糖尿病诱发大鼠神经退化及其对心肌缺血-再灌注神经反应性病理改变的影响

摘要

Objective The aim of the study was to investigate the diabetic neuro-degeneration and its changes in neuroreaction to myocardial ischemia and reperfusion,by evaluation of the altera-tion of noxious thermal threshold and expression of substance P (SP),calcitonin gene related peptide (CGRP)in dorsal root ganglia in upper thoracic segments (T1-5 )in diabetic rats.Methods Thirty two male Sprague-Dawley rats,weighing 180-200g,were randomly divided into control group (group C)and diabetic group (group DM),1 6 rats in each group.rats in DM group were fed with high sug-ar-fat diet for 14 weeks and were given streptozotocin (STZ,35 mg/mg,i.p.)at the end of the 4 th week,to set up diabetes experimental model.The animals in control group were fed with standard la-boratory diet.Tail flick latency to thermal stimulation was measured weekly.At the end of 10 weeks after administration of STZ,diabetic rats (and rats in control group)were further divided into myo-cardial ischemia-reperfusion group (group IR)and sham operation group (group Sham).The left an-terior descending branch of coronary artery was occluded for 30 min followed by reperfusion for 120 min,establishing myocardial ischemia-reperfusion.The histological immunofluorescence assay and Enzyme-linked immunosorbent assay (ELISA)were carried out to evaluate the changes of the expres-sions of CGRP and SP in the dorsal root ganglia.Results The tail flick latency was significantly in-creased in group DM,compared to the group C (P < 0.01).The immunoreactive materials for CGRP and SP in the sensory neurons in dorsal root ganglia of upper thoracic segments (T1-5 )were markedly declined in group DM (P <0.01 or P < 0.05).Furthermore,levels of SP and CGRP were signifi-cantly lower in the DRG of the group IR after myocardial ischemia-reperfusion,compared to that in the group sham (P <0.01).Conclusion Diabetes causes sensory denervation and obvious reduction of expression of SP and CGRP in the sensory neuron innervating heart during myocardial ischemia-reper-fusion,indicating impairment of adaptive reactivity of neuro-endocrine function of cardiac sensory nerves.%目的：通过观察分析糖尿病大鼠心脏感觉神经病变及其在心肌缺血-再灌注中上胸段背根神经节(DRG)内 P 物质(SP)、降钙素基因相关肽(CGRP)表达的变化,探讨糖尿病诱发感觉神经退化及其对心肌缺血-再灌注神经反应性病理改变的影响。方法雄性 SD 大鼠32只,180~200 g,其中16只以高糖高脂饲料喂养14周,并于喂养高糖高脂饲料4周后腹腔注射小剂量链脲佐菌素(STZ,35 mg/kg)制作糖尿病大鼠(DM 组)模型；另外16只采用一般饲料喂养作为对照组(C 组)。实验中每周测量一次甩尾潜伏期。DM 组注射 STZ 10周后随机分为糖尿病缺血-再灌注组(DM-IR组)、糖尿病假手术组(DM-Sham 组)两个亚组,采用结扎左冠状动脉前降支30 min 再灌注120 min的方法制备心脏缺血-再灌注模型。C 组随机分为缺血-再灌注组(C-IR 组)和假手术组(C-Sham 组)两个亚组。取 T1~5 DRG,采用免疫荧光技术和 ELISA 检测 SP 和 CGRP 的表达。结果与 C 组比较,第5~10周 DM 组大鼠甩尾潜伏期明显延长(P <0.01)。与 C-Sham 组比较,DM-Sham 组 DRG内 CGRP 和 SP 含量明显降低(P <0.01和 P <0.05)。与 C-IR 组比较,DM-IR 组 DRG 内 CGRP 和SP 含量均明显降低(P <0.01)。与 DM-Sham 组比较,DM-IR 组 DRG 内 CGRP 含量明显升高(P <0.01)。结论糖尿病诱发显著感觉神经功能退化；糖尿病大鼠在心肌缺血-再灌注中支配心脏的感觉神经细胞内 CGRP 和 SP 显著低于非糖尿病大鼠,提示神经细胞的反应性减退。