论文部分内容阅读
我们以前的工作已表明，内毒素可引起降钙素基因相关肽（CGRP）从大鼠肠系膜动脉床释放，此作用部分是通过一氧化氮介导的。我们在离体肠系膜动脉床研究了内毒素引起糖尿病大鼠CGRP释放的改变以及一氧化氮所起的作用。采用CGBP放射免疫分析法测定灌流液中CGRP含量，RT-PCR法测定背根神经节CGRPmRNA水平。结果显示：内毒素（1～25μg／ml）累积港流引起CGRP浓度依赖性地释放增多，此作用在糖尿病大鼠肠系膜动脉床明显减弱，内毒素10和25μg／ml引起的CGRP释放比对照组分别降低了27％和40％。研究其机制发现，一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）能使对照组大鼠肠系膜动脉床在10和25μg／ml内毒素刺激下CGRP的释放作用分别降低23％和46％，而在糖尿病大鼠L-NAME对内毒素的上述作用无明显影响；糖尿病大鼠和相应年龄的对照大鼠胸腰段脊髓背根神经节CGRPmRNA水平无明显差别。上述结果提示：糖尿病大鼠肠系膜动脉床对内毒素引起的CGRP释放反应明显降低，其原因部分是由于NO介导的CGRP释放作用消失，而不是CGRP基因表达减少。
Our previous work has shown that endotoxin causes the release of calcitonin gene-related peptide (CGRP) from the rat mesenteric artery bed, which is mediated in part by nitric oxide. We investigated the effects of endotoxin on the release of CGRP and the role of nitric oxide in diabetic rat mesenteric arterial beds. The content of CGRP in the perfusate was determined by CGBP radioimmunoassay. The level of CGRP mRNA in dorsal root ganglion was determined by RT-PCR. The results showed that the cumulative flow of endotoxin (1 ~ 25μg / ml) caused a concentration-dependent release of CGRP, which was significantly attenuated in the mesenteric artery bed of diabetic rats. The release of CGRP induced by endotoxin 10 and 25μg / ml was higher than that of the control group Decreased by 27% and 40% respectively. To investigate the mechanism, N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, was administered to rats in the mesenteric artery bed at 10 and 25 μg / The release of CGRP decreased by 23% and 46% respectively, while L-NAME had no effect on endotoxin in diabetic rats. In diabetic rats and corresponding age rats, CGRP mRNA No significant difference in level. These results suggest that the release of endotoxin-induced CGRP in the mesenteric artery bed of diabetic rats is significantly reduced due in part to NO-mediated disappearance of CGRP release rather than reduction of CGRP gene expression.