高位胸段硬膜外阻滞对心房颤动自主神经重构的影响

摘要

目的：观察高位胸段硬膜外阻滞（HTEB）对长期右心耳快速起搏诱发心房颤动（房颤）犬心房自主神经重构的影响，并探讨心房肌神经生长因子（NGF）在心房自主神经重构中的作用。　　方法：18只犬随机分为假手术组、对照组和HTEB组。对照组和HTEB组犬给予持续快速心房起搏建立房颤模型， HTEB组给予硬膜外腔注射0.5%利多卡因行高位胸段硬膜外阻滞。通过Masson染色检测犬心房肌胶原容积分数(CVF)改变，免疫组化法测定犬心房肌神经生长相关蛋白43（GAP43）及酪氨酸羟化酶（TH）表达，蛋白免疫印迹法检测犬心房肌NGF、GAP43及TH蛋白表达情况。　　结果：与对照组相比，右心耳快速起搏6周后，HTEB组犬心房肌CVF值显著降低； GAP43及TH神经萌出量显著减少（P<0.05）； NGF、GAP43及TH蛋白表达量显著减少（P<0.05~0.01）。与假手术组比较，HTEB组犬心房肌CVF值显著增加；GAP43及TH神经萌出量显著增加（P<0.05~0.01）； NGF、GAP43及TH蛋白表达量显著增加（P<0.05）。　　结论：长期右心耳快速起搏诱发犬房颤致心房肌神经不均一萌出，诱发自主神经重构，而NGF在其中发挥重要作用。HTEB可有效阻止房颤犬心房肌NGF表达上调，减轻自主神经重构。%Objective: To observe the impact of high thoracic epidural blockade (HTEB) on atrial autonomic nerve remodeling in dogs with atrial ifbrillation (AF) induced by long-term rapid right atrial appendage pacing and to explore the effect of nerve growth factor (NGF) on atrial autonomic nerve remodeling. Methods: AF model was established by consistent rapid atrial pacing for 6 weeks. 18 experimental dogs were randomly divided into 3 groups: Sham group, the dogs had no pacing while received normal saline injection; Control group, the dogs had pacing and normal saline injection; HTEB group, the dogs had pacing and 0.5% lidocaine injection for HTEB.n=6 in each group. Atrial myocardium collagen volume fraction (CVF) was examined by Masson staining; sprouting of NGF related protein 43 (GAP43) and tyrosine hydroxylase (TH) were assessed by immunohistochemistry; protein expressions of NGF, GAP43 and TH were measured by Western blot analysis. Results: Compared with Sham group, HTEB group showed decreased CVF and sprouting of GAP43, TH,P<0.05;reduced protein expressions of NGF, GAP43 and TH,P<0.05-0.01. Compared with Sham group, HTEB group presented increased CVF and sprouting of GAP43, TH,P<0.05-0.01; elevated protein expressions of NGF, GAP43 and TH,P<0.05. Conclusion: Long-term rapid atrial pacing induced AF dog had inhomogeneous sprouting of atrial myocardial nerve which may cause autonomic nerve remodeling; NGF played the important role in such process. HTEB could effectively inhibit NGF up-regulation and suppress the autonomic nerve remodeling in experimental dogs.