AIM： To explore the effect of Astraga/us mongholicus polysaccharide （APS） on gene expression and mitogenactivated protein kinase （MAPK） transcriptional activity in intestinal epithelial cells （IEC）. METHODS： I...AIM： To explore the effect of Astraga/us mongholicus polysaccharide （APS） on gene expression and mitogenactivated protein kinase （MAPK） transcriptional activity in intestinal epithelial cells （IEC）. METHODS： IEC were divided into control group, lipopolysaccharide （LPS） group, LPS＋ 50 μg/mL APS group, LPS＋ 100 μg/mL APS group, LPS＋ 200 μg/mL APS group, and LPS＋ 500 μg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor （TNF）-α and interleukin （IL）-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS： The levels of TNF-α and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-α and IL-8 genes. APS did not block the activation of extracellular signal- regulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-α and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway.CONCLUSION： APS-modulated bacterial productmediated p38 signaling represents an attractive strategy for prevention and treatment of intestinal inflammation.展开更多
目的：评价右美托咪啶对神经病理性痛大鼠脊髓背角神经元磷酸化胞外反应激酶（phosphoryltion of extracellular regulated proteinkinases，pERK）、磷酸化cAMP反应元件结合蛋白（phosphoryltion of Camp response element bound prot...目的：评价右美托咪啶对神经病理性痛大鼠脊髓背角神经元磷酸化胞外反应激酶（phosphoryltion of extracellular regulated proteinkinases，pERK）、磷酸化cAMP反应元件结合蛋白（phosphoryltion of Camp response element bound protein，pCREB）蛋白表达的影响。方法：健康成年雄性Wistar大鼠54只，6～8周龄，体重180-220g，采用随机数字表法，将其分为3组（Il=18）：假手术组（s组）、慢性神经病理性痛组（C组）和右美托咪啶组（D组）。S组仅分离坐骨神经但不结扎，C组和D组采用结扎坐骨神经的方法制备大鼠坐骨神经慢性压迫性损伤（chronicconstriction injury，CCI）的神经病理性痛模型，D组于术后即刻开始至处死前1d腹腔注射右美托咪啶50μg／kg，1次，d，s组和C组注射等容量生理盐水。于术前1d、术后3、7、14d时以缩足阈值（pawwithdrawal threshold，P、ⅣT）测定大鼠机械痛阈和辐射热的缩足潜伏期（pawwithdrawl latency，PWL）测定大鼠的热痛阈，并于术后测定痛阈后灌注处死大鼠，取L4．6脊髓组织，采用免疫组织化学法检测脊髓背角神经元pERK、pCREB的表达水平。结果：与s组比较，c组和D组术后3、7、14d时MWT降低，TWL缩短，脊髓背角pERK、pCREB表达上调（P〈0．05）；与c组比较，D组术后3、7、14d时MWT升高，T、TWL延长，脊髓背角pERK、pCREB表达下调（P〈0．05）。与术前1d比较，c组和D组术后3、7、14d时MWT降低，TWL缩短：与术后3d时比较。C组和D组7、14d时MWT降低，TwL缩短，脊髓背角pERK、pCREB表达上调（P〈0．05）。结论：右关托咪啶可减轻大鼠慢性神经病理性痛，抑制pERK、pCREB的表达可能是其作用机制之一。展开更多
Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate co...Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.展开更多
文摘AIM： To explore the effect of Astraga/us mongholicus polysaccharide （APS） on gene expression and mitogenactivated protein kinase （MAPK） transcriptional activity in intestinal epithelial cells （IEC）. METHODS： IEC were divided into control group, lipopolysaccharide （LPS） group, LPS＋ 50 μg/mL APS group, LPS＋ 100 μg/mL APS group, LPS＋ 200 μg/mL APS group, and LPS＋ 500 μg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor （TNF）-α and interleukin （IL）-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS： The levels of TNF-α and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-α and IL-8 genes. APS did not block the activation of extracellular signal- regulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-α and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway.CONCLUSION： APS-modulated bacterial productmediated p38 signaling represents an attractive strategy for prevention and treatment of intestinal inflammation.
文摘目的：评价右美托咪啶对神经病理性痛大鼠脊髓背角神经元磷酸化胞外反应激酶（phosphoryltion of extracellular regulated proteinkinases，pERK）、磷酸化cAMP反应元件结合蛋白（phosphoryltion of Camp response element bound protein，pCREB）蛋白表达的影响。方法：健康成年雄性Wistar大鼠54只，6～8周龄，体重180-220g，采用随机数字表法，将其分为3组（Il=18）：假手术组（s组）、慢性神经病理性痛组（C组）和右美托咪啶组（D组）。S组仅分离坐骨神经但不结扎，C组和D组采用结扎坐骨神经的方法制备大鼠坐骨神经慢性压迫性损伤（chronicconstriction injury，CCI）的神经病理性痛模型，D组于术后即刻开始至处死前1d腹腔注射右美托咪啶50μg／kg，1次，d，s组和C组注射等容量生理盐水。于术前1d、术后3、7、14d时以缩足阈值（pawwithdrawal threshold，P、ⅣT）测定大鼠机械痛阈和辐射热的缩足潜伏期（pawwithdrawl latency，PWL）测定大鼠的热痛阈，并于术后测定痛阈后灌注处死大鼠，取L4．6脊髓组织，采用免疫组织化学法检测脊髓背角神经元pERK、pCREB的表达水平。结果：与s组比较，c组和D组术后3、7、14d时MWT降低，TWL缩短，脊髓背角pERK、pCREB表达上调（P〈0．05）；与c组比较，D组术后3、7、14d时MWT升高，T、TWL延长，脊髓背角pERK、pCREB表达下调（P〈0．05）。与术前1d比较，c组和D组术后3、7、14d时MWT降低，TWL缩短：与术后3d时比较。C组和D组7、14d时MWT降低，TwL缩短，脊髓背角pERK、pCREB表达上调（P〈0．05）。结论：右关托咪啶可减轻大鼠慢性神经病理性痛，抑制pERK、pCREB的表达可能是其作用机制之一。
基金supported by National Natural Science Fundation of China (No.30870835,30821002,and 30900444)National Basic Research Program of China (No. 2007CB512303,2007CB512502,and 2006CB500807)Postdoctoral Fundation of China (No.20080440578)
文摘Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.
