电针干预交感神经重构对心肌梗死后室性心律失常的预防作用及机制研究

It is known that ventricular arrythmias is a major cause of sudden cardiac deaths. Sympathetic neural remodeling is the main mechanism of the occurrence of ventricular arrhythmias which is the frequent complication of MI. Series of clinical research and animal studies have both indicated that acupuncture can treat arrhythmia by regulating the ANS( autonomic nervous system ) activity, but the sepecific nuroendocrine and molecular mechanism of how acupuncture affects the ANS activity is still unclear.Our previous study has indicated that Sympathetic neural remodeling can lead to arrhythmias.Based on what has been mentioned above,we hypothesised that electro-acupuncture stimulating at bilateral Neiguan (PC6) point could modify cardiac autonomic neural remodeling and thus exert an antiarrhythmic effect, and progressively reduce the occurrence of ventricular arrythmia after MI. We studied rats with MI after ligating the proximal left coronary artery,the rats were randomly allocated to receive electro-acupuncture (EA group), sham electro-acupuncture (EA-sham group), or neither electro-acupuncture nor antiarrhythmic therapy (CONTROL group) and metoprolol treatment(MET group). By Comparing the inducibility and duration of ventricular arrhythmias and also the nuroendocrine hormones and the change of the nerve growth factor morphology and the transformation of NGF mRNA expression in different groups after left cervicothoracic stellate ganglion stimulation,we would formulate the specific nuroendocrine and molecular mechanism of how acupuncture affects the sympathetic nerve activity, thus we would lay the theoretical foundation for clarifying the treatment of ventricular arrhythmias.

室性心律失常是心肌梗死后心脏性猝死的主要原因。交感神经重构是心肌梗死后室性心律失常发生的主要机制。临床研究和动物实验均证实针刺可通过调节自主神经活性预防和治疗心律失常，但针刺对自主神经活性影响的机制仍不清楚。前期研究发现交感神经重构可导致心律失常。据此，我们通过电针"内关"穴，调整心脏交感神经活性，进而逆转交感神经重构，使心脏交感神经分布和心肌细胞电活动均一性增加，减少梗死后室性心律失常发生。拟以心肌梗死后室性心律失常犬模型为研究对象，进行电针、假电针、药物及空白对照等干预，比较不同方法干预前后，犬心功能改善情况，室性心律失常发生率、室性心律失常评分，神经内分泌激素变化，梗死区、非梗死区心肌细胞离子通道电流、蛋白和mRNA表达变化，神经生长因子形态学、蛋白和mRNA表达变化；系统阐述电针干预调整心脏交感神经活性，逆转交感神经重构的机制，为阐明电针治疗心律失常奠定理论基础。

室性心律失常是心肌梗死后心脏性猝死的主要原因。心脏交感神经重构，特别是心肌梗死后心脏交感神经重构，导致局部心肌组织之间交感神经密度分布呈不均一性改变，形成了心肌梗死后室性心律失常发生的基质。本研究通过心肌梗死后室性心律失常犬模型为研究对象，进行电针、假电针的干预，发现(1)两组犬心梗后24小时内心梗后VA发生次数均较基础值显著增高，电针组刺激4周后VA发作次数较对照组显著降低(P<0.05)，两组犬心内膜3、心外膜1和心外膜2部位梗死后30min的VERP较基础值均显著缩短(P<0.05)，电针组刺激4周后逆转了上述3个部位的VERP缩短的改变(P<0.05)。两组犬梗死后30min的不应期离散度(dERP)均较基础值显著增大，电针刺激4周后dERP显著减小(与对照组比较，P<0.05)，电针组刺激4周后室颤阈值(VFT)与对照组比较显著增加(P<0.05)。(2)电针组左心室[(4510±657)μm/mm² vs (9674±1330)μm/mm²]、交感神经干[(3137±537)μm/mm² vs (13654±1160 ) μm/mm²]、正中神经[(8745±778)μm/mm² vs (14350±1554 ) μm/mm2]酪氨酸羟化酶(TH)阳性的神经纤维密度明显减少(P<0.05)，电针组胆碱乙酰转移酶(CHAT)阳性的神经纤维密度明显减少[(5871±598)μm/mm2 vs (10257±1030)μm/mm²，P<0.05)]，而电针组迷走神经[(7591±922)μm/mm² vs (654±120)μm/mm²]、正中神经[(8745±752)μm/mm² vs (5341±365)μm/mm²]。CHAT阳性的神经纤维密度显著增加(P<0.05)，电针组左心室梗死周边区和非梗死区ADRB1、TrkA 、P75NGFR的蛋白表达均显著低于对照组(P<0.05)。结论：针刺“内关”穴可抑制心肌梗死后自发性室性心律失常、降低室颤阈值，逆转并改善心梗引起的VERP缩短、dERP增大改变。针刺“内关”穴可改善梗死后的心脏自主神经重构，逆转心梗后交感神经活性增强的状态，并抑制心梗后梗死周边区的交感神经再生，改善肾上腺能受体分布异常。