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Objective: To investigate the effect of COX-2 inhibitor bevacizumab on the activity and apoptosis of retinal ganglion RGC-5 cells induced by H2O2 and the regulation of p38 MAPK signaling pathway. Methods: Retinal ganglion RGC-5 cells was stimulated using H2O2 ( 200, 300, 400, 600, 800 μmol/L) to establish a H2O2 damage model, H2O2 concentration was selected based on half inhibitory concentration, COX-2 inhibitor bevacizumab treated RGC-5 cell induced by H2O2 for 7 h, SB203580 as a p38 MAPK signaling pathway inhibitor, cell viability and apoptosis rate were detected by MTT method and flow cytometry, respectively; the expression of PCNA, p53, p38 and p-p38 protein were detected by Western blot. Results: Different concentrations of H2O2 could inhibit the viability of RGC-5 cells, and the cell viability decreased with the increase of H2O2 concentration, because 400 μmol/L H2O2 inhibited half of the cell viability, it was selected as an object of study. Compared with the control group, the cell viability and the expression of PCNA were decreased significantly in H2O2 group, the apoptosis rate and the expression of p53 and p-p38 protein was increased significantly; compared with H2O2 group, the cell viability and PCNA expression were increased significantly in the H2O2+bevacizumab group, the apoptosis rate and the expression of p53 and p-p38 protein were decreased significantly ( P ＜ 0. 05); compared with H2O2+ bevacizumab group, the cell viability and PCNA expression were increased significantly in H2O2+bevacizumab+SB203580 group, the apoptosis rate and the expression of p53 and p-p38 protein were decreased significantly ( P＜0. 05). Conclusion: Inhibition of immunosuppressive factor COX-2 expression can improve the activity of retinal ganglion cells and inhibit apoptosis by regulating the p38 MAPK signaling pathway.
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Objective To investigate the effect of docosahexaenoic acid (DHA) combined with cyclooxygenase-2 (COX-2) selective inhibitor NS-398 on the apoptosis of cholangiocarcinoma QBC939 cells and the mechanism.Methods In vitro,cholangiocarcinoma QBC939 cells were treated with 0,15,30,45,60 and 75 μg/ml DHA with 0,25,50,100,150 and 200 μmol/L NS-398,respectively.The absorbances of the QBC939 cells were measured by CCK8 and its growth inhibition ratios were analyzed.Flow cytometry was applied to detect cell apoptosis.The level of β-catenin and COX-2 mRNA and protein were measured by real-time PCR,immunocytochemistry and enzyme-linked immunoadsordent assay,respectively.Results DHA combined with NS-398 could significantly suppress the growth of QBC939 cells (P ＜ 0.05).When the concentration of DHA went up to 45 μg/ml and NS-398 was 100 μmol/L,the relative growth inhibition rate of QBC939 cells was 90.0％.If the concentrations were increased,the result showed no significant differences.Furthermore,flow cytometry analysis indicated that DHA combined with NS-398 could induce QBC939 cells apoptosis at the early stage,and the apoptosis rate was significantly different between the experimental and control groups (P ＜ 0.01).Real-time PCR showed low β-catenin and COX-2 expression in QBC939 cells disposed by DHA combined with NS-398,and their expression were significantly different between the experimental and control groups (P ＜ 0.01).Immunocytochemistry and ELISA demonstrated that DHA combined with NS-398 could decrease β-catenin and COX-2 protein expression in QBC939 cells.Conclusion DHA combined with NS-398 induced apoptosis and inhibited proliferation of cholangiocarcinoma cells QBC939 in vitro through targeting β-catenin and COX-2.
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Objective To study the radiation sensitive enhancement ratio (SER) of NS398 on esophageal cancer stem cells and adherent tumor cells and analyze the radioresistance related protein expressions.Methods ECA109 esophageal cancer stem cells were cultured in serum-free medium.Expression levels of cell surface maker CD44 + and CD271 + were analyzed by flow cytometry.MTT assay was used to detect cell proliferation after the treatments with NS398 and irradiation(0,4 and 8 Gy).The sensitization effects of NS398 on the parental cells and its spheroid were evaluated by clone formation assay.Western blot assay was performed to determine protein expressions.Results Serum-free medium was successfully applied to isolate the cancer stem cells with spherical properties.CD271 + in the spheroid cells was notable higher than that in the parent cells (t =3.81,P ＜ 0.05).After irradiation,the proliferation rate of parental cells was higher than that in spheroid cells.After the combination treatment of NS398 and irradiation,SF2 value of parental cells was lower than spheroid cells(t =2.91,P ＜ 0.05)and the SER of NS398 on parental cells was greater than spheroid cells.The expressions of Bmi-1,c-Myc,β-catenin and Cyclin D1 in spheroid cells were higher than those in parental cells (t =8.09,7.90,7.50,7.15,P＜0.05).Cyclin D1 expression levels under both cell situations increased after 4 Gy irradiation (t =9.74,6.67,P ＜0.05).Compared to the 4 Gy irradiation alone group,the β-catenin and Cyclin D1 expression levels in both parental cells (t =10.15,12.12,P ＜ 0.05) and spheroid cells (t =3.23,7.45,P ＜ 0.05) decreased in the combination group.Conclusions Esophageal cancer stem cells with high level of CD271 can be isolated with serum-free medium and it is radioresistant where β-catenin and its downstream proteins may be involved.
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Objective To study the effect of selective COX-2 inhibitor NS398 on IL-10 and IFN-γexpression in human keratinocytes induced by UVA,and further to explore the effect on anti human skin photoaging.Methods HaCaT cells were divided into three groups:simple UV exposure group,NS398-intervene group and blank group.For UV radiation,simple UV exposure group and NS398-intervene group were irradiated with UVA at a dose of 30 J/cm2.In order to assess the effect of NS398,HaCat cells were treated with NS398 at the dose of 0,20,40,80μmol/L respectively and then incubated without irradiation for 2h,substrate changed and cultured for 24h,and then the expression of IL-10 and IFN-γ mRNA was detected via RT-PCR.Results Simple UV exposure group had obviously higher expression of IL-10 mRNA and lower expression of IFN-γ mRNA than that of control group,while NS398-intervened group had significantly lower expression of IL-10 mRNA and higher expression of IFN-γ mRNA than that of simple UV exposure group,and dose-dependency existed.Conclusions NS398 may delay photo-damage of human skin via inhibiting the expression of IL-10 mRNA and up-regulating the expression of IFN-γ mRNA in human keractinocytes.
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Objective To study the effect of selective COX-2 inhibitor NS-398 on IL-1α and TNF a expression in HaCaT cells induced by UVA/UVB,and further to explore the mechanism on anti human skin photo damage. Methods The subcuhured HaCaT cells were divided into three groups:simple illuminated group was exposed to UVA/UVB directly,NS-398 interfered group was exposed to UVA/UVB after being treated with NS-398 in different concentrations,and the control group was cultured in normal without any treatment.The expression of IL -1α and TNF-α in supernarant was detected by ELISA kit.Results The level of IL-1α and TNF-α expression in supernatant from simple illuminated group was remarkably higher than that in the control group,NS-398 interfered group showed much lower level than the simple illuminated one,and the expression of IL-1α and TNF-α was dependent on the concentration of NS-398.Conclusions NS-398 can reduce IL-1α and TNF-α expression in HaCaT cells induced by ultraviolet rays,suggesting the possibility of anti human skin photo- damage effect.
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Objective:To investigate the effect and elucidate the mechanism of the selective cyclooxygenase-2(COX-2)inhibitor NS-398 on apoptosis and survivin, XIAP and c-IAP1 expressions of hepatocarcinoma cell lines. Methods:The proliferation of hepatocarcinoma BEL-7402 cells treated with NS-298 at different concentrations were evaluated by MTT assay. The apoptosis was detected by flow cytometry (FCM) and TUNEL assay. Expressions of COX-2, survivin, XIAP and c-IAP1 were analyzed by immunocytochemical staining. Results: NS-398 significantly inhibited cell proliferation of BEL-7402 cells and induced apoptosis. Immunocytochemisty indicated that the expressions of COX-2, survivin, XIAP and c-IAP1 were significantly down-regulated in BEL-7402 cells by NS-398 treatment compared with untreatment group (P<0.01). Conclusion:NS-398 inhibits the proliferation and induced apoptosis of BEL-7402 cells. The mechanism may be related with down-regulation of the survivin, XIAP and c-IAP1 expression.
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Objective To investigate photo-protective effect of NS398 on above cells damaged from UV irradiation.Methods HaCaT cell and HaCaT keratinocytes were incubated in the culture medium supplemented with different concentration of NS398 for 2h before diffierent dosages of UV irradiation.MTT assay was used to detect cell proliferation and cellular activity:Fluorospectrophotometer assay was used to measure the change of ROS level in the cells which were UV-mediated.Resuits After irradiation with UV,proliferation and cellular activity of HaCaT cells were decreased(P＜0.05);NS398 reduced the generation of ROS in cells induced by UV irradiation apparently and the cell apoptotic rate was dependent on the concentration of NS398. Conclusion NS398 might play an important role in the treatment of UV irradiation injury by decreasing the generation 0f ROS in cells after UV irradiation and increasing the survival ability of HaCaT cells.
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0bjective:To study the proliferative and apoptotic effects of NS398,a selective COX-2 inhibitor,on renal carcinoma cell line 786-O in vitro. Methods:786-O cells were treated with different concentrations of NS398 for24,48,72 and 96 h.The proliferation of 786-O cells was studied by MTT assay.Immuno cytochemistry was used to detect the expressions of COX-2 . The expression of COX-2 mRNA was analyzed by reverse transcription-polymerase chain raction(RT-PCR).Flow cytometric analysis was used to detect the apoptosis status of 786-O cells. Results:NS398 resulted in significant antiproliferative effects on 786-O cells in dose and time dependent manner. Immunocytochemistry showed the expressions of COX-2 were significantly inhibited by NS398. RT-PCR showed the expressions of COX-2 were significantly inhibited by NS398. Apoptosis rate were 31.5%?2.1% and 14.3%?1.4%,respectively in the 786-O cells treated with NS398 in different concentrations of 180 ?umol/L and 30 ?mol/L,which was significantly higher than in the control group 2.1%?0.4%. Conclusion:NS398 could effectively suppress the growth of 786-O cells and induce apoptosis,the mechanism of which probably relates to its inhabited expression of COX-2.
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Objective To explore the role of NS-398 on MVD and VEGF、MMP-9 expression of hepatocullar carcinoma.Methods VEGF and MMP-9 expressions were detected by RT-PCR and flow cytometry.Microvascular density of xenograft tissue were detected by immunohistochemical staining and the serum PGE_(2) was detected by ELISA.Results The expression of VEGF and MMP-9 was significantly downregulated in SMMC-7721 cells exposed to(NS-398) in a dose-dependence and time-dependent manner(P
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PURPOSE: Selective cyclooxygenase (COX)-2 inhibitors have been reported to inhibit cancer cell proliferation. We investigated the effects of NS-398, a selective COX-2 inhibitor, on cell proliferation in human pancreatic cancer cell lines. METHODS: Human pancreatic cancer cell lines, Aspc-1, Capan-1, and Capan-2 were used. We used western blot and/or RT-PCR to evaluate COX-2 and vascular endothelial growth factor expression. Antiproliferative effects were measured by MTT assay, apoptosis assay and cell cycle analysis. Epidermal growth factor (EGF) and troglitazone were used for combined treatment. RESULTS: COX-2 was relatively overexpressed in Capan-1 and Capan- 2, but minimal in Aspc-1 cell line. COX-2 mRNA expression was upregulated by 50 microM of NS-398 in Aspc-1 cell line but was downregulated at 100 microM in all cell lines. Treatment with NS-398 increased cell population of G0/G1 phase and also induced early apoptotic changes in a dose-dependent manner in all three cell lines. Combined treatment with EGF or troglitazone did not seem to affect antiproliferative effects of NS-398. All three cell lines expressed vascular endothelial growth factor constitutively and its expression was downregulated by treatment with NS-398. Pretreatment with NS-398 prior to radiation exposure increased radiosensitivity in Capan-2 cells. CONCLUSION: COX-2 expression was variable in pancreatic cancer cell lines. NS-398 inhibited pancreatic cancer cell proliferation by inducing apoptosis and cell cycle arrest in a dose-dependent manner. Treatment with NS-398 also inhibited expression of VEGF and enhanced radiosensitivity in pancreatic cancer cell lines. COX-2 inhibitors might be promising potential therapeutic agents for patients with pancreatic cancer.
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Humans , Apoptosis , Blotting, Western , Cell Cycle , Cell Cycle Checkpoints , Cell Line , Cell Proliferation , Cyclooxygenase 2 Inhibitors , Cyclooxygenase 2 , Epidermal Growth Factor , Pancreatic Neoplasms , Prostaglandin-Endoperoxide Synthases , Radiation Tolerance , RNA, Messenger , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND: Secondary spinal cord injury (SCI) that follows an initial mechanical insult can exacerbate the overall damage, limit the restorative processes and eventually lead to an in- creased neurological deficit. We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2) may decrease the delayed cell death, and so this will contribute to decreased level of the secondary injury. METHODS: The dorsal surface of the cord at the T9 level was subjected to weight drop impact using a 10 g rod. To block COX-2 activation, a selective COX-2 inhibitor (NS-398) was administered (5 mg/kg, i.p.) 15 min prior to SCI. The COX-1, COX-2, Caspase-3 and PGE2 expressions were measured by real time quantitative RT-PCR and fluorescence immunostaining. RESULTS: Many activated caspase-3 positive cells were observed at 6 h and they increased until 72 h after SCI. The expression of COX-2 peaked at 6 h after SCI, while the COX-1 expression was unaffected. The principal cells that showed a COX-2 expression were the neurons and microglia. Pretreatment with NS-398 caused a significant decrease in the expression of prostaglandin E2 and activated caspase-3 positive cells after SCI. CONCLUSION: These data suggest that COX-2 is one of the main factors related with the pathologic deficits from secondary SCI.
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Animals , Rats , Caspase 3 , Cell Death , Contusions , Cyclooxygenase 2 Inhibitors , Cyclooxygenase 2 , Dinoprostone , Fluorescence , Microglia , Neurons , Spinal Cord Injuries , Spinal CordABSTRACT
BACKGROUND: The facilitatory effect of spinal prostaglandins (PGs) on nociceptive transmission suggests that early PG synthesis after nerve injury could be important in the development of allodynia. METHODS: The aim of this study is to examine the effects of diclofenac (nonselective COX inhibitor), SC-560 (selective COX-1 inhibitor), and NS-398 (selective COX-2 inhibitor) on mechanical allodynia and thermal hyperalgesia in the neuropathic pain model. The rats underwent right L5 spinal nerve ligation (SNL) and were assigned to three COX inhibitor groups to be injected intraperitoneally with different administration dosages (0.2 mg, 1 mg, 5 mg) 30 minutes before, and at 1, 2, and 3 days after SNL. The withdrawal threshold of both hindpaws in response to mechanical stimulation was measured by dynamic plantar anesthesiometer and the withdrawal ratio of right to left hindpaw was calculated. The thermal stimulation applied to both hindpaws by the plantar test was calculated different administration dosages were compared with the vehicle group. RESULTS: There were no differences in mechanical allodynia among the lower dosage groups (0.2 mg) until 14 days after SNL. However, 1 mg of NS-398 decreased mechanical allodynia compared with the vehicle group at 14 days after SNL, and 5 mg of NS-398 decreased mechanical allodynia at 3 days after SNL. However, there was no difference in thermal hyperalgesia between the groups. CONCLUSIONS: These results suggest that intraperitoneal administration of COX inhibitor (especially selective COX-2 inhibitor) after nerve ligation injury can attenuate the development of mechanical allodynia.
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Animals , Rats , Cyclooxygenase Inhibitors , Diclofenac , Hyperalgesia , Ligation , Neuralgia , Prostaglandin-Endoperoxide Synthases , Prostaglandins , Spinal NervesABSTRACT
PURPOSE: NS398, a selective COX-2 inhibitor, is known to inhibit the growth of COX-2 expressing hepatocellular carcinoma cells. The present study investigated whether the cytotoxic effect of NS398 was COX-2 dependent and whether caspases were involved in NS398-induced apoptosis in hepatocellular carcinoma cells. MATERIALS AND METHODS: The expressions of COX-2 in SNU 423 and SNU 449 hepatocellular carcinoma cell lines were examined using RT-PCR and Western blot. The cytotoxic effect of NS398 was measured using MTT in the presence or absence of caspase inhibitors. The distribution of the cell cycle and extent of apoptosis were analyzed using flow cytometry and a Cell Death Elisa kit, respectively. RESULTS: The expression of COX-2 was observed in SNU423 cells, but not in SNU 449 cells. NS398 treatment resulted in both dose-and time-dependent growth inhibitions, with increases in apoptotic cells in both cell lines. Treatment with the pan-caspase inhibitor, z-VAD- fmk, or the caspase-3 inhibitor, Ac-DMQD-CHO, showed no attenuation of the cytotoxic effect of NS398 in either cell line. CONCLUSIONS: This study demonstrated that the cytotoxic effect of NS398 was independent of COX-2 expression. Caspases were also shown not to be involved in NS398-induced apoptosis in either SNU 423 or SNU 449 Korean HCC cell lines. Our data suggests the feasibility of preventing hepatocellular carcinoma with the use of COX-2 inhibitors needs to be carefully evaluated.
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Apoptosis , Blotting, Western , Carcinoma, Hepatocellular , Caspase 3 , Caspase Inhibitors , Caspases , Cell Cycle , Cell Death , Cell Line , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Enzyme-Linked Immunosorbent Assay , Flow CytometryABSTRACT
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are generally attributed to suppression cyclooxygenase enzymes, leading to decreased products of the arachidonic acid cascade. Since the discovery of two isoenzymes of cyclooxygenase, inhibition of cyclooxygenase-2 has been suggested to be responsible for therapeutic effects of NSAIDs without side effects. In the present study, to investigate the extent to peripheral nociception and inflammation of cyclooxygenase-1 and cyclooxygenase-2, diclofenac (non-selective inhibitor), SC-560 (selective cyclooxygenase-1 inhibitor) and NS-398 (selective cyclooxygenase-2 inhibitor) are injected intra-articularly on acute arthritic model in rats. METHODS: Arthritis was induced with 2% lamda-carrageenan (suspended in 50microliter normal saline) into the right knee joint cavity under enflurane anesthesia (2-4%). Before and after the injection, rats were allowed to walk freely through a pathway constructed to record weight load by means of 8 weight sensors (strain gauge type) attached to 8 plates which function independently. The weight load, diameter of both knee joints and weight of rat were measured at each test. At 4 hours and 30 minutes, diclofenac, SC-560 and NS-398 dissolved in 10% dimethyl sulfoxide were injected intra-articularly (50microgram/50microliter). RESULTS: The weight loads increased in diclofenac group at 6 and 9 hours and in NS-398 group at 24 and 48 hours after induction of arthritis. The diameter ratio decreased in diclofenac group at 12 hours after induction of arthritis. CONCLUSIONS: These results suggest that peripheral nociception and inflammation in acute model of arthritis in rats are likely related with both cyclooxygenase-1 and cyclooxygenase-2 pathways.
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Animals , Rats , Anesthesia , Anti-Inflammatory Agents, Non-Steroidal , Arachidonic Acid , Arthritis , Cyclooxygenase 1 , Cyclooxygenase 2 , Diclofenac , Dimethyl Sulfoxide , Enflurane , Inflammation , Isoenzymes , Knee Joint , Nociception , Prostaglandin-Endoperoxide SynthasesABSTRACT
BACKGROUND: Theoretically, an NSAID that inhibits COX-2 selectively should decrease inflammation but not influence normal physiologic functions and thus should cause fewer side effects. In the present study, to investigate the extent of peripheral nociception and inflammation of COX-1 and COX-2, diclofenac (non-selective COX inhibitor), SC-560 (selective COX-1 inhibitor) and NS-398 (selective COX-2 inhibitor) were injected intra-articularly on acute arthritic model in rats and COX-1 and COX-2 mRNA expression were measured by reverse transcription polymerase chain reaction (RT-PCR). METHODS: Arthritis was induced with 2% lambda-carrageenan into the right knee joint cavity under enflurane anesthesia (2-4%). Four and a half hours after the carrageenan injection, diclofenac, SC-560 or NS-398 was injected intra-articularly. The weight loads, diameters of knee joints and body weights were measured. The expressions of COX-1 and COX-2 were investigated in the inflammatory control group by RT-PCR. RESULTS: The weight loads predominantly increased and the diameters of the knee joints decreased in the diclofenac group, but not in the SC-560 and NS-398 groups. After the induction of arthritis, COX-1 and COX-2 mRNA expression increased with peak response at 9 and 6 hours after the induction, respectively. CONCLUSIONS: These results suggested that the non-selective COX inhibitor, diclofenac, which was injected intra-articularly, showed effective analgesic and anti-inflammatory effects in acute arthritic rats, and that the expressions of COX-1 and COX-2 mRNA were increased after induction of arthritis.
Subject(s)
Animals , Rats , Anesthesia , Anti-Inflammatory Agents, Non-Steroidal , Arthritis , Body Weight , Carrageenan , Cyclooxygenase 1 , Cyclooxygenase 2 , Diclofenac , Enflurane , Inflammation , Knee Joint , Nociception , Polymerase Chain Reaction , Prostaglandin-Endoperoxide Synthases , Reverse Transcription , RNA, MessengerABSTRACT
Objective To study the function of cyclooxygenase 2(COX 2) and its specific inhibitor NS 398 on the cell growth and invasion ability of urothelial carcinoma cell line EJ. Methods The cox 2 cDNA was transfected into the urothelial carcinoma cell line EJ and a cell line EJ COX 2 which highly expressed cox 2 gene permanently was gained. The cell growth rate before and after transfection was observed. Then at various concentrations of NS 398, the invasion ability was detected by Boyden Chamber and expression levels of uPA by RT PCR and Western blot. Results The EJ COX 2 cell line grew more rapidly and had a stronger invasion ability than EJ and its uPA expression increased significantly. NS 398 could dose dependently inhibit the expressions of COX 2 and uPA and the invasiveness of EJ COX 2 cell. Conclusion COX 2 can stimulate the growth of urothelial cell line EJ and promote its invasion ability by stimulating the expression of uPA.
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Aim To investigate the effect of selective cyclooxygenase-2 inhibitor, NS-398, on cell apoptosis in leukemia cell line K562 cells and its underlying mechanism. Methods Apoptotic cell percentage was examined by flow cytometry(FCM). The protein expression of Bcl-2 and Caspase-3 was detected by Western blot, and the activity of Caspase-3 was checked by FCM. Results NS-398 induced the cell apoptosis in K562 cells in a dose-dependent manner. After NS-398 treatment, the expression of Bcl-2 protein was downregulated, whereas the expression of Caspase-3 protein was upregulated. Moreover,the activity of Caspase-3 was increased in a dose-dependent way after NS-398 treatment. Conclusion Selective cyclooxygenase-2 inhibitor,NS-398,significantly induced apoptosis in K562 cells. The underlying mechanism might be related to the downregulation of Bcl-2 and the activation of Caspase-3.
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Objective To study the cell apoptosis after injecting NS398 in neonatal rat brain injured by hypoxia and ischemia.Methods The model of hypoxic-ischemic brain damage(HIBD)was established in 48 Wistar rats.Intraperitoneal injection of NS398 at dose of 5,20,40 mg/kg respectively was carried out in 36 HIBD rats 30 min before hypoxia.There were also sham operation group in which the normal saline took the place of NS398.Ischemic cortex and hippocampus were sampled for analysis at 24 h,and 7 d after the onset of hypoxic-ischemic damage.The expression and number of apoptotic cells in the cortex and hippocampus were examined with TUNEL.Results The percentage of TUNEL-positive cells in HIBD group was higher than that of sham operation group.The percentage of TUNEL-positive cells in NS398 groups significantly decreased as compared with that of HIBD group.NS398 group at dose of 20 mg/kg was of no difference with NS398 group at dose of 40 mg/kg,but significantly lower than NS398 group at dose 5 mg/kg.Conclusion NS398 can reduce the TUNEL-positive cells,and 20 mg/kg and 40 mg/kg are the more effective dosage.NS398 is of the effective capability to inhibit the brain damage in the growth period when HI happened.
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Objective Cyclooxygenase (COX), the key enzyme for synthesis of prostaglandins (PGs), exists in two isoforms (COX 1 and COX 2). Conventional non steroidal anti inflammatory drugs (NSAIDs) inhibit both COX 1 and COX 2 activities and induce serious gastrointestinal side effects. Specific COX 2 inhibitors are expected to cause fewer gastric side effects. The aim of this study was to investigate the effects of specific and non specific COX 2 inhibitors on gastric wound healing following acid induced injury. Methods Male Sprague Dawley rats were given 1 ml of 0.6 mol/L hydrochloric acid (HCl) into the stomach. Levels of COX 1 and COX 2 in gastric mucosa were analyzed using western blotting and immunohistochemical staining. At 10 minutes after the administration of the acid, the animals were given 0.4, 4 and 40 mg/kg of NS 398 (NS) or 40 mg/kg of indomethacin (IM). Control group was given 1% arabic gum (AG) in a volume of 5 ml/kg. The rats were sacrificed and laparotomized before and at 1, 3, 6, 12, 24, 48 h after acid administration. Lesion index (LI) was measured and morphological changes of gastric mucosa were assessed under light microscopy. Results Expression of COX 2 was enhanced mainly in surface epithelial cells and neck cells after HCl administration. NS and IM delayed the healing of gastric injury. At 12 h after acid administration, LI was (1.42 ? 0.23)% and (1.42 ? 0.29)% in the groups treated with 4 and 40 mg/kg of NS respectively, and (1.62 ? 0.44)% in the group treated with 40 mg/kg of IM, which was significantly higher than that in control group [(0.58?0.24)%, P
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Objective To study the expression of cyclooxygenase2 in hepatic inflammatory reaction of rats with sepsis and its effect on metabolism.Methods Fifty-four Wistar rats were randomly divided into 3 groups:Sham(A)group,sepsis model(B)group,and NS398 intervention(C)group.The rats were subjected to cecal ligation and puncture(CLP)for sepsis model or sham operation.RT-PCR was used to determine COX-2 mRNA expression,serum prealbumin(PA)and transferrin(TF)by radioimmunity.At the same time,ALT,AST,albumin determination and liver pathological changes were determined.Results(1)The expression of COX-2 mRNA was low in A group,higher in B and C groups,and higher in B than C group at each time period(P