高脂喂食诱导的肥胖大鼠肾周脂肪功能与肾损害的关系及替米沙坦干预的影响  

Relationship between the function of perirenal adipose tissue and renal injury and the interventional effect of telmisartan in obese rats induced by a high-fat diet

作　　者：李昊[1] 王亚萍[2] 宋艳[3] 张恒[4] 李敏[4] 索萌[5] 高兰[1] 田刚[4] 

机构地区：[1]西安交通大学医学院第一附属医院重症医学科,陕西西安710061 [2]陕西省人民医院心血管内三科 [3]西安交通大学医学院第一附属医院超声科 [4]西安交通大学医学院第一附属医院心血管内科 [5]山东省立医院麻醉科

出　　处：《中华高血压杂志》2015年第11期1053-1061,共9页Chinese Journal of Hypertension

基　　金：国家自然科学基金项目(30871042);陕西省科学技术研究发展计划国际科技合作与交流计划项目(2012kw-40-01);陕西省科学技术研究发展计划自然科学基础研究计划项目(2014JM2-8145)

摘　　要：目的探讨高脂喂食诱导的肥胖大鼠肾周脂肪与肾脏病变的关系及替米沙坦干预的影响和可能作用机制。方法给予20只8周龄雄性Wistar大鼠高脂喂食12周,另取体质量、周龄匹配雄性Wistar大鼠20只,给予普通喂食12周。高脂喂食大鼠中肥胖大鼠造模成功14只,随机分为高脂组(n=7)和高脂治疗组(n=7),分别给予高脂喂食和高脂+替米沙坦8mg/(kg·d)。普通喂食的Wistar大鼠中抽取14只分为普食组(给予标准大鼠饲料)和普食治疗组[标准大鼠饲料+替米沙坦8mg/(kg·d)],每组7只。替米沙坦干预20周后,比较各组大鼠肾功能(尿素氮、肌酐及尿蛋白),同时行肾脏组织切片及苏木素伊红并过碘酸雪夫染色,比较各组大鼠肾脏病理积分;利用Western blot方法检测各组大鼠肾周脂肪组织过氧化物酶体增殖物激活受体γ(PPAR-γ)、脂肪细胞型脂肪酸结合蛋白(aP2)、瘦素及脂联素表达水平;酶联免疫吸附试验检测各组大鼠肾周脂肪组织肿瘤坏死因子(TNF)α表达水平;Real-time聚合酶链反应检测各组大鼠肾周脂肪组织单核细胞趋化蛋白1(MCP-1)及白细胞介素6(IL-6)表达水平。并用各组大鼠肾周脂肪组织制备条件培养基,利用条件培养基培养肾小球内皮细胞及系膜细胞,四甲基偶氮唑盐比色法(MTT)检测细胞增殖情况。结果在32周的实验终点,与普食组相比,高脂组大鼠尿素氮[(20.73±1.29)比(6.36±0.33)mmol/L]、肌酐[(145.32±5.98)比(68.42±4.77)μmol/L]、24h尿蛋白[(312.74±5.51)比(30.14±2.15)mg]增高(均P<0.05)。高脂组大鼠肾周脂肪组织PPAR-γ及aP2表达下降,伴随脂联素表达下降,瘦素、TNF-α、MCP-1及IL-6表达上升(均P<0.05);替米沙坦干预后,刺激PPAR-γ及aP2表达,升高脂联素,降低瘦素、TNF-α、MCP-1及IL-6表达(均P<0.05)。体外实验方面,和普食组大鼠肾周脂肪制备的条件培养基相比,高脂组大鼠肾周脂肪制备的条件培养基培养的肾小球内皮细胞及系�Objective To investigate the relationship between the function of perirenal adipose tissue and renal injury and the interventional effect of telmisartan in obese rats induced by high-fat diet, and to explore the underlying mechanisms. Methods 8 weeks old male Wistar rats （n=20） were fed with high-fat diet for 12 weeks to establish obese rat model. Age and weight-matched male Wistar rats （n=20） were fed with standard diet for 12 weeks as controls. A total of 14 obese rat models were established and were randomly divided into high fat diet group （ n= 7） , and high fat plus treatment group [high fat diet±telmisartan 8 mg/（kg · d） , n=7]; male Wistar rats fed with standard diet were also divided into standard diet group （standard diet, n = 7 ） and standard diet plus treatment group [standard diet-telmisartan 8 mg/（kg · d）, n= 7]. Telmisartan intervention was carried out for 20 weeks. By the end of the experiment, renal function including the levels of serum urea nitrogen, creatinine and urinary protein, and kidney pathological score （hematoxylin-eosin and periodic acid-Schif{ staining） were examined. In perirenal adipose tissue, the expression levels of peroxisome proliferator activated receptor-γ （PPAR-γ）, adipocyte fatty acid binding protein （aP2）, leptin and adiponectin were detected by Western blot, the expression of tumor necrosis factor-α （TNF-α） by enzyme linked immunosorbent assay（ ELISA）, and mRNA levels of monocyte chemoattractant protein-1 （MCP-11 and interleukin-6 （IL-6} hy real-time polymerase chain reaction（PCR）. Glomerular endothelial ceils （GECs） and glomerular mesangial cells （GMCs） were cultured with perirenal adipose tissue-conditioned medium, and methyl thiazolyl tetrazolium （MTT） method was used to determine cell proliferation. Results Compared to the standard diet group, the levels of serum urea nitrogen [ （ 20.73 ± 1.29 ） vs （ 6.36 ±0.33 ） mmol/L], creatinine [（145.32 ±5.98） vs （68.42±4.77）μmol/L], 24 h

关 键 词：肥胖 肾周脂肪 替米沙坦 肾损害 

分 类 号：R589.2[医药卫生—内分泌] R692[医药卫生—内科学]