastric epithelium with focal areas of deep haemorrhagic necrosis was induced by repeated WRS.The adaptative cytoprotection against stress was developed with activation of cell proliferation in the neck regions of gastric glands. The ulcer index (UI) in groups Ⅱ, Ⅲ and IV was markedly reduced as compared with group Ⅰ (Ⅰ: 47.23±1.20; Ⅳ: 10.39±1.18,P<0.01). GMBF significantly decreased after first exposure to WRS with an adaptive increasement of GMBF in experimental groups after repetitive challenges with WRS. After the 4th WRS,the value of GMBF almost restored to normal level (Ⅰ: 321.87±8.85; Ⅳ: 455.95±11.81,P<0.01). First WRS significantly decreased the expression of pS2 and significantly increased the expressions of COX-2, iNOS and TGFα After repeated WRS, pS2 and TGFα expressions gradually increased (pS2: Ⅰ: 0.37±0.02; Ⅳ: 0.77±0.01; TGFα Ⅰ: 0.86±0.01, Ⅳ: 0.93±0.03, P<0.05) with a decrease in the expressions of COX-2 and iNOS (COX-2: Ⅰ: 0.45±0.02; Ⅳ:0.22±0.01; iNOS: Ⅰ: 0.93±0.01; Ⅳ: 0.56±0.01, P<0.01).Expressions of pS2, COX-2, iNOS and TGFα showed regular changes with a good relationship among them.CONCLUSION: Gastric adaptation to WRS injury involves enhanced cell proliferation,increased expression of pS2 and TGFα, and reduced expression of COX-2 and iNOS.These changes play an important role in adaptation of gastric mucosa after repeated WRS.
文摘Forty-eight New Zealand rabbits were divided into normal group (n=18), control group (n=18) and Chinese herbs treatment group (n=12) randomly. The rabbits in the normal group received sham-operation, and the OA model was established by Hulth's method. All the rabbits in the treatment group were given Bushen Huoxue Decoction (补肾活血汤) from the 6th week after the operation. At 6th, 8th and 12th week after the operation, the NO concentrations of the serum, joint cartilage and synovium were examined. Results: Indicated that the NO concentrations of the serum,joint cartilage and synovium in the control group were all significantly higher than those in the normal group, with the joint cartilage more obvious (P<0.05). In the Chinese herbs treatment group the NO concentrations in all the parts obviously decreased as compared with the control group (P<0.05). It is suggested that Bushen Huoxue Decoction decrease the levels of NO in the serum, synovium and joint cartilage in the OA rabbit.
文摘AIM: To determine whether Saiko-keishioto (TJ-10), a Japanese herbal medicine, could protect liver injury induced by gut ischemia/reperfusion (I/R), and to investigate the role of NO.METHODS: Male Wistar rats were exposed to 30-min gut ischemia followed by 60 min of reperfusion. Intravital microscopywas used to monitor leukocyte recruitment. Plasma tumor necrosis factor (TNF) levels and alanine aminotransferase (ALT) activities were measured. T]-10 1 gl(kg.d) was intragastrically administered to rats for 7 d. A NO synthase inhibitor was administered.RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF levels and ALT activities were mitigated by pretreatment withT]-10. Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver, and the increase of plasma TNF levels and ALT activities. Pretreatment with TL-10 increased plasma nitrite/nitrate levels.CONCLUSION: TJ-10 attenuates the gut I/R-induced hepalJc microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.
文摘To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis. Sermn NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol. The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Resu/ts.Cholesterol diet significantly increased sermn levels of cholesterol and LDL, caused a remarkable platelet hyperaggregability, and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination. The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNIP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclexosis. :The present study suggests that the endothelial dysfunction caused by enhanced sermn cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.
