摘要
目的观察出生后过度营养及高脂饮食对大鼠血压的影响，探讨哺乳期及早期持续过度营养导致高血压发生发展的病理生理机制。方法应用小窝鼠模型，SD大鼠雄仔出生3d后按随机数字表法分为哺乳期正常营养组（10只／窝）和哺乳期过度营养组（3只／窝）。3周断乳后，再分别按随机数字表法完全随机分组给予标准饲料和高脂饲料至16周；共分为4组：正常营养组、哺乳期过度营养组、断乳后过度营养组、持续过度营养组。每周监测体质量，于3、16周测定大鼠内脏脂肪质量、收缩压及心率。取大鼠胸主动脉行血管内皮舒张功能测定。HE染色观察血管组织形态；硝酸还原法检测血管组织中一氧化氮，实时定量-PCR测定血管内皮型一氧化氮合酶（eNOS）mRNA表达，Western blot法检测其总蛋白及磷酸化蛋白表达水平。结果出生后3周哺乳期过度营养组大鼠体质量[（77．80±0．57）g比（62．80±0．85）g，t=14．576，P〈0．01]、脂肪质量[腹膜后：（8．19±0．49）mg／g比（4．92±0．31）mg／g，t=5．629，P〈0．01；生殖周：（3．50±0．29）mg／g比（2．08±0．13）mg／g，t=4．552，P〈0．01]显著高于正常营养组大鼠；血管组织中磷酸化-eNOS的蛋白表达明显下降并持续到16周（F=15．215，P〈0．01）；断乳后高脂喂养增加哺乳期过度营养组大鼠体质量、脂肪质量。至16周时，持续过度营养组出现高血压[（149±1．94）mmHg（1mmHg=0．133kPa），F=22．834，P〈0．01]、血管内皮舒张功能受损（F=7．648，P〈0．05）及磷酸化-eNOS的蛋白表达下降（F=15．215，P〈0．01），而断乳后过度营养组仅出现血压改变。结论哺乳期过度营养断乳后高脂饮食可导致高血压，血管组织磷酸化eNOS表达的持续下降可能是哺乳期过度营养诱导成年期血管内皮舒张功能紊乱发生的重要分子机制。
Objective To study the effects of postnatal overfeeding and high-fat diet on blood pressure of rats, and to explore the pathophysiological mechanism underlying hypertension induced by continuous early postnatal overfeeding. Methods Male Sprague-Dawley rats were randomly divided into normal feeding group （10/litter） and overfeeding group （3/litter） on postnatal day 3 with a random number table. After weaning at postnatal week 3, the rats were randomly given standard chow or high-fat （HF） diet until week 16. Hence four groups were analyzed, namely normal feeding group, breastfed overfeeding group, post-weaning overfeeding group, and continuous overfeeding group. Body weight was continuously monitored in each week. Visceral fat pad （retroperitoneal and perigenital）, systolic pressure, and heart rate were observed at week 3 and week 16. Thoracic aorta was sampled for measurement of vascular endothelial dilation function. Histological morphology was observed with HE staining, nitric oxide content of thoracic aorta was detected with nitrate reductase method. The mRNA expression of endothelial nitric oxide synthase （eNOS） in thoracic aorta was determined by real-time polymerase chain reaction. The protein expressions of eNOS and phosphorylated eNOS were determined by Western blot. Results At week 3, breasffed overfeeding rats displayed significantly larger body weight [ （77.80 ± 0. 57） g vs. （62. 80 ±0. 85 ） g, t = 14. 576, P 〈 0. 01 ] and visceral fat [ retroperitoneal ： （ 8. 19 ± 0. 49） mg/g vs. （4. 92 ± 0.31） mg/g, t=5.629, P〈0.01; perigenital： （3.50 ±0.29） mg/g vs. （2.08 ±0.13） mg/g, t =4.552, P 〈 0. 01 ] compared with normal feedindg rats, and the protein expression of phosphorylated eNOS in aortic tissues was significantly reduced to week 16 （F = 15.215, P 〈 0. 01 ） ; high-fat diet feeding after weaning further increased the body weight and fat mass in breastfed overfeeding rats. At week 16, continuous overfeeding rats showed hypertension [ （ 149
出处
《中华临床营养杂志》
CAS
CSCD
2015年第3期156-163,共8页
Chinese Journal of Clinical Nutrition
基金
国家自然科学基金（81273064）
关键词
哺乳期过度营养
血管内皮舒张功能
高血压
一氧化氮
磷酸化-内皮型一氧化氮合酶
Early postnatal overfeeding
Vascular endothelial dilation function
Hypertension
Nitricoxide
Phosphorylated endothelial nitric oxide synthase
