糖尿病大鼠肠系膜动脉降钙素基因相关肽释放减少以及一氧化氮的作用

DECREASE OF CALCITONIN GENE-RELATED PEPTIDE RELEASE FROM MESENTERIC ARTERIAL BED IN DIABETIC RATS AND EFFECT OF NITRIC OXIDE

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 triggers the release of calcitonin generelated peptide (CGRP) from the mesenteric arterial bed, which is partially mediated by nitric oxide. In the present study, the changes of endotoxin-induced CGRP release from the isolated mesenteric arterial bed and the CGRP mRNA levels in dorsal root ganglia (DRG) of diabetic rats were studied in relation to the effect of nitric oxide. CGRP level in periusate and the steatly-state level of mRNA for CGar in DRG were determined by RIA and semi-quantitatively by RT-PCR. The results showed that endotoxin (1~25μg/ml) accumulated in perfusate caused concentration-dependent release of CGRP, which was significantly decreased in mesenteric arterial bed of diabetic rats. As compared with age-related control, the endotoxin (10 and 25μg/ml) -induced CGRP release in diabetic rats was attenuated by 27% and 40%, respectively. L-NAME, an inhibitor of nitric oxide synthase, inhibited the effect of endotoxin in dose of 10 and 25 μg/ml by 23% and 46%, respectively against the control rats. However, there was no inhihitory effect of LNAME on endotoxin-induced CGRP release in diabetic rats. The CGRP mRNA level in DRG showed no significant difference between the two groups. These results indicate that the response of the isolated mesenteric arterial bed to endotoxin-induced CGRP release in diabetic rats is significantly lower than that in control. The mechanism, at least in part,is due to a decrease of nitric oxide mediated release of CGRP, rather than a decrease of CGRP gene expression.