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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; |
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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.
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Received: 19 July 2012
Published: 25 September 2013
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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
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
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