成纤维细胞生长因子21对胰岛素抵抗所致高血压的治疗作用  

Therapeutic effect of fibroblast growth factor 21 on hypertension induced by insulin resistance

作　　者：朱升龙[1] 任桂萍[1] 张振宇[1] 王文飞[1] 叶贤龙[1] 韩苗苗[1] 赵景壮[1] 徐彤宇[1] 刘铭瑶[1] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院,黑龙江哈尔滨150030

出　　处：《药学学报》2013年第9期1409-1414,共6页Acta Pharmaceutica Sinica

基　　金：黑龙江省发改委项目(黑发改项目[2011]1570号);黑龙江省教育厅科学技术研究项目(12521z004);哈尔滨市科技创新人才研究专项资金项目(2012RFXXS034);黑龙江省高校科技成果产业化前期研发培育项目(1252CGZH29);黑龙江省博士后科研启动基金(LBH-Q09162);国家自然基金东北农业大学生物学理科基地科研训练及科研能力提高项目(J1210069/J0106)

摘　　要：本文研究考察成纤维细胞生长因子21(FGF21)对果糖诱导的胰岛素抵抗高血压模型的治疗作用及其机制。10%果糖诱导SD大鼠4周建立胰岛素抵抗高血压模型,成模后随机分为4组:模型对照组及FGF210.25、0.1和0.05μmol·kg-1·d-1剂量组,5只相同周龄的正常SD大鼠作为正常对照组。每天注射1次,治疗4周,给药期间每周监测大鼠体重,采用尾套法检测收缩压变化;口服葡萄糖耐量试验(OGTT)及胰岛素稳态评价模型检测胰岛素抵抗情况;给药结束时留取血清样本分别测定血清胰岛素、血脂、血糖水平。结果显示,治疗4周后,不同剂量FGF21治疗组大鼠收缩压均下降至正常水平[(122.2±3.5)mmHg,P<0.01],而注射生理盐水的模型对照组大鼠的收缩压在治疗期间一直维持在较高水平[(142.5±4.5)mmHg]。24 h观察各组大鼠血压发现,FGF21治疗组大鼠24 h血压基本维持在(130±4.5)mmHg,各时间段血压均显著低于模型对照组[(130±4.5)vs(143±5.5)mmHg,P<0.01]。FGF21治疗组大鼠血脂改善明显,总胆固醇与甘油三酯含量均显著下降至正常水平。FGF21各治疗组大鼠血清NO含量均显著高于模型对照组[(7.32±0.11),(7.24±0.13),(6.94±0.08)vs(6.56±0.19)μmol·L-1,P<0.01],且其改善程度呈现明显的剂量依赖性,表明FGF21可明显升高果糖诱导高血压模型大鼠血清NO含量,改善内皮释放NO功能。OGTT及HOMA-IR结果显示,经FGF21治疗4周后胰岛素抵抗亦明显得到改善,且呈现剂量依赖性。因此本研究揭示了FGF21通过改善胰岛素抵抗,显著降低SD大鼠由于胰岛素抵抗所引起的高血压。这一发现为临床应用FGF21治疗原发性高血压奠定了理论基础。This study is to evaluate the therapeutic effect of fibroblast growth factor 21 （FGF21） on hypertension induced by insulin resistance in rats and to provide mechanistic insights into its therapeutic effect. Male Sprague-Dawley （SD） rats were fed with high-fructose （10%） water to develop mild hypertensive models within 4 weeks, then randomized into 4 groups： model control, FGF21 0.25, 0.1 and 0.05 μmol·kg^-1·d^-1 groups. Five age-matched normal SD rats administrated with saline were used as normal controls. The rats in each group were treated once a day for 4 weeks. Body weight was measured weekly, systolic blood pressure （SBP） was measured noninvasively using a tail-cuff method, insulin sensitivity was assessed using oral glucose tolerance test （OGTT） and HOMA-IR assay. At the end of the treatment, blood samples were collected, and blood glucose, serum cholesterol, serum triglyceride and serum insulin were measured. The results showed that blood pressure of the rats treated with different doses of FGF21 returned to normal levels [（122.2 ±3.5） mmHg, P〈0.01] after 4-week treatment, whereas, SBP of untreated （model control） rats maintained a high level [（142.5 ±4.5） mmHg] throughout the treatment. The observation of blood pressure in 24 h revealed that SBP of FGF21 treated-rats maintained at （130±4.5） mmHg vs （143±5.5） mmHg for model control （P〈0.01）. FGF21 treatment groups improved serum lipids obviously, total cholesterol （TC） and triglyceride （TG） levels decreased significantly to normal levels. The serum NO levels of three different doses FGF21 treatment group were significantly higher than that of the model control group [（7.32 ±0.11）, （7.24±0.13）, （6.94±0.08） vs （6.56±0.19） μmol·L^-1, P〈0.01], and the degree of improvement showed obvious dose-dependent manner, indicating that FGF21 can significant increase serum NO in fructose-induced hypertension rat model and improve endothelial NO release function. The results of OGTT a

关 键 词：成纤维细胞生长因子21 胰岛素抵抗 高血压 果糖 

分 类 号：R963[医药卫生—微生物与生化药学]