目的:了解糖尿病大鼠胃肠动力障碍时,回肠肌间神经丛有无形态学异常,以及第Ⅰ组代谢型谷氨酸受体mGluR1、mGluR5的表达变化,探讨谷氨酸能神经在糖尿病胃肠病变发生中的作用.方法:40只大鼠随机分为糖尿病组和对照组,给与高脂饮食结合腹...目的:了解糖尿病大鼠胃肠动力障碍时,回肠肌间神经丛有无形态学异常,以及第Ⅰ组代谢型谷氨酸受体mGluR1、mGluR5的表达变化,探讨谷氨酸能神经在糖尿病胃肠病变发生中的作用.方法:40只大鼠随机分为糖尿病组和对照组,给与高脂饮食结合腹腔注射STZ 30 mg/kg造糖尿病模型.运用肌间神经丛铺片观察谷氨酸能神经的分布及形态特征,并对其神经节和神经元进行定量研究,以及运用免疫荧光染色和RT-PCR方法观察大鼠回肠肠神经系统肌间神经丛的代谢型谷氨酸受体mGluR1、mGluR5的表达变化.结果:糖尿病大鼠肠神经系统肌间神经丛的谷氨酸能神经节和神经元的数目较对照组明显减少(mGluR1:4.5±3.1 vs 7.3±2.4;142.25±28.24vs 175.34±34.83,均P<0.05;mGluR5:4.3±2.1 vs 7.9±2.8,133.37±35.73 vs 168.34±32.66,均P<0.05),荧光强度较对照组减弱(mGluR1:145.23±28.78 vs 167.72±30.56,均P<0.05;mGluR5:141.54±18.46 vs 172.53±29.74,均P<0.05),mGluR1、mGluR5受体mRNA表达减少(1.05±0.27 vs 1.43±0.47,0.95±0.30vs 1.60±0.39,均P<0.01).结论:糖尿病大鼠回肠肠壁的肌间神经丛的神经节和神经元数目减少,以及兴奋性递质受体mGluR1、mGluR5的表达减少是导致胃肠道肌层兴奋性降低,肌层收缩减弱,引起糖尿病胃肠病变的一个重要机制.展开更多
Many studies have reported long-term modulation of metabotropic glutamate receptor 5 (mGluR5) by inflammatory processes and a pharmacological modulation of mGluR5 is known to regulate anxiety level. However, it is not...Many studies have reported long-term modulation of metabotropic glutamate receptor 5 (mGluR5) by inflammatory processes and a pharmacological modulation of mGluR5 is known to regulate anxiety level. However, it is not known if non-pharmacological modulation of mGluR5 by inflammation impaired the unconditional level of anxiety. In this study, we investigated this relation in LPS prenatal immune challenge (120 μg/kg, 3x i.p. injection in late gestation), a developmental model of neuroinflammation in which some studies have reported hypo-anxious phenotype. Using positron emission tomographic imaging (PET) approaches, we have demonstrated a decrease in the binding potential of [18F]fluoro-5-(2-pyridinylethynyl)benzonitrile([18F]FPEB, a radioligand for mGluR5) in hippocampus of adolescent offspring prenatally exposed to LPS, without significant change in the binding of [11C]peripheral benzodiazepine receptor 28 ([11C]PBR28), an inflammatory marker. In addition, dark-light box emergence test revealed a lower level of anxiety in LPS-exposed offspring and this behavioural phenotype was associated with the binding potential of [18F]FPEB in hippocampus. These results confirm that neuroinflammation during developmental phase modulates the physiology of mGluR5 and this alteration can be associated with behavioural phenotype related to anxiety. In addition, this study supports a hypotheses that mGluR5 could be used as a diagnostic target in anxiety.展开更多
Objective： To study the morphologic abnormalities of the myenteric plexus in diabetic rats and to explore the mechanism of their effect on gastrointestinal motility. Methods： Forty rats were randomly divided into a ...Objective： To study the morphologic abnormalities of the myenteric plexus in diabetic rats and to explore the mechanism of their effect on gastrointestinal motility. Methods： Forty rats were randomly divided into a diabetic group and a control group, Gastric emptying and small intestine transit rates were measured and histologic and molecular changes in glutamatergic nerves in the ileal myenteric plexus were observed, mGluR5 receptor and EAAC1 transporter changes in the diabetic rats were studied using fluorescence immunohistochemistry and RT-PCR. Results：Eighteen weeks after the establishment of the diabetic rats model, gastric emptying and small intestine transit rates were found to be significantly delayed in the diabetic group when compared with the control group. The density of glutamatergic ganglia and neurons in the ileal myenterie plexus were significantly decreased in the diabetic group when compared with control group（P 〈 0.05） and the mGluR5 receptors and EAAC1 transporters were downregulated in the diabetic rats（P 〈 0.05）. Conclusion： Decreased glutamatergic enteric ganglia and neurons and decreased mGluR5 receptors and EAAC1 transporters in the intestinal myenteric plexus is one of the mechanisms of diabetic gastroenteropathy in rats.展开更多
文摘目的:了解糖尿病大鼠胃肠动力障碍时,回肠肌间神经丛有无形态学异常,以及第Ⅰ组代谢型谷氨酸受体mGluR1、mGluR5的表达变化,探讨谷氨酸能神经在糖尿病胃肠病变发生中的作用.方法:40只大鼠随机分为糖尿病组和对照组,给与高脂饮食结合腹腔注射STZ 30 mg/kg造糖尿病模型.运用肌间神经丛铺片观察谷氨酸能神经的分布及形态特征,并对其神经节和神经元进行定量研究,以及运用免疫荧光染色和RT-PCR方法观察大鼠回肠肠神经系统肌间神经丛的代谢型谷氨酸受体mGluR1、mGluR5的表达变化.结果:糖尿病大鼠肠神经系统肌间神经丛的谷氨酸能神经节和神经元的数目较对照组明显减少(mGluR1:4.5±3.1 vs 7.3±2.4;142.25±28.24vs 175.34±34.83,均P<0.05;mGluR5:4.3±2.1 vs 7.9±2.8,133.37±35.73 vs 168.34±32.66,均P<0.05),荧光强度较对照组减弱(mGluR1:145.23±28.78 vs 167.72±30.56,均P<0.05;mGluR5:141.54±18.46 vs 172.53±29.74,均P<0.05),mGluR1、mGluR5受体mRNA表达减少(1.05±0.27 vs 1.43±0.47,0.95±0.30vs 1.60±0.39,均P<0.01).结论:糖尿病大鼠回肠肠壁的肌间神经丛的神经节和神经元数目减少,以及兴奋性递质受体mGluR1、mGluR5的表达减少是导致胃肠道肌层兴奋性降低,肌层收缩减弱,引起糖尿病胃肠病变的一个重要机制.
文摘Many studies have reported long-term modulation of metabotropic glutamate receptor 5 (mGluR5) by inflammatory processes and a pharmacological modulation of mGluR5 is known to regulate anxiety level. However, it is not known if non-pharmacological modulation of mGluR5 by inflammation impaired the unconditional level of anxiety. In this study, we investigated this relation in LPS prenatal immune challenge (120 μg/kg, 3x i.p. injection in late gestation), a developmental model of neuroinflammation in which some studies have reported hypo-anxious phenotype. Using positron emission tomographic imaging (PET) approaches, we have demonstrated a decrease in the binding potential of [18F]fluoro-5-(2-pyridinylethynyl)benzonitrile([18F]FPEB, a radioligand for mGluR5) in hippocampus of adolescent offspring prenatally exposed to LPS, without significant change in the binding of [11C]peripheral benzodiazepine receptor 28 ([11C]PBR28), an inflammatory marker. In addition, dark-light box emergence test revealed a lower level of anxiety in LPS-exposed offspring and this behavioural phenotype was associated with the binding potential of [18F]FPEB in hippocampus. These results confirm that neuroinflammation during developmental phase modulates the physiology of mGluR5 and this alteration can be associated with behavioural phenotype related to anxiety. In addition, this study supports a hypotheses that mGluR5 could be used as a diagnostic target in anxiety.
文摘Objective： To study the morphologic abnormalities of the myenteric plexus in diabetic rats and to explore the mechanism of their effect on gastrointestinal motility. Methods： Forty rats were randomly divided into a diabetic group and a control group, Gastric emptying and small intestine transit rates were measured and histologic and molecular changes in glutamatergic nerves in the ileal myenteric plexus were observed, mGluR5 receptor and EAAC1 transporter changes in the diabetic rats were studied using fluorescence immunohistochemistry and RT-PCR. Results：Eighteen weeks after the establishment of the diabetic rats model, gastric emptying and small intestine transit rates were found to be significantly delayed in the diabetic group when compared with the control group. The density of glutamatergic ganglia and neurons in the ileal myenterie plexus were significantly decreased in the diabetic group when compared with control group（P 〈 0.05） and the mGluR5 receptors and EAAC1 transporters were downregulated in the diabetic rats（P 〈 0.05）. Conclusion： Decreased glutamatergic enteric ganglia and neurons and decreased mGluR5 receptors and EAAC1 transporters in the intestinal myenteric plexus is one of the mechanisms of diabetic gastroenteropathy in rats.
