高脂高盐饮食诱导巴马小型猪高血压模型的建立及其机制探讨  

Establishment of a Bama minipig model of hypertension induced by high fat and high salt diet and its mechanism

作　　者：戎亦骊 潘永明[1] 黄俊杰 徐孝平[1] 朱科燕[1] 陈方明[1] 陈民利[1] RONG Yili;PAN Yongming;HUANG Junjie;XU Xiaoping;ZHU Keyan;CHEN Fangming;CHEN Minli(Laboratory/Animal Research Center/Comparative Medical Research Institute,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学动物实验研究中心/比较医学研究所,杭州310053

出　　处：《中国实验动物学报》2018年第4期474-479,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：浙江省科技厅公益性(No.2017C37110)~~

摘　　要：目的采用高脂高盐饮食建立巴马小型猪高血压模型,并探讨其可能的发病机制。方法取雄性巴马小型猪18只,随机分成3组:正常对照(NC)组、高脂(HF)组和高脂高盐(HFHS)组,每组6只。NC组饲喂普通饲料,HF组和HFHS组分别饲喂高脂饲料和高脂高盐饲料,连续24周。在造模8周、16周和24周时测量小型猪的收缩压(SBP)和舒张压(DBP),在造模24周时测定血糖血脂和肝肾功能,以及血浆内皮素1(ET-1)、肾素(Renin)、血管紧张素II(Ang II)、水通道蛋白-2(AQP-2)、血管加压素(AVP)和血管内皮生长因子(VEGF)等指标,并取肝、肾进行组织病理学观察。结果与NC组比,HF组和HFHS组在造模8周后SBP和DBP明显升高,并呈持续上升趋势,且HFHS组高于HF组;同时,造模24周后HF组和HFHS组小型猪的体重和肝、肾指数均显著增加(P<0.05),且血浆TC、CREA和ET-1水平亦显著升高(P<0.05,P<0.01);而HFHS组BUN水平显著降低(P<0.05),但renin、Ang-II、AQP-2、AVP含量均显著升高(P<0.05,P<0.01)。油红"O"染色结果显示,HF组和HFHS组肝、肾出现脂质沉积,且出现肾小动脉管壁增厚等病理改变。结论高脂高盐饮食诱导8周可建立小型猪高血压模型,其发病机制可能与影响肾脏功能进而激活RAS系统和AVP-AQP-2有关。Objective To establish a Bama minipig model of hypertension induced by high-fat and high-salt diet and to explore its mechanism. Methods Eighteen healthy male Bama minipigs were randomly divided into 3 groups：normal control（ NC） group,high-fat（ HF） diet group and high-fat/high-salt diet（ HFHS） group,6 in each group. The NC group was fed normal basal diet,the HF group and HFHS group were fed with high-fat diet and high-fat/high-salt diet for 24 weeks,respectively. The systolic blood pressure（ SBP） and diastolic blood pressure（ DBP） were measured at 8,16 and 24 weeks of modeling. The minipigs were weighed and the levels of blood glucose,lipids,liver and kidney function as well as the levels of endothelin-1（ ET-1）,renin,angiotensin II（ Ang-II）,aquaporin-2（ AQP-2）,vasopressin（ AVP） and vascular endothelial growth factor（ VEGF） were determined at 24 weeks after modeling. Meanwhile,samples of liver and kidney tissues were taken for histopathological examination. Results Compared with the NC group,SBP and DBP were significantly increased in the HF and HFHS groups after 8 weeks of modeling and showed a continuous rising trend,and the HFHS group was higher than that in the HF group. The body weight and liver and kidney coefficients were significantly increased in the HF and HFHS groups（ P 〈0. 05）,and levels of plasma TC,CREA and ET-1 were significantly increased（ P 〈0. 05,P 〈0. 01）. In addition,the level of BUN was significantly decreased（ P 〈0. 05）and the levels of renin,Ang-II,AQP-2 and AVP in the HFHS group were significantly increased（ P 〈0. 05,P 0. 01）. Oil red ＂O＂staining showed lipid deposition in the liver and kidney tissues,and thickening of renal arterial wall and other pathological changes in the HF and HFHS groups. Conclusions A Bama minipig model of hypertension is successfully established by high fat and high salt diet for 8 weeks. Its pathogenesis may be related to the effect of alteration in renal function and activation of RAS system

关 键 词：高脂高盐饮食 高血压 小型猪 肾素-血管紧张素系统 水通道蛋白2 

分 类 号：Q95-33[生物学—动物学]