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中国应用生理学杂志 ›› 2016, Vol. 32 ›› Issue (3): 214-218.doi: 10.13459/j.cnki.cjap.2016.03.006

• 研究论文 • 上一篇    下一篇

儿茶酚抑素在大鼠肾性高血压中的作用及可能机制

丁露, 郑青青, 李洋, 陈宣颖, 陈然, 王雪瑞, 龚永生, 范小芳   

  1. 温州医科大学低氧医学研究所, 浙江 温州 325035
  • 收稿日期:2015-05-28 修回日期:2016-02-17 出版日期:2016-05-28 发布日期:2018-06-12
  • 通讯作者: 范小芳,Tel:0577-86699521;E-mail:fxbwzmc@126.com E-mail:fxbwzmc@126.com
  • 基金资助:
    国家自然科学基金青年项目(81200039);浙江省自然基金项目(LY12H01003 );浙江省教育厅科研项目(Y201326833)

Role of catestatin in 2K1C-induced renal hypertension in rats and the underlying mechanism

DING Lu, ZHENG Qing-qing, LI Yang, CHEN Xuan-ying, CHEN Ran, WANG Xue-rui, GONG Yong-sheng, FAN Xiao-fang   

  1. Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325035, China
  • Received:2015-05-28 Revised:2016-02-17 Online:2016-05-28 Published:2018-06-12
  • Supported by:
    国家自然科学基金青年项目(81200039);浙江省自然基金项目(LY12H01003 );浙江省教育厅科研项目(Y201326833)

摘要: 目的:观察儿茶酚抑素(CST)在两肾一夹(2K1C)肾性高血压大鼠中的表达改变,并初步探讨其对肾性高血压的影响及作用机制。方法:36只SD大鼠随机分为假手术组(Sham)(n=15)和肾性高血压模型组(Model组)(n=21)。Model组采用两肾一夹(2K1C)手术法建立肾性高血压模型,Sham组手术操作同Model组,但不结扎左肾动脉,每周动态监测大鼠尾动脉血压。6周后各组大鼠行颈总动脉插管测定动脉压,Model组再随机分为2K1C组(n=15)与2K1C+CST组(n=6)。2K1C+CST组经颈外静脉一次性给予CST (80 μg/100 g·BW),Sham组与2K1C组给予等容积的生理盐水。各组动物经测血压、采集血标本后被处死,称取左心室加室间隔(LV+S)重量,计算(左心室+室间隔)/体重;高效液相色谱-电化学方法测定血浆中去甲肾上腺素(NE)含量,ELISA法测定血浆CST含量,硝酸还原酶法测定血浆及心室肌一氧化氮(NO)浓度;Western blot法检测延髓、肾上腺髓质、左心室和肾脏的嗜铬蛋白A (Chga)及左心室内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)蛋白表达量。结果:①与Sham组相比,2K1C组大鼠尾动脉压显著升高,左心室明显肥厚(P<0.01);血浆NE含量增高246%(P<0.01),CST水平降低56%(P<0.05);延髓Chga含量增高108%,左心室和肾脏分别降低60%和30%(P<0.05);左心室NO含量增高46%,血浆NO含量增高24%(P<0.05);左心室eNOS、iNOS蛋白表达分别增高66%和40%(P<0.05);②外源性CST显著降低2K1C大鼠颈总动脉压(P<0.05);③与2K1C组相比,2K1C+CST组左心室和血浆NO含量分别增高35%和19%(P<0.05);左心室eNOS蛋白表达高50%(P<0.05),而iNOS表达无显著统计学差异。结论:两肾肾性高血压时大鼠CST表达下调,外源性CST可能通过NO/NOS系统降低肾性高血压的作用,推测CST可能与肾性高血压的发生发展有关。

关键词: 高血压,肾性, 儿茶酚抑素, 一氧化氮, 去甲肾上腺素

Abstract: Objective:To investigate the roles of catestatin (CST) in 2-kidney-1 clip (2K1C)-induced renal hypertension in rats, and to explore the underlying mechanism. Methods:Thirty six male SD rats were randomly divided into Sham group (n=15) and Model group(n=21).The model group was performed by 2K1C operation. For 2K1C operation, the left renal arteries were narrowed by cotton thread. The Sham group was treated with the same condition as the 2K1C group except the renal artery was narrowed. Tail-cuff systemic blood pressure of rats was measured before and every weeks after 2K1C operation. Six weeks after 2K1C operation, a carotid artery catheter was inserted to measure blood pressure of rats under anesthesia. Then, the model group was randomly subdivided into 2K1C group (n=15) and 2K1C+CST group (n=6). The rats of 2K1C+CST group were intravenous given CST (80 μg/100 g) and the rats of Sham or 2K1C group were given normal saline. All rats were sacrificed after blood pressure was measured and blood was collected. Then, the left ventricular plus interventricular septum weight (LV+S) was weighted and the ratio of (LV+S)/body weight(BW) was calculated as the index of left ventricular hypertrophy. Norepinephrine (NE) contents in plasma were determined by high performance liquid chromatography(HPLC) and CST contents in plasma by ELISA. The nitrite/nitrate contents in the left ventricular tissue and plasma were measured by nitrate reduction method to represent nitric oxide (NO)contents.Expression levels of CST in the left ventricle, kidney, medulla oblongata and adrenal gland,as well as eNOS and iNOS, were tested by Western blot. Results:①The 2K1C group had higher tail-artery blood pressure(P<0.01) and were more marked presence of right ventricular hypertrophy than those of sham group (P<0.01). Compared with Sham group, plasma CST content in 2K1C group was decreased by 226% (P<0.01), while plasma NE content in 2K1C group was increased by 246% (P<0.01), expression levels of chromograminA(Chga) in medulla oblongata of 2K1C group were increased by 108%, in leftventricle and kidneywere decreased by 60% and 30%, respectively (P<0.05).the content of NO in left ventricular and plasmawere increased by 46% and 24% respectively. ②The carotid arterial blood pressure of 2K1C group markedly reduced after administration of CST.③Compared with 2K1C group, the content of NO in left ventricul and plasma of 2K1C+CST group were increased by 35% and 19% respectively(P<0.05). The expression of eNOS in left ventricular of 2K1C+CST group were also obviously increased. Conclusion:The CST expression of 2K1C-induced renal hypertension rats is reduced and the effects of exogenous CST lowering their blood pressure may be related to NO/NOS system.Therefore, we speculate CST could contribute to the pathogenesis and progression of renal hypertension.

Key words: hypertension, renal, catestatin, nitric oxide, norepinephrine

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