骨形态发生蛋白4在内耳发育及在毛细胞与螺旋神经节细胞再生中的研究进展

听力损失是人类最常见的感觉缺陷,主要涉及到毛细胞(HCs)和螺旋神经节细胞(SGCs)的损失等。在内耳发育过程中,骨形态发生蛋白4(BMP4)的表达具有时序性和特异性,并且通过调控分泌蛋白Tsukushin(TSK)、性别决定相关基因簇2蛋白(SOX2)等细胞因子,与WNT和SHH等信号通路之间相互作用,参与耳泡的诱导、前庭和耳蜗等器官的形成、HCs和SGCs等细胞的分化过程。此外,近些年在哺乳动物与非哺乳动物的耳蜗外植体中,发现BMP4在HCs和SGCs的再生中起重要作用。综述BMP4调控内耳发育、诱导HCs和SGCs再生的作用,以及相关的研究进展,以期为HCs和SGCs再生相关机制的阐明奠定基础,为听力损失的治疗带来新的思路与策略。     

Ototoxic mechanisms: A Working Hypothesis

The effect of the ototoxic aminoglycosidic antibiotics, including neomycin, gentamicin and other members of the streptomycin family, on the internal ear is well known. In the cochlea, it has been generally interpreted as a direct toxic action on the sensory cells of the spiral organ. Measurements of antibiotic levels in the internal ear fluids have indicated a gradual build-up of concentrations that persist for some time after the plasma level has fallen to zero.

The existence of a 'blood-ear' (hemato-laby-rinthine) barrier is suggested, corresponding to but less effective than the blood-brain barrier. The barrier must depend, inter alia, upon the integrity of the spiral ligament and the stria vascularis and their microvaculature. Evidence is presented to show that the aminoglycosides damage these 'secretory' tissues as well as those of the spiral prominence and outer sulcus, which are believed to be reabsorptive in function. The ototoxic process is thought to correspond to the nephrotoxic action, which occurs mainly in the renal tubules. Injury to the sensory cells is regarded as secondary to the disruption of the micro-homeostatic mechanism of the cochlea which maintain the appropriate concentrations of sodium and potassium ions in the endolymph and perilymph. The aminoglycosidic antibiotics are presumably bound to the proteins of the tissues affected, but understanding of the nature of the metabolic reactions inhibited remains for future cytochemical research.     

Ngn2和Math6在小鼠内耳不同时期表达的初步研究

目的研究neurogenin2(ngn2)和math6在不同时期小鼠内耳的表达变化,并初步探讨其对螺旋神经元发育的调控作用。方法本实验选取不同时期健康的BALB/c小鼠,以E12.5、E13.5、E14.5、E17.5、P1、P7和成年为观察时间点,应用real-time PCR、免疫组织化学方法检测ngn2、math6在耳蜗中mRNA和蛋白的表达。结果 (1)re al-time PCR结果提示ngn2在E12.5d呈高表达,随后在E13.5d表达量下调,直至成年呈低水平表达;math6在E12.5-P1都呈较高水平表达,其中在P1达到高峰,随后于P7至成年表达量下调。(2)免疫组织化学结果提示,在E13.5、E14.5和P1,ngn2和math6在螺旋神经节处(或螺旋神经元细胞核处)有不同程度的阳性表达;在成年期,math6在细胞核有弱表达,但ngn2几乎不表达,各组间差异有统计学意义(P<0.05)。结论 (1)ngn2在E12.5d表达呈高峰,提示其在有增殖能力的神经祖细胞中起作用;math6在E12.5d-P1呈高表达,提示其在神经祖细胞的增殖以及分化中其起重要作用;(2)ngn2和math6在耳蜗中表达的空间和时间模式的重叠和差异,提示它们在调控通路中可能受到共同的分子调控。