日本一個研究小組經(jīng)動物實驗證實,，一種阻礙神經(jīng)再生的蛋白質(zhì)出現(xiàn)異?？梢l(fā)心律不齊,，從而導致猝死,。
由慶應義塾大學,、札幌醫(yī)科大學和名古屋大學等組成的研究小組在９日《自然·醫(yī)學》網(wǎng)絡版上發(fā)表論文說,，蛋白質(zhì)“ｓｅｍａｐｈｏｒｉｎ－３ａ”合成量不足或過量都會使心臟交感神經(jīng)的分布形式發(fā)生異常,，導致心臟電活動不穩(wěn)定，從而引發(fā)致命的心律不齊,。
心臟的搏動頻率由交感神經(jīng)調(diào)節(jié),。研究人員通過基因技術(shù)，使實驗鼠體內(nèi)不能生成上述蛋白質(zhì),，之后檢查實驗鼠心臟，發(fā)現(xiàn)交感神經(jīng)的分布無序,。這種實驗鼠有８０％出生不到１周就會死亡,。研究人員對幸存下來的老鼠進行研究發(fā)現(xiàn),，它們的心律不齊,，心跳有時會突然停止。
另外,，研究人員還培養(yǎng)了一些可以過量分泌“ｓｅｍａｐｈｏｒｉｎ－３ａ”蛋白質(zhì)的實驗鼠，發(fā)現(xiàn)它們的心臟交感神經(jīng)大量減少,，出生８周以后,，心跳異常,、猝死的傾向比較明顯。
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 [email protected]
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.
