AIM： To determine whether a specific adenosine A2A receptor agonist （ATL-146e） can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory c...AIM： To determine whether a specific adenosine A2A receptor agonist （ATL-146e） can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines. METHODS： Gastric lesions were produced by oral gavage of aspirin （200 mg/kg） and HCI （0.15 mol/L, 8.0 mL/kg）. 4-{3-[6-Amino-9-（5-ethylcarbamoyl-3,4- dihydroxy-tetrahydro-furan-2-yl）-9H-purin-2-yl]-prop-2- ynyl}-cyclohexanecarboxylic acid methyl ester （ATL-146e, 2.5-5μg/kg, IP） was injected 30 min before the administration of aspirin. Tissue myeloperoxidase （MPO） concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 （PGE2） production and gastric secretion. RESULTS： Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions （ulcer index） in control rats was 29.8±7.75 mm and was reduced to 3.8±1.42 mm alter pretreatment with 5.0 g/kg ATL-146e （P〈 0.01）. The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e. Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e. CONCLUSION： The specific adenosine A2A receptor agonist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.展开更多
Objective To study the effect of the serum derived from the rats treated with electroacupunctre at Stomach Meridian acupoints on the EGFR signal transduction pathway in gastric mucosal cells. Methods Sixty rats were r...Objective To study the effect of the serum derived from the rats treated with electroacupunctre at Stomach Meridian acupoints on the EGFR signal transduction pathway in gastric mucosal cells. Methods Sixty rats were randomly divided into 5 groups： model group, Stomach （ST） Meridian group, Gallbladder （GB） Meridian group, ST＋ PD153035 group and GB＋ PD153035 group. Water-immersion and restrained stress method was adopted for preparation of the stress-induced gastric ulcer rat model, and the gastric mucosa cells were separated by using pronase digestion method. Gastric mucosa cells were incubated respectively with PD153035, EGFR inhibitor and the serum; PLCγ-1＇s expression level in gastric mucosa cells was tested by enzyme-linked immunosorbant assay （ELISA）, and PKC activity by isotope mingling method; and reverse transcription polymerase chain reaction assay （RT-PCR） was used for testing expression level of c-myc gene. Results The expression levels of PLCγ-1 ,PKC and c- myc gene were lower in gastric mucosa cells in the model group; there were relatively high expression levels of PLCγ-1 ,PKC and c-myc gene in the ST Meridian group and the GB Meridian group, with the highest expression levels of PLCγ-1 ,PKC and c-myc gene in the ST Meridian, and with a significant difference between the ST Meridian group and the GB Meridian group （P〈0.01 ） ; and relative lower expression levels of PLCγ-1, PKC and c-myc gene were seen in the ST ＋ PD153035 group and the GB ＋ PD153035 group; and there was a significant difference between the ST Meridian group and the ST ＋ PD153035 group （P〈0.01）. Conclusion There was a close correlation between the healing effect of electroacupuncture and activation of the EGFR signal transduction pathway in the impaired gastric mucosa cells, which was also one proof for the TCM theory： ＂There is relative specificity between the meridians and viscera＂.展开更多
Objective： To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor （EGFR）, phosphorylation extracellular signal-regulated kinase I/2 （p-ERKI/2） and activa...Objective： To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor （EGFR）, phosphorylation extracellular signal-regulated kinase I/2 （p-ERKI/2） and activated protein-1 （AP-2）, the key factors of extracellular signal-regulated kinase signaling transduction pathway in gastric tissue of rats with stress-induced gastric mucosal damage, and to discuss the mechanisms of moxibustion therapy in promoting the restoration of damaged gastric mucosa. Methods： Thirty Sprague-Dawley （SD） rats were randomly divided into a normal group, a model group, and a moxibustion group using the random digits table, 10 in each group. Except the rats in the normal group, rats in the other two groups were used to make stress-induced gastric mucosal damage model using restraint and cold stress. Before modeling, rats in the moxibustion group were alternately treated with moxibustion a/t Zusanli （ST 36） and Zhongwan （CV 12）, or Pishu （BL 20） and Weishu （BL 22）, once a day, for a total of 8 d. Histolo^cal changes of gastric mucosa were observed under the light microscopy, the expression of gastric tissue p-ERKI/2 was detected by immunohistochemistry assay, and the protein levels of EGFR and AP-I were measured by Western blots. Results： Compared with rats in the normal group, gastric mucosal damage was more serious, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the model group （P〈0.01, P〈O.05, P〈0.05）. Compared with rats in the model group, gastric mucosal damage was milder, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the moxibustion group （all P〈0.01）. Conclusion： Moxibustion at Zusanli （ST 36）, Zhongwan （CV 12）, Pishu （BL 20） and Weishu （BL 21） could increase EGFR, p-ERK1/2 and AP-1 expression levels in gastric tissue of stress-induced gastric mucosal damage rats, maintain the information transfer function of ERK signaling transduction pathway, and promote restoration of gastric mucosal damage.展开更多
文摘AIM： To determine whether a specific adenosine A2A receptor agonist （ATL-146e） can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines. METHODS： Gastric lesions were produced by oral gavage of aspirin （200 mg/kg） and HCI （0.15 mol/L, 8.0 mL/kg）. 4-{3-[6-Amino-9-（5-ethylcarbamoyl-3,4- dihydroxy-tetrahydro-furan-2-yl）-9H-purin-2-yl]-prop-2- ynyl}-cyclohexanecarboxylic acid methyl ester （ATL-146e, 2.5-5μg/kg, IP） was injected 30 min before the administration of aspirin. Tissue myeloperoxidase （MPO） concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 （PGE2） production and gastric secretion. RESULTS： Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions （ulcer index） in control rats was 29.8±7.75 mm and was reduced to 3.8±1.42 mm alter pretreatment with 5.0 g/kg ATL-146e （P〈 0.01）. The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e. Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e. CONCLUSION： The specific adenosine A2A receptor agonist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.
基金Supported by the Natural Science Foundation of Jiangxi Province (No :2008 GZY0022)the Technology Plan of Jiangxi Provincial Department of Education (No :GJJ09280)
文摘Objective To study the effect of the serum derived from the rats treated with electroacupunctre at Stomach Meridian acupoints on the EGFR signal transduction pathway in gastric mucosal cells. Methods Sixty rats were randomly divided into 5 groups： model group, Stomach （ST） Meridian group, Gallbladder （GB） Meridian group, ST＋ PD153035 group and GB＋ PD153035 group. Water-immersion and restrained stress method was adopted for preparation of the stress-induced gastric ulcer rat model, and the gastric mucosa cells were separated by using pronase digestion method. Gastric mucosa cells were incubated respectively with PD153035, EGFR inhibitor and the serum; PLCγ-1＇s expression level in gastric mucosa cells was tested by enzyme-linked immunosorbant assay （ELISA）, and PKC activity by isotope mingling method; and reverse transcription polymerase chain reaction assay （RT-PCR） was used for testing expression level of c-myc gene. Results The expression levels of PLCγ-1 ,PKC and c- myc gene were lower in gastric mucosa cells in the model group; there were relatively high expression levels of PLCγ-1 ,PKC and c-myc gene in the ST Meridian group and the GB Meridian group, with the highest expression levels of PLCγ-1 ,PKC and c-myc gene in the ST Meridian, and with a significant difference between the ST Meridian group and the GB Meridian group （P〈0.01 ） ; and relative lower expression levels of PLCγ-1, PKC and c-myc gene were seen in the ST ＋ PD153035 group and the GB ＋ PD153035 group; and there was a significant difference between the ST Meridian group and the ST ＋ PD153035 group （P〈0.01）. Conclusion There was a close correlation between the healing effect of electroacupuncture and activation of the EGFR signal transduction pathway in the impaired gastric mucosa cells, which was also one proof for the TCM theory： ＂There is relative specificity between the meridians and viscera＂.
基金supported by National Basic Research Program of China(973 Program,No.2015CB554502)National Natural Science Foundation of China(No.81202770,No.81574082)+5 种基金Special Research Fund for the Doctoral Program of Higher Education of China for New Teachers(No.20124323120002)Hunan Provincial Natural Science Foundation of China(No.13JJ6060)Foundation for the Author of Excellent Doctoral Dissertation of Hunan Province(No.YB2013B037)Fund Project of Hunan Province Education Office(No.14B129)2013 Project of Scientific and Technological Innovation and Entrepreneurship Platform for Huxiang Youth2013 Training Project of 225 for High-level Medical Personnel of Hunan Province~~
文摘Objective： To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor （EGFR）, phosphorylation extracellular signal-regulated kinase I/2 （p-ERKI/2） and activated protein-1 （AP-2）, the key factors of extracellular signal-regulated kinase signaling transduction pathway in gastric tissue of rats with stress-induced gastric mucosal damage, and to discuss the mechanisms of moxibustion therapy in promoting the restoration of damaged gastric mucosa. Methods： Thirty Sprague-Dawley （SD） rats were randomly divided into a normal group, a model group, and a moxibustion group using the random digits table, 10 in each group. Except the rats in the normal group, rats in the other two groups were used to make stress-induced gastric mucosal damage model using restraint and cold stress. Before modeling, rats in the moxibustion group were alternately treated with moxibustion a/t Zusanli （ST 36） and Zhongwan （CV 12）, or Pishu （BL 20） and Weishu （BL 22）, once a day, for a total of 8 d. Histolo^cal changes of gastric mucosa were observed under the light microscopy, the expression of gastric tissue p-ERKI/2 was detected by immunohistochemistry assay, and the protein levels of EGFR and AP-I were measured by Western blots. Results： Compared with rats in the normal group, gastric mucosal damage was more serious, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the model group （P〈0.01, P〈O.05, P〈0.05）. Compared with rats in the model group, gastric mucosal damage was milder, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the moxibustion group （all P〈0.01）. Conclusion： Moxibustion at Zusanli （ST 36）, Zhongwan （CV 12）, Pishu （BL 20） and Weishu （BL 21） could increase EGFR, p-ERK1/2 and AP-1 expression levels in gastric tissue of stress-induced gastric mucosal damage rats, maintain the information transfer function of ERK signaling transduction pathway, and promote restoration of gastric mucosal damage.
