肛门直肠畸形大鼠泄殖腔胚胎发育过程中细胞凋亡的研究

Relationship between glucocorticoid receptors and glucocorticoid resistance in children with idiopathic thrombocytopenia purpura

摘要:

目的:肛门直肠正常胚胎发育过程中，细胞凋亡发挥重要作用。该研究调查了肛门直肠畸形(anorectal malformation, ARM)胎鼠泄殖腔胚胎发育过程中细胞凋亡情况，以了解ARM胚胎发育过程中细胞凋亡的作用。方法:在胚胎发育的第10天，通过胃管注入乙烯硫脲（125 mg/kg）致畸孕鼠，诱导ARM 胚胎。在胚胎发育的第13，13.5，14，15和16天，利用苏木素-伊红和TUNEL染色技术检测正常对照胚胎 (n=102) 和 ARM 胚胎 (n=147) 泄殖腔凋亡细胞的分布。结果:对照组胚胎第13天尿直肠隔可见凋亡细胞，随着胚胎发育，尿直肠隔间质内的凋亡细胞逐渐增多；直肠背侧间质可见大量凋亡细胞。胚胎第14天，直肠末端和未来肛门开口处的泄殖腔膜开始出现凋亡细胞。胚胎第15天，尿直肠隔与泄殖腔膜融合，尿直肠隔间质内的凋亡细胞一直向下延伸到融合部位。ARM胎鼠与对照组胎鼠相比，在胚胎发育过程中尿直肠隔间质、直肠背侧间质和泄殖腔膜的凋亡细胞均明显减少。ARM胎鼠尿直肠隔的发育明显延迟，未与泄殖腔膜融合。结论:在泄殖腔的胚胎发育过程中，尿直肠隔间质、直肠背侧间质和泄殖腔膜细胞凋亡的异常是导致ARM的原因之一。细胞凋亡的正常调控是保证肛门直肠胚胎期正常发育的关键机制之一。［中国当代儿科杂志，2009，11（9）：709-713］

Abstract:

OBJECTIVE: To identify the relationship between the expression of α and β-isoforms of glucocorticoid receptors (GR) in peripheral blood mononuclear cells (PBMC) and glucocorticoid resistance in children with idiopathic thrombocytopenia purpura (ITP). METHODS: Real-time PCR was used to detect the expression of GRα and GRβ mRNA in PBMC from 30 children with ITP (glucocorticoid-sensitive, n=18; glucocorticoid-resistant, n=12) and 10 healthy children (control group). Enzyme immunoassay was used to measure plasma levels of total glucocoticoits. RESULTS: There were no significant differences in PBMC GRα mRNA levels among the glucocorticoid sensitive, the glucocorticoid-resistant and the control groups. Compared with the glucocorticoid-sensitive and the control groups, the expression of GRβ mRNA in the glucocorticoid-resistant group was significantly up-regulated (P<0.01). Plasma total glucocoticoits level in the glucocorticoid-resistant group was found to be much higher than that in the glucocorticoid-sensitive and the control groups (P<0.01). CONCLUSIONS: The up-regulated expression of GRβ mRNA may associated with glucocorticoid resistance in children with ITP.［Chin J Contemp Pediatr, 2009, 11 (9):714-716］