宫内生长受限大鼠肝脏组蛋白H3乙酰化的研究

Acetylation of hepatic histone H3 in rats with intrauterine growth retardation

摘要:

目的：研究孕期营养不良造成的宫内生长受限(intrauterine growth retardation，IUGR)大鼠肝脏中组蛋白H3的乙酰化水平，以及组蛋白去乙酰化酶1 (histonedeacetyl-ases，HDAC1)的表达变化，探讨两者之间的相互联系。方法：采用孕期全程低蛋白饮食法建立大鼠IUGR模型，分离成年雄性子鼠（8周）的肝脏，采用荧光定量RT-PCR技术检测肝脏中HDAC1的mRNA表达，Western blot方法检测肝细胞核中HDAC1的蛋白含量，以及组蛋白H3/K9的乙酰化水平。结果：IUGR组HDAC1的mRNA水平仅是对照组的54%（t=2.042，P＜0.05），肝细胞核中的HDAC1蛋白表达同样明显低于对照组(438±47 vs 1 128±110)（t=2.179，P＜0.05）。与之相反，与对照组（10.5±1.2）%相比，IUGR大鼠肝脏中乙酰化的H3/K9占总H3组蛋白的百分比（17.3±1.6）%明显增高（t=3.597，P＜0.01），且核中的HDAC1蛋白水平与H3/K9乙酰化水平明显负相关（r=-0.781，P＜0.01）。结论：IUGR大鼠肝细胞核中HDAC1蛋白表达降低，引起组蛋白H3的乙酰化水平增高，染色质的表观遗传学变化可能是肝脏某些基因转录调控变化的分子基础。［中国当代儿科杂志，2009，11（9）：753-756］

Abstract:

OBJECTIVE: To investigate the effects of intrauterine growth retardation (IUGR) caused by malnutrition during pregnancy on the acetylation of histone H3 and expression of histonedeacetylase1(HDAC1) in the hepar of the adult offspring and to explore the relationship between them. METHODS: Male 8-week-old offspring from maternal protein-malnutrition dams were studied. The expression of HDAC1 mRNA in the hepar was measured by fluorescent quantization RT-PCR. The levels of hepatic nuclear HDAC1 protein and acetylation of histone H3/K9 were assessed by Western blot. RESULTS: The hepatic HDAC1 mRNA expression in IUGR rats was reduced to 54% of that of normal control rats (t=2.042, P<0.05). A decline in nuclear expression of HDAC1 protein (438±47) was also noted when compared with normal controls (1 128±110)(t=2.179, P<0.05). In contrast, the percentage of acetylated histone H3/K9 in IUGR rats (17.3±1.6%) increased significantly compared with that of normal control rats (10.5±1.2%) (t=3.597, P<0.01). The level of acetylated histone H3/K9 was negatively correlated with the HDAC1 protein concentration (r=-0.781, P<0.01). CONCLUSIONS: Increased hepatic acetylation of histone H3 in the IUGR offspring might be caused by decreased HDAC1 expression in nuclear protein. This may contribute to the transcription change of some genes in the hepar.［Chin J Contemp Pediatr, 2009, 11 (9):753-756］