目的:观察酸柏栀油软胶囊(compound oil of jujube,arboruitae,and gardenia,COJAG)对记忆获得障碍模型小鼠的促智作用,分析COJAG促智作用GPR40的具体机制。方法:选购昆明种雄性小鼠152只,适应性喂养1周后,随机选择24只为空白对照组,其...目的:观察酸柏栀油软胶囊(compound oil of jujube,arboruitae,and gardenia,COJAG)对记忆获得障碍模型小鼠的促智作用,分析COJAG促智作用GPR40的具体机制。方法:选购昆明种雄性小鼠152只,适应性喂养1周后,随机选择24只为空白对照组,其他128只均用于记忆获得障碍模型的建立,128只小鼠建模成功120只,均衡随机分为5组,每组24只,即模型组,脑复康组,COJAG低、中、高剂量组。各组均按设定剂量灌胃给药,每日1次,均连续灌胃40天。结束后经Morris水迷宫实验检测小鼠行为学,免疫荧光组化检测GPR40在中枢神经系统中的表达和分布。结果:第1~5天,模型组小鼠寻找平台潜伏期及寻找平台路径高于其他组(P<0.05);用药后,COJAG组、脑复康组寻找平台潜伏期及寻找平台路径均较模型组降低(P<0.05);COJAG高剂量组寻找平台潜伏期及寻找平台路径最短,与低剂量组比较差异有统计学意义(P<0.05),但与中剂量组比较差异无统计学意义(P>0.05);较空白对照组,模型组小鼠第Ⅲ象限停留时间延长、第Ⅲ象限路程百分比降低、穿台次数减少(P<0.05);用药后,COJAG组、脑复康组小鼠第Ⅲ象限停留时间缩短、第Ⅲ象限路程百分比升高、穿台次数增加(P<0.05);COJAG高剂量组第Ⅲ象限停留时间最短、第Ⅲ象限路程百分比最高、穿台次数最多,与低剂量组比较差异有统计学意义(P<0.05),但与中剂量组比较差异无统计学意义(P>0.05)。较其他组,对照组小鼠GRP40表达最高,后由高至低依次为脑复康组、COJAG高剂量组、COJAG中剂量组、COJAG低剂量组,模型组表达最低。结论:使用酸柏栀油软胶囊可使脑组织GPR40升高,可以促进神经前体细胞增殖与神经元细胞突触增长,这可能是酸柏栀油软胶囊促记忆障碍小鼠学习能力提高的主要机制。展开更多
Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free...Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free fatty acid that has a high affinity to the rat GPR40, and examined its effect on cytosolic free calcium concentration ([Ca2+]i) in primary rat β-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic β-cells, and insulin secretion was assessed by enzyme-linked immunosorbent assay. Results LA acutely stimulated insulin secretion from primary cultured rat pancreatic islets. LA induced significant increase of [Ca2+]i in the presence of 5.6 mmol/L and 11.1 mmol/L glucose, which was reflected by increased Fluo-3 intensity under confocal microscopy recording. LA-stimulated increase in [Ca2+]i and insulin secretion were blocked by inhibition of GPR40/FFA1 expression in β-cells after GPR40/FFA1-specific antisense treatment. In addition, the inhibition of phospholipase C (PLC) activity by U73122, PLC inhibitor, also markedly inhibited the LA-induced [Ca2+]i increase. Conclusion LA activates GPR40/FFA1 and PLC to stimulate Ca2+ release, resulting in an increase in [Ca2+]i and insulin secretion in rat islet β-cells.展开更多
文摘目的:观察酸柏栀油软胶囊(compound oil of jujube,arboruitae,and gardenia,COJAG)对记忆获得障碍模型小鼠的促智作用,分析COJAG促智作用GPR40的具体机制。方法:选购昆明种雄性小鼠152只,适应性喂养1周后,随机选择24只为空白对照组,其他128只均用于记忆获得障碍模型的建立,128只小鼠建模成功120只,均衡随机分为5组,每组24只,即模型组,脑复康组,COJAG低、中、高剂量组。各组均按设定剂量灌胃给药,每日1次,均连续灌胃40天。结束后经Morris水迷宫实验检测小鼠行为学,免疫荧光组化检测GPR40在中枢神经系统中的表达和分布。结果:第1~5天,模型组小鼠寻找平台潜伏期及寻找平台路径高于其他组(P<0.05);用药后,COJAG组、脑复康组寻找平台潜伏期及寻找平台路径均较模型组降低(P<0.05);COJAG高剂量组寻找平台潜伏期及寻找平台路径最短,与低剂量组比较差异有统计学意义(P<0.05),但与中剂量组比较差异无统计学意义(P>0.05);较空白对照组,模型组小鼠第Ⅲ象限停留时间延长、第Ⅲ象限路程百分比降低、穿台次数减少(P<0.05);用药后,COJAG组、脑复康组小鼠第Ⅲ象限停留时间缩短、第Ⅲ象限路程百分比升高、穿台次数增加(P<0.05);COJAG高剂量组第Ⅲ象限停留时间最短、第Ⅲ象限路程百分比最高、穿台次数最多,与低剂量组比较差异有统计学意义(P<0.05),但与中剂量组比较差异无统计学意义(P>0.05)。较其他组,对照组小鼠GRP40表达最高,后由高至低依次为脑复康组、COJAG高剂量组、COJAG中剂量组、COJAG低剂量组,模型组表达最低。结论:使用酸柏栀油软胶囊可使脑组织GPR40升高,可以促进神经前体细胞增殖与神经元细胞突触增长,这可能是酸柏栀油软胶囊促记忆障碍小鼠学习能力提高的主要机制。
基金Supported by Grant from Department of Education of Liaoning Province (2008810)
文摘Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free fatty acid that has a high affinity to the rat GPR40, and examined its effect on cytosolic free calcium concentration ([Ca2+]i) in primary rat β-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic β-cells, and insulin secretion was assessed by enzyme-linked immunosorbent assay. Results LA acutely stimulated insulin secretion from primary cultured rat pancreatic islets. LA induced significant increase of [Ca2+]i in the presence of 5.6 mmol/L and 11.1 mmol/L glucose, which was reflected by increased Fluo-3 intensity under confocal microscopy recording. LA-stimulated increase in [Ca2+]i and insulin secretion were blocked by inhibition of GPR40/FFA1 expression in β-cells after GPR40/FFA1-specific antisense treatment. In addition, the inhibition of phospholipase C (PLC) activity by U73122, PLC inhibitor, also markedly inhibited the LA-induced [Ca2+]i increase. Conclusion LA activates GPR40/FFA1 and PLC to stimulate Ca2+ release, resulting in an increase in [Ca2+]i and insulin secretion in rat islet β-cells.
