Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats
Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats
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DOI：
10.1053/gast.1997.v113.pm9352855
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发表时间：
1997-11-01
期刊：
影响因子：
29.4
通讯作者：
Owyang, C
中科院分区：
文献类型：
--
作者：
Takahashi, T;Nakamura, K;Owyang, C
背景和目标：糖尿病患者胃调节缺陷的机制尚不清楚，本研究的目的是研究这种异常是否是由于胃肌间神经丛中一氧化氮合酶（NOS）表达受损继发的一氧化氮通路缺陷所致。为了验证这一假设，我们研究了非肾上腺素能，非胆碱能（NANC）舒张，NOS活性，NADPH黄递酶组织化学，NOS免疫组织化学，结果：正常对照组大鼠胃神经肌肉对透壁刺激表现出频率依赖性NANC舒张反应。糖尿病BB/W大鼠胃肌间神经丛NOS免疫反应阳性细胞数和NOS活性均明显减少，提示糖尿病时NOS合成受损，北方印迹分析显示糖尿病BB/W大鼠胃组织NOS mRNA条带密度在9.5 bp处明显降低。结论：糖尿病胃舒张功能障碍主要是胃肌间神经丛NOS表达受损所致。
Background & Aims: The mechanism responsible for defective gastric accommodation in diabetes is unknown, The aim of this study was to investigate if this abnormality is due to a defective nitric oxide pathway secondary to impaired nitric oxide synthase (NOS) expression in the gastric myenteric plexus, Methods: To test this hypothesis, we studied nonadrenergic, noncholinergic (NANC) relaxation, NOS activity, NADPH diaphorase histochemistry, NOS immunohistochemistry, NOS immunoblotting, and NOS messenger RNA expression in the gastric myenteric plexus of spontaneously diabetic biobreeding/Worcester (BB/W) rats, Age-matched nondiabetic Wistar rats were used as controls, Results: Gastric neuromuscular preparations from control rats showed a frequency-dependent NANC relaxation in response to transmural stimulation. This relaxation was markedly antagonized by NG-nitro-L-arginine-methyl ester, indicating mediation by the neuronal release of NO, The NANC relaxation in gastric muscle preparations obtained from diabetic BB/W rats was significantly impaired, The number of NOS-immunoreactive cells in the gastric myenteric plexus and the NOS activity were significantly reduced in diabetic BB/W rats, suggesting that NOS synthesis is impaired in diabetes, Northern blot analysis showed that the density of NOS messenger RNA bands at 9.5 kilobases was significantly reduced in the gastric tissues of diabetic BB/W rats, Conclusions: These results indicate that gastric relaxation in diabetics is hampered mainly by impaired NOS expression in the gastric myenteric plexus.