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生长抑素和细胞凋亡在围产期及婴儿不明原因猝死呼吸控制中的作用

Role of somatostatin and apoptosis in breathing control in sudden perinatal and infant unexplained death.

作者信息

Lavezzi A M, Ottaviani G, Matturri L

机构信息

Lino Rossi Research Center for the Study and Prevention of Unexpected Perinatal Death and Sudden Infant Death Syndrome, Institute of Pathology, University of Milan, Italy.

出版信息

Clin Neuropathol. 2004 Nov-Dec;23(6):304-10.

Abstract

OBJECTIVES

To obtain basic information about the expression of somatostatin in the human central nervous system and, in particular, to evaluate its possible involvement in unexplained perinatal and in sudden infant death syndrome.

MATERIAL

Sixty-seven brainstems from subjects aged from 30 gestational weeks to 12 postnatal months, dying of both known and unknown causes, were selected for this study. The unexplained deaths included 17 sudden intrauterine deaths, 5 sudden neonatal deaths and 28 sudden infant deaths.

METHOD

All brainstems were fixed in 10% phosphate-buffered formalin, processed and embedded in paraffin, according to our protocol available on the web site: http://users.unimi.it/-pathol/sids/riscontro_diagnostico_e.html. The distribution of the somatostatin in the brainstem was studied by immunohistochemistry on serial sections.

RESULTS

We observed an intense somatostatin positivity in many brainstem nuclei prevalently involved in the respiratory activity (parabrachial/Kölliker-Fuse complex, locus coeruleus, hypoglossus nucleus, dorsal vagus motor nucleus, tractus solitarii nucleus, ambiguus nucleus, reticular formation) in stillbirths. In 10 fetuses with unexplained death the neurons of the hypoglossus nucleus were somatostatin-negative. In the postnatal deaths, we observed immunopositivity in the ventrolateral and ventral subnuclei of the tractus solitarii nucleus. Besides, in 15 sudden infant death victims and in 1 control case, somatostatin-positive neurons were also present in the hypoglossus nucleus. In 10 of these 15 cases, a high apoptotic index was also reported.

CONCLUSIONS

We suggest that abnormalities in the distribution of SS in the hypoglossus nucleus before and after birth may contribute to the induction of both fatal breathing in prenatal life and abnormal ventilatory control after birth leading to irreversible apnea.

摘要

目的

获取有关生长抑素在人类中枢神经系统中表达的基础信息,尤其是评估其可能与不明原因围产期死亡及婴儿猝死综合征的关联。

材料

选取67例年龄从孕30周至出生后12个月、死于已知和未知原因的脑干用于本研究。不明原因死亡包括17例宫内猝死、5例新生儿猝死和28例婴儿猝死。

方法

所有脑干均按照我们网站(http://users.unimi.it/-pathol/sids/riscontro_diagnostico_e.html)上的方案,固定于10%磷酸盐缓冲福尔马林中,进行处理并石蜡包埋。通过对连续切片进行免疫组织化学研究脑干中生长抑素的分布。

结果

我们观察到,死产儿中许多主要参与呼吸活动的脑干核(臂旁/柯利克 - 富斯复合体、蓝斑、舌下神经核、迷走神经背运动核、孤束核、疑核、网状结构)中有强烈的生长抑素阳性。在10例不明原因死亡的胎儿中,舌下神经核的神经元生长抑素呈阴性。在出生后死亡病例中,我们在孤束核的腹外侧和腹侧亚核中观察到免疫阳性。此外,在15例婴儿猝死受害者和1例对照病例中,舌下神经核中也存在生长抑素阳性神经元。在这15例中的10例中,还报告了高凋亡指数。

结论

我们认为,出生前后舌下神经核中生长抑素分布异常可能导致产前致命性呼吸以及出生后异常通气控制,进而导致不可逆的呼吸暂停。

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