慢性肾缺血致心功能不全时大鼠心肌组织降钙素基因相关肽含量的变化

Changes and Mechanisms of Content of Calcitonin Gene-Related Peptide in Myocardium in Rat with Cardiac Insufficiency Caused by Chronic Renal Ischemia

目的观察慢性肾缺血导致心功能不全时心肌组织降钙素基因相关肽(CGRP)含量变化,并分析变化的机制。方法将40只Wistar大鼠分为,狭窄对照组(n=15)和狭窄治疗组(n=15),均采用两肾动脉之间腹主动脉缩窄术造成单侧慢性肾缺血。假手术组(n=10)仅分离腹主动脉。至术后16周狭窄治疗组给予阿魏酸钠40mg/kg腹腔内注射,狭窄对照组和假手术组均给予同等剂量生理盐水。治疗2周后,测定颈动脉压、左心功能,处死大鼠后测定心肌组织CGRP、ET-1和NO含量,分别测定心肌和脊髓背根神经节CGRP mRNA表达。结果狭窄对照组和狭窄治疗组心功能均下降,但狭窄治疗组心脏舒张功能优于狭窄对照组。狭窄对照组心肌内ET-1含量明显增加,CGRP含量明显下降。狭窄治疗组心肌内ET-1含量较对照组减少,CGRP含量略增高。各组心肌CGRP mRNA表达无明显差异。狭窄治疗组脊髓背根神经节CGRP mRNA表达较假手术组增加。结论大鼠慢性肾缺血导致心脏组织ET-1持续激活,CGRP、NO合成受损,与心功能下降密切相关。心功能不全时,脊髓背根神经节CGRP mRNA表达代偿性增高,但心脏血管内皮组织受损可能是心脏CGRP含量下降的主要因素。

Objective To investigate the changes of content of calcitonin gene-related peptide in myocardium and possible mechanisms in rat with cardiac insufficiency caused by chronic renal ischemia, Methods Male wistar rats were randomly divided into control group （group C, n= 15）, experimental group （group E, n= 15） and sham operation group （group S, n= 10）. Ligation by silk suture was performed on abdominal aorta between right and left renal arteries in both groups C and E, The aorta was not ligated in group S. At 16 weeks after operation, injection of sodium ferulic （40 mg/kg） was given intraperitonealy in group E and normal saline was given in other two groups. Blood pressure, heart function and content of ET-1, CGRP and NO in myocardium were measured two weeks after the therapy. Expression of CGRP mRNA was detected in myocardium and dorsal root ganglion. Results At the end of experiment, cardiac function of rat in groups C and E was significantly decreased as compared with the rats in group S, but diastolic function was improved in group E as compared with that in group C. The content of ET-1 in myocardium in group C was higher than that in group S whereas the content of CGRP was lower. The content of ET-1 in myocardium in group E was decreased than that in group C, accompanied with a slightly increased content of CGRP. There were no differences in expression of CGRP mRNA among the three groups. The expression of CGRP mRNA in dorsal root ganglion was higher in group Ethan in group C. Conclusion The activation of ET-1 in myocardium caused by chronic renal ischemia may impair the synthesis of CGRP and NO in myocardium and may result in cardiac insufficiency. As cardiac insufficiency occurs, expression of CGRP mRNA in DRG is increased compensationally. The decrease of content of CGRP in myocardium may attribute to the impairment of cardiac vascular endothelium which also synthesizes CGRP.