日本一个研究小组经动物实验证实，一种阻碍神经再生的蛋白质出现异常可引发心律不齐，从而导致猝死。
由庆应义塾大学、札幌医科大学和名古屋大学等组成的研究小组在９日《自然·医学》网络版上发表论文说，蛋白质“ｓｅｍａｐｈｏｒｉｎ－３ａ”合成量不足或过量都会使心脏交感神经的分布形式发生异常，导致心脏电活动不稳定，从而引发致命的心律不齐。
心脏的搏动频率由交感神经调节。研究人员通过基因技术，使实验鼠体内不能生成上述蛋白质，之后检查实验鼠心脏，发现交感神经的分布无序。这种实验鼠有８０％出生不到１周就会死亡。研究人员对幸存下来的老鼠进行研究发现，它们的心律不齐，心跳有时会突然停止。
另外，研究人员还培养了一些可以过量分泌“ｓｅｍａｐｈｏｒｉｎ－３ａ”蛋白质的实验鼠，发现它们的心脏交感神经大量减少，出生８周以后，心跳异常、猝死的倾向比较明显。
Nature Medcine，Published online: 8 April 2007; | doi:10.1038/nm1570
Sema3a maintains normal heart rhythm through sympathetic innervation patterning
Masaki Ieda1, 2, Hideaki Kanazawa1, 2, Kensuke Kimura1, Fumiyuki Hattori1, Yasuyo Ieda1, Masahiko Taniguchi3, Jong-Kook Lee4, Keisuke Matsumura1, 2, Yuichi Tomita1, Shunichiro Miyoshi2, Kouji Shimoda5, Shinji Makino1, Motoaki Sano1, Itsuo Kodama4, Satoshi Ogawa2 & Keiichi Fukuda1
1 Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
2 Cardiology Division, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
3 Department of Biochemistry, Cancer Research Institute, Sapporo Medical University School of Medicine, S-1, W-17, Chuo-ku, Sapporo 060-8556, Japan.
4 Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
5 Laboratory Animal Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Correspondence should be addressed to Keiichi Fukuda kfukuda@sc.itc.keio.ac.jp
Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a, establishes cardiac sympathetic innervation patterning. Sema3a is abundantly expressed in the trabecular layer in early-stage embryos but is restricted to Purkinje fibers after birth, forming an epicardial-to-endocardial transmural sympathetic innervation patterning. Sema3a -/- mice lacked a cardiac sympathetic innervation gradient and exhibited stellate ganglia malformation, which led to marked sinus bradycardia due to sympathetic dysfunction. Cardiac-specific overexpression of Sema3a in transgenic mice (SemaTG) was associated with reduced sympathetic innervation and attenuation of the epicardial-to-endocardial innervation gradient. SemaTG mice demonstrated sudden death and susceptibility to ventricular tachycardia, due to catecholamine supersensitivity and prolongation of the action potential duration. We conclude that appropriate cardiac Sema3a expression is needed for sympathetic innervation patterning and is critical for heart rate control.
