Please wait a minute...
浙江大学学报（医学版）
浙江大学学报（医学版）  2013, Vol. 42 Issue (5): 550-555    DOI: 10.3785/j.issn.1008-9292.2013.05.012
论著     
去肾交感神经术对高血压大鼠左室肥厚及其炎症因子的影响
谭丽华1，2，李小刚1，郭运忠1，唐晓鸿1，杨侃1，蒋卫红1
1.中南大学湘雅三医院心内科，湖南 长沙 410013；
2.湖南省马王堆疗养院心内科，湖南 长沙 410016；
Effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats
TAN Li-Hua1，2, LI Xiao-Gang1, GUO Yun-Zhong1, TANG Xiao-Hong1, YANG Kan1, JIANG Wei-Hong1
1.Department of Cardiology，the Third Xiangya Hospital of Central-South University，Changsha 410013，China; 2.Department of Cardiology，Hunan Provincial Mawangdui Sanatorium，Changsha 410016，China；
 全文: PDF(1315 KB)   HTML ( ) 
摘要：

目的：观察去肾交感神经术对自发性高血压（SHR）大鼠血压、左室肥厚及心肌局部Toll样受体4（TLR4)/核转录因子(NF)-κB炎症通路表达的影响，探讨去肾交感神经术抗心肌重塑作用的可能机制。
方法：对SHR大鼠进行肾交感神经切除或假手术处理，并以12周龄的SHR和WKY大鼠做对照。术后1、6周分批处死大鼠，留取心脏组织，称量左室心肌质量并计算左室质量指数（LVMI）；免疫组化法观察左室心肌组织TLR4、肿瘤坏死因子（TNF）-α及白介素（IL）-6的变化；Western blot法检测心肌TLR4、NF-κB、TNF-α、IL-6蛋白表达水平。
结果：SHR大鼠的血压、LVMI及心肌组织TLR4、NF-κB、TNF-α、IL-6 蛋白表达较WKY大鼠显著升高（P<0.05)。肾交感神经切除1周后，SHR大鼠的血压、LVMI及心肌组织TLR4、NF-κB、TNF-α、IL-6蛋白表达较对照组及假手术组大鼠明显减少（P<0.05)；6周后，SHR大鼠的血压与对照组及假手术组大鼠差异无统计学意义（P>0.05），但LVMI及TLR4、NF-κB、TNF-α、IL-6较假手术组大鼠降低（P<0.05)。
结论：去肾交感神经术能够显著延缓自发性高血压大鼠左室肥厚的进展，其作用机制除与压力负荷的减轻有关外，可能还与心肌局部免疫炎症反应的减弱有关。
关键词： 大鼠,近交SHR;  高血压;  交感神经切除术;  肾;  心肌;  核因子κB;  肿瘤坏死因子α;  Toll样受体4;  心室功能,左    
Abstract:

Objective： To investigate the effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats.
Methods： Thirty six spontaneously hypertensive rats (SHR) were divided into 3 groups with 12 animals in each group: SHR control group，operation group and sham operation group.Bilateral renal sympathectomy or sham operation were performed in operation and sham groups，respectively; another 12 WKY rats served as normal controls.The blood pressure and body weight were examined weekly.The animals were sacrificed at w1 and w6，rat hearts were collected and left ventricular mass index (LVMI) was calculated.The expression of TLR4，TNF-α and IL-6 in heart tissue were detected by immunohistochemistry and Western blot.
Results： The systolic blood pressure \[(201.67±11.09)mmHg vs (140.0±10.86)mmHg，P<0.05\]，diastolic blood pressure \[(144.50±10.48)mmHg vs (78.50±7.32)mmHg，P<0.05\]，LVMI (2.44±0.05 vs 1.93±0.05，P<0.05)，the expression of TLR4 (0.298±0.004 vs 0.126±0.004，P<0.05)，NF-κB (0.249±0.006 vs 0.195±0.005, P<0.05)，TNF-α (0.323±0.004 vs 0.146±0.004，P <0.05)，IL-6 (0.283±0.005 vs 0.207±0.006，P<0.05) in SHR control group were significantly higher than those in WKY group.Compared to sham operation group，the systolic blood pressure (157.30±9.35 vs 197.30±11.5，P<0.05)， diastolic blood pressure (112.50±6.25 vs 146.80±7.6,P<0.05)，LVMI (2.32±0.04 vs 2.57±0.09, P<0.05，TLR4 (0.198±0.006 vs 0.317±0.008，P<0.05)，NF-κB (0.208±0.006 vs 0.332±0.007,P<0.05)，TNF-α (0.27±0.009 vs 0.375±0.004，P<0.05)，IL-6 (0.218±0.004 vs 0.376±0.009,P<0.05) in operation group were all decreased at w1 after sympathectomy.Six weeks after the operation，there were no significant differences in systolic blood pressure (197.50±12.13 vs 208.83±10.23，P>0.05) and diastolic blood pressure (150.33±7.74 vs 151.50±8.22,P>0.05) between denervated and sham-operated SHRs; however，the LVMI (2.46±0.07 vs 2.81±0.05，P<0.05) and the expression of TLR4(0.301±0.009 vs 0.567±0.006, P<0.05)，NF-κB (0.251±0.004 vs 0.476±0.009，P<0.05)，TNF-α (0.324±0.005 vs 0.535±0.006,P<0.05，IL-6 (0.285±0.009 vs 0.549±0.007,P<0.05) in operation group were still significantly lower than those in sham operation group.
Conclusion： Renal sympathetic denervation can significantly delay the progression of LVH in SHR，which may associated with lowering blood pressure and decreasing expression of TLR4，NF-κB，TNF-α，IL-6 in myocardial tissue.
Key words: Rats, Inbred SHR    Hypertension    Sympathectomy    Kidney    Myocardium    NF-kappa B    Tumor necrosis factor-alpha    Toll-like receptor 4    Ventricular function, Left
收稿日期: 2012-07-19 出版日期: 2013-09-25
CLC:  R 742.1  
基金资助:

湖南省科学技术厅科技计划（2011FJ4269）.
通讯作者: 蒋卫红（1968-），女，博士，副教授，硕士生导师，从事老年心血管病研究；E-mail:jwhxy3@126.com   
作者简介: 谭丽华（1985-），女，硕士，从事老年心血管病研究；E-mail:13461031@qq.com
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
谭丽华
李小刚
郭运忠
唐晓鸿
杨侃
蒋卫红

引用本文:

谭丽华, 李小刚, 郭运忠, 唐晓鸿, 杨侃, 蒋卫红. 去肾交感神经术对高血压大鼠左室肥厚及其炎症因子的影响[J]. 浙江大学学报（医学版）, 2013, 42(5): 550-555.

TAN Li-Hua, LI Xiao-Gang, GUO Yun-Zhong, TANG Xiao-Hong, YANG Kan, JIANG Wei-Hong. Effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats. Journal of ZheJiang University(Medical Science), 2013, 42(5): 550-555.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2013.05.012    或    http://www.zjujournals.com/med/CN/Y2013/V42/I5/550

[1] DORN G W II.The fuzzy logic of physiological cardiac hypertrophy
[J] Hypertension，2007，49(5):962-970.
[2] SALLES G F，FISZMAN R，CARDOSO C R，et al.Relation of left ventricular hypertrophy with systemic inflammation and endothelial damage in resistant hypertension
[J] Hypertension，2007，50(4):723-728.
[3] BOMBELLI M，FACCHETTI R，CARUGO S，et al.Left ventricular hypertrophy increases cardiovascular risk independently of in-office and out-ofoffice blood pressure values
[J] J Hypertens，2009，27(12):2458-2464.
[4] DIBONA G F.Neural control of the kidney:past，present，and future
[J] Hypertension，2003，41(3 Pt 2):621- 624．
[5] DIBONA G F.Physiology in perspective:The Wisdom of the body.Neural control of the kidney
[J] Am J Physiol Regul Integr Comp Physiol，2005，289(3):R633-R641.
[6] KRUM H，SCHLAICH M，WHITBOURN R，et al.Catheter-based renal sympathetic denervation for resistant hypertension a multicentre safety and proof-of-principle cohort study
[J] Lancet，2009， 373( 9671):1275-1281.
[7] WEINSTOCK M，GORODETSKY E，KALMAN R.Renal denervation prevents sodium retention and hypertension in salt-sensitive rabbits with genetic baroreflex impairment
[J] Clin Sci(Lond)，1996，90(4):287-293.
[8] KIMURA G，FUKUTA H.Catheter-based renal sympathetic denervation for treatment of hypertension
[J] Nippon Naika Gakkai Zasshi，2011，100(2):441-445.
[9] MAHFOUD F，SCHLAICH M，KINDERMANN I，et al.Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension:a pilot study
[J] Circulation，2011，123(18):1940-1946.
[10] PROCHNAU D，LAUTEN A，BUSCH M，et al.Catheter-based radiofrequency ablation therapy of the renal sympathetic-nerve system for drug resistant hypertension in a patient with end-stage renal disease
[J] Int J Cardiol，2011，5(12):234-239.
[11] KUWAHARA F，KAI H，TOKUDA K，et al.Hypertensive myocardial fibrosis and diastolic dysfunction.Another model of inflammation?
[J] Hypertension，2004，43(4):739-745.
[12] TSIOUFIS C，STOUGIANNOS P，KAKKAVAS A，et al.Relation of left ventricular concentric remodeling to levels of C-reactive protein and serum amyloid A in patients with essential hypertension
[J] Am J Cardiol，2005，96(2):252-256.
[13] FRANTZ S，KOBZIK L，KIM Y D，et al.Toll 4(TLR4) expression in cardiac myocytes in normal and failing myocardium
[J] J Clin Invest，1999，104(3):271-280.
[14] ZHANG D，GAUSSIN V，TAFFET G E，et al.TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice
[J] Nat Med，2000，6(5):556-563.
[15] PURCELL N H，MOLKENTIN J D.Is nuclear factor-κB an attractive therapeutic target for treating cardiac hypertrophy
[J] Circulation，2003，108(6):638-640.
[16] CHROUSOS G P.The stress response and immune function:Clinical implications
[J] Ann NY Acad Sci，2000，917:38-47.
[17] LEVICK S P，MURRAY D B，JANICKI J S，et al.Sympathetic nervous system modulation of inflammation and remodeling in the hypertensive heart
[1] 沈杰,陈闻东,姬开达,高平进,朱鼎良. Arg188Gln(G/A)突变对犬尿氨酸酶活性的影响[J]. 浙江大学学报（医学版）, 2017, 46(6): 643-648.
[2] 李瑶,陈慧. 胰岛素瘤合并继发性肾上腺皮质功能不全一例[J]. 浙江大学学报（医学版）, 2017, 46(6): 662-665.
[3] 马婷婷,王毅,陈晓倩,赵筱萍. 液相色谱-质谱联用导向的黄葵胶囊肾保护活性物质研究[J]. 浙江大学学报（医学版）, 2017, 46(1): 66-73.
[4] 叶彬娴 等. 慢性肾脏病患者主动脉僵硬度相关指数变化及影响因素分析[J]. 浙江大学学报（医学版）, 2016, 45(5): 508-514.
[5] 严凌 等. 阿托伐他汀可改善急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗后无复流现象[J]. 浙江大学学报（医学版）, 2016, 45(5): 530-535.
[6] 蒋倩倩 等. 高血压伴阻塞性睡眠呼吸暂停低通气综合征患者肾功能影响因素分析[J]. 浙江大学学报（医学版）, 2016, 45(3): 261-267.
[7] 姜丽娇 等. 非全身型幼年特发性关节炎患儿外周血T辅助细胞1/2细胞因子水平分析[J]. 浙江大学学报（医学版）, 2016, 45(3): 281-286.
[8] 王炬峰 等. 高效抗逆转录病毒治疗对人类免疫缺陷病毒感染者骨代谢的影响[J]. 浙江大学学报（医学版）, 2016, 45(3): 228-235.
[9] 郎夏冰 等. 中国住院患者急性肾损伤流行病学调查现状[J]. 浙江大学学报（医学版）, 2016, 45(2): 208-213.
[10] 柳珊珊 等. 足细胞功能紊乱与微小病变性肾病[J]. 浙江大学学报（医学版）, 2016, 45(2): 214-218.
[11] 陈思腾 等. 肾移植受者与普通患者泌尿系统感染的比较[J]. 浙江大学学报（医学版）, 2016, 45(2): 201-207.
[12] 边薇 等. 临时血液透析对维持性腹膜透析患者生存预后的影响[J]. 浙江大学学报（医学版）, 2016, 45(2): 195-200.
[13] 来翀 等. 转移性肾细胞癌靶向治疗的分子生物学基础[J]. 浙江大学学报（医学版）, 2016, 45(1): 91-97.
[14] 赵雅莹 等. 门静脉高压自发性分流患者食管胃底静脉曲张特点[J]. 浙江大学学报（医学版）, 2016, 45(1): 75-80.
[15] 葛亚力, 史宏伟, 朱雯霏, 马正良, 魏海燕, 顾小萍, 鲍红光. 乌司他丁对冠状动脉搭桥术后患者认知功能障碍的影响[J]. 浙江大学学报（医学版）, 2015, 44(5): 532-538.