孕期摄食限制对雌性子代老年大鼠代谢综合征易感的影响

Prenatal food restriction-induced increasing susceptibility to metabolic syndrome in aged female offspring rats

目的探讨孕期摄食限制(prenatal food restriction,PFR)的雌性子代老年大鼠在经历体重追赶性生长和后期慢性应激后的代谢综合征(metabolic syndrome,Met S)易感现象及其可能的发生机制。方法将受孕的SPF级Wistar大鼠随机分为对照组和PFR组,每组18只。自孕11 d起至分娩,PFR组限制摄食(为对照组每日食物的50%),对照组自由饮食至自然分娩。分娩后每组筛选出窝仔数为10~12只的母鼠9窝,每窝随机抽取1只雌性仔鼠。仔鼠断乳后均给予高脂饮食至成年,出生后38周龄给予两周的预知性慢性应激,并采集应激前后仔鼠血清。以放射免疫法检测血清促肾上腺皮质激素(adreno-cortico-tropic-hormone,ACTH)和胰岛素水平,酶联免疫吸附法检测血清皮质酮(corticosterone,CORT)浓度,酶比色法检测血糖、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白-胆固醇(high-density lipoprotein,HDL-C)和低密度脂蛋白-胆固醇(low-density lipoprotein,LDL-C)浓度。结果与对照组相比,PFR组子代大鼠出生后体重偏低,但其出生后16~36周体重增长率升高。应激前,PFR组血清胰岛素、HDL-C水平降低,TC/HDL-C比值升高;应激后,PFR组血清ACTH无明显改变,CORT水平升高,血清胰岛素水平降低,血清TG水平和TG/HDL-C比值升高,差异均有统计学意义(P<0.05或P<0.01)。结论出生后早期经历追赶性生长的PFR雌鼠存在糖脂代谢紊乱及Met S易感,其发生可能与下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal axis,HPA)轴相关的神经内分泌代谢编程紊乱有关。

Objective To verify that aged female rats that had experienced PFR and ＂catch-up growth＂ have increased susceptibility to adult metabolic syndrome （MetS）. Methods Pregnant rats were randomly divided into the control and PFR groups, 18 in each. Maternal rats were fed restricted diet from gestational day 11 to delivery, litters with 10-12 pups were included in the experiment （nine litters each group）. One female pup was randomly selected from each litter in the control and PFR groups （nine pups each group, n=9）. All pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks （PW） 38-40. Blood was collected before and after UCS. Serum adreno-cortieo-tropic- hormone （ACTH） and insulin were determined by radioimmunoassay, serum cortieosterone （CORT） was measured by enzyme linked immunosorbent assay （ELISA）. Serum glucose, total cholesterol （TC）, triglyeeride （TG）, high-density lipoprotein- cholesterol （HDL-C） and low-density lipoprotein （LDL-C） concentrations were all measured by enzymatic colorimetry. Results Compared with the control group, PFR group resulted in the reduced bodyweight, but the higher weight gain rate. Before UCS, serum insulin and HDL-C levels were decreased significantly （P〈0.05, P〈0.01）, while the ratio of TC/HDL-C was increased in the PFR group （P〈0.05）. After UCS, serum ACTH level remained unchanged but CORT level significantly elevated （P〈0.01）. Moreover, serum insulin level was still decreased （P〈0.05）, while serum TG level and the ratio of TG/HDL remarkably raised compared with the control （P〈0.01, P〈0.05）. Conclusion Aged female offspring rats of PFR that have experienced catch-up growth display increasing susceptibility to MetS and its underlying mechanism may be related with the disorder of hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendoerine metabolic programming.