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目的探讨高脂喂食诱导的肥胖大鼠肾周脂肪与血压水平的关系以及血管紧张素受体拮抗剂替米沙坦对其的干预作用。方法给予8周龄雄性Wistar大鼠高脂喂食12周,建立肥胖大鼠模型。肥胖大鼠随机分为高脂组和干预组(n=7),分别给予高脂饲料和高脂饲料+替米沙坦8mg/(kg·d)。另取体质量、周龄匹配雄性Wistar大鼠为空白组(给予标准大鼠饲料)和对照组[标准大鼠饲料+替米沙坦8mg/(kg·d)],每组7只。每周称重并采用无创尾动脉测压法监测大鼠血压。药物干预20周后,颈动脉插管测得血压,并测定大鼠体质量、肾周脂肪质量、血脂、血糖和胰岛素水平,血浆及肾周脂肪组织血管紧张素Ⅱ(AngⅡ)、醛固酮水平,并检测肾周脂肪血管紧张素Ⅱ1型受体(AT1R)水平。结果实验结束时高脂组大鼠体质量、收缩压及舒张压高于空白组(均P<0.05)。且高脂组肾周脂肪相对质量[(0.46±0.02)比(0.14±0.01)g/100g]、血浆AngⅡ水平[(2360.0±380.7)比(1697.9±360.7)ng/L]、肾周脂肪AT1R蛋白及mRNA水平高于空白组(均P<0.05)。与高脂组比较,干预组肥胖大鼠的体质量及肾周脂肪质量、收缩压及舒张压水平降低,血浆AngⅡ水平减少,肾周脂肪局部肾素血管紧张素醛固酮系统(RAAS)组分降低(均P<0.05)。相关性分析发现大鼠肾周脂肪相对质量与收缩压和舒张压呈正相关(分别r=0.773和0.673,均P<0.01)。大鼠体质量与收缩压呈正相关(r=0.628,P<0.01),与舒张压无相关(r=0.214,P>0.05)。多元逐步回归分析结果表明,体质量(β=0.287)、肾周脂肪相对质量(β=0.405)、肾周脂肪AngⅡ水平(β=0.324)、血浆AngⅡ水平(β=0.721)及醛固酮水平(β=0.305)是大鼠收缩压的影响因素(均P<0.05),血浆AngⅡ水平(β=0.529)、肾周脂肪相对质量(β=0.413)、肾周脂肪AngⅡ水平(β=0.257)是大鼠舒张压的影响因素(均P<0.05)。结论替米沙坦可通过减少肾周脂肪堆积,抑制其局部RAAS,改善肥胖相关的血压异常。
Objective To investigate the relationship between perirenal fat and blood pressure in obese rats fed with high-fat diet and the intervention of angiotensin Ⅱ receptor antagonist telmisartan. Methods Eight-week-old male Wistar rats were fed with high-fat diet for 12 weeks to establish an obese rat model. Fat rats were randomly divided into high-fat group and intervention group (n = 7), and were given high fat diet and high fat diet + telmisartan 8mg / (kg · d) respectively. Another body weight, age-matched male Wistar rats were blank group (given standard rat feed) and control group [standard rat feed + telmisartan 8mg / (kg · d)], 7 in each group. Weekly weighed and noninvasive tail arterial manometry was used to monitor rat blood pressure. Twenty weeks after the drug intervention, blood pressure was measured by carotid artery cannulation. Body mass, peri-renal fat mass, blood lipids, blood glucose and insulin levels, plasma and perirenal adipose tissue angiotensin II (Ang II), aldosterone level, Peripheral fat angiotensin Ⅱ type 1 receptor (AT1R) levels were measured. Results At the end of the experiment, the body weight, systolic pressure and diastolic blood pressure in hyperlipidemic rats were higher than those in the blank group (all P <0.05). (0.46 ± 0.02) g / 100g], plasma AngⅡ level [(2360.0 ± 380.7) vs (1697.9 ± 360.7) ng / L], perirenal fat AT1R The protein and mRNA levels were higher than those in the blank group (all P <0.05). Compared with the high-fat group, body weight, peri-renal fat mass, systolic blood pressure and diastolic blood pressure were decreased, plasma AngⅡ level was decreased, and the local renin angiotensin aldosterone system (RAAS) component was decreased (All P <0.05). Correlation analysis showed that the relative peritoneal fat mass was positively correlated with systolic and diastolic pressure (r = 0.773 and 0.673, respectively, P <0.01). There was a positive correlation between body weight and systolic pressure (r = 0.628, P <0.01) and no correlation with diastolic pressure (r = 0.214, P> 0.05). The results of multivariate stepwise regression analysis showed that body mass (β = 0.287), relative weight of perirenal fat (β = 0.405), perirenal fat AngⅡ (β = 0.324), plasma AngⅡ (β = 0.721) and aldosterone = 0.305) were the influencing factors of systolic blood pressure (P <0.05), plasma AngⅡ level (β = 0.529), relative perirenal fat mass (β = 0.413) and perirenal fat AngⅡ The influencing factors of rat diastolic pressure (all P <0.05). Conclusion Telmisartan can improve the obesity-related abnormal blood pressure by reducing the accumulation of perirenal fat and inhibiting its local RAAS.