p53基因表达对低出生体质量大鼠肾脏功能的影响

摘要

目的：研究p53基因表达对低出生体质量（ LBW）大鼠肾功能的影响。方法将15只孕鼠按随机数字表法分为正常组（5只）、LBW组（5只）和干预组（5只）。正常组母鼠全程以普通饲料（含21％蛋白）喂养；LBW组和干预组大鼠孕期均采用低蛋白饲料（含10％蛋白）喂养。仔鼠出生后母鼠均用普通饲料喂养；干预组母鼠在普通饲料喂养的基础上，于部分饮水中每日添加左旋精氨酸（ L－Arg）200 mg／kg。取7、21 d、2月龄和3月龄仔鼠标本，采用电镜观察肾小球系膜细胞和足细胞超微结构；采用RT－PCR法检查肾脏p53 mRNA的表达水平；留取血、尿标本检测大鼠肾脏功能。结果⑴肾功能比较：3月龄时，LBW组大鼠血尿素氮（ BUN）和尿肌酐（ UCr）和正常组比较差异均有统计学意义（ P ＜0．01）；2月龄时Ccr和正常组相比，LBW组显著降低（ P ＜0．05）；3月龄时LBW组和干预组大鼠Ccr均显著降低（ P ＜0．05）；与正常组相比，3月龄时LBW组和干预组大鼠24 h尿蛋白定量显著增加（ P ＜0．01， P ＜0．05）。⑵3月龄时，与正常组比较，LBW组p53 mRNA表达显著增加；3月龄LBW大鼠p53 mRNA的表达水平与Ccr水平呈负相关（ r ＝－0．91， P ＜0．05）。⑶电镜发现：LBW组肾小球系膜细胞增生伴基质增多、滤过膜足突减少及部分融合；干预组系膜细胞增生较LBW组显著减少。结论 p53基因在LBW大鼠肾组织呈过度表达，LBW大鼠肾功能减退，采用L－Arg干预LBW大鼠肾脏功能有一定程度的改善，提示p53基因参与了LBW大鼠肾功能的损害，也是肾功能减退的原因之一。%Objective To investigate the effect of p53-gene expression on renal function in rat with low birth weight ( LBW) .Methods Fifteen pregnant rats were randomly assigned into normal group, LBW group, and L-arginine ( L-Arg)-treated group.For normal group, pregnant rats were fed with 21% protein diet during pregnancy.For LBW and L-Arg treated groups, rats were fed with 10%protein diet.After de-livery, all rats were fed with 21%protein diet.For L-Arg-treated group, rats were given a supplementation with L-Arg (200 mg/kg) drinking water during 21 d lactation, other rats were given running water.At the age of 2m, the ultrastructural change in mesangial cell and podocyte was observed with electron microscope. At the age of 7 d, 21 d, 2 m, and 3 m old, the p53 mRNA expression in renal tissues was observed with re-verse transcription polymerase chain reaction ( RT-PCR) , blood and urine were collected to detect biochem-ical indicators of renal function and 24 h-urine protein.Results ⑴At the age of 3 m,the blood urea nitro-gen ( BUN) and urine cretinine ( UCr) in normal group were significantly lower than those in LBW group ( P <0.01).Compared to normal group, the Ucr of LBW group was significantly lower at the age of 2 m ( P<0.05).At the age of 3 m,the Ucr of L-Arg treated group and LBW group was significantly lower ( P <0.05), the level of 24 h-Urine protein was notably increased in LBW group and L-Arg treated group than that in normal group ( P <0.01, P <0.05) .⑵At the age of 3 m,the expression of p53 mRNA in LBW group was higher obviously than that in normal group.There is a significantly negative correlation between the expression of p53 mRNA and the level of Ucr in LBW group ( r =-0.91, P <0.05).⑶ There were mesangial cell proliferation with matrix increase, filtration membrane podocyte reduction, and partially dis-solved in LBW group, the mesangial cell proliferation of L-Arg treated group was decreased compared to that in LBW group.Conclusions The higher expression of p53 gene in LBW group might be one of reasons for the decreased renal function in LBW rats.