Effect of Renal Sympathetic Denervation on Renin Activity and Ventricular Remodeling in Spontaneously Hypertensive Rats in Acute Stage
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摘要:
目的 观察自发性高血压大鼠去肾动脉交感神经术后无创血压、血浆及组织肾素活性和心脏组织结构的变化，旨在评价去肾动脉交感神经治疗对高血压相关心脏重塑的影响。 方法 本研究纳入雄性12周龄自发性高血压大鼠（SHR）50只，平均体重（265±12） g。随机分为手术处理组（M组）和空白对照组（B组），据处理范围及方式不同，再随机将M组大鼠不同亚组（左侧组，右侧组，双侧组，假手术组），5只WKY大鼠为阴性对照组（F组）。测定各组大鼠基础血压值、体重及血浆肾素活性。对M组大鼠制作去肾动脉交感神经模型。观察围术期无创血压及血浆肾素活性变化，并行心脏组织行病理组织学观察及心脏、肾脏组织肾素活性检测。 结果 去肾动脉神经术不同处理组间心脏病理组织学检测指标变化可见显著差异，包括HW/BW值、心肌厚度及心肌肥大，间质局部水肿，纤维组织增生等；手术组血浆RAAS相关因子经去肾动脉神经处理后均出现显著下降趋势，[（PRA（244.40±11.5） vs （228.23±7.5），P < 0.05]；AngⅡ[（4.10±0.35） vs （3.41±0.28），P < 0.05]；ALD[（133.44±6.98） vs （119.85±4.12），P < 0.05]；心肌AngII、AngI、ALD、ACE含量与血压、HW/BW及心肌厚度之间相关性有显著意义；免疫组化定量组间对比分析提示手术处理组大鼠肾脏组织AngⅠ，AngⅡ及NA IOD值显著低于空白对照及假手术组, 差异有统计学意义（P < 0.05）。 结论 去肾动脉交感神经术可有效降低循环及组织水平RAAS相关因子水平，改善高血压大鼠心室重塑。 Abstract:Objectives To observe the effect of renal sympathetic denervation on acute ventricular remodeling in SHR. Methods This experiment enrolled 50 male rats of SHR, the average weight was （265±12） g. According to the difference of intervention way, they were randomly divided into operation intervention group（M） and blank control group（B）. The group M were divided into groups of Left, Right, Dual and Sham-operation randomly again. Five rats of WKY were enrolled as negative control group. The blood pressure, weight and the activity of plasma renin were measured for all rats. The mode of Renal Sympathetic Denervation was made by operation. After operation, they were executed and and their hearts and kidney tissues were collected. The index of weight of body and heart, HW/BW, thickness of ventricular tissue and its histopathology were collected and analyzed, while, the level of RAAS factors were dectected in circulation and tissue. Results There were statistically significant differences among group B and S with group M（P < 0.05）, including HW/BW, cardiac muscle cell hypertrophy, interstitial edema and fibrosis under the microscope. The concentration of factors, including AngⅠ, AngⅡ, ALD and NA, were down regulated in circulation and tissue, and there were statistically significant differences between operation with control group respectively. Conclusions Renal sympathetic denervation has significant alleviation effect on acute ventricular remodeling in SHR. These effect maybe come from decreasing the level of factor related with RAAS. -
图 1 图1.SHR大鼠围术期收缩压（SBP）及舒张压（DBP）的变化趋势
D0组：空白对照组，S组：假手术组，DL左侧处理组，DR组：右侧处理组，DB组：双侧处理组。
Figure 1. Variation trend of systolic blood pressure and diastolic pressure in peri-operative period
图 2 不同处理组围术期血浆PRA，AngⅡ及ALD浓度变化比较
Figure 2. Comparison of change concentration in blood plasm PRA，AngⅡand Ald among different groups
图 3 各组间大鼠心肌厚度及HW/BW值比较
Figure 3. Comparison of ventricular muscle thickness and HW/BW among different groups
图 4 各组间大鼠心肌厚度及HW/BW值比较
Figure 4. Comparison of ventricular muscle thickness and HW/BW among different groups
图 5 不同处理组大鼠肾脏组织因子免疫组化定性分析。
WKY组：阴性对照组，D0组：空白对照组，S组：假手术组，D组：手术处理组。
Figure 5. Qualitative analysis of the factor in pathological sections of kidney tissue by Immunohistochemistry
图 6 不同组肾动脉周围剥离组织病理切片观察
A：未做去肾动脉神经处理的肾动脉周围可见神经组织分布；B：做了去肾动脉神经处理的肾动脉周围未见明显见神经组织分布。
Figure 6. Comparison of the pathological sections of tissue around renal artery by HE stain in different groups
图 7 不同组大鼠心肌病理切片HE染色观察
A：左侧处理组大鼠心肌HE染色；B：右侧处理组大鼠心肌HE染色；C：双侧处理组大鼠心肌HE染色；D：假手术组大鼠心肌HE染色。
Figure 7. Comparison of the pathological sections of ventricular tissue by HE stain in different groups
图 8 不同组大鼠心肌病理切片masson染色观察分析
A：左侧处理组大鼠心肌；B：右侧处理组大鼠心肌；C：双侧处理组大鼠心肌；D：假手术组大鼠心肌。
Figure 8. Comparison of the pathological sections of ventricular tissue by Masson stain in different groups
表 1 基础各实验组大鼠体重、心率比较（
${{\bar x}} \pm {{s}}$ ）Table 1. Baseline parameters of differential rat groups（
$\bar x\pm s $ ）组别 n 体重（g） 心率（次/min） 阴性对照组 5 282.40 ± 9.84 422.40 ± 39.70 空白对照组组 10 284.90 ± 15.91 424.30 ± 56.98 假手术组组 10 282.90 ± 15.57 421.60 ± 79.95 手术处理组 30 281.20 ± 15.40 423.43 ± 36.15 
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表 3 各组间大鼠心肌厚度及HW/BW值比较（
${{\bar x}} \pm {{s}}$ ）Table 3. Comparison of ventricular muscle thickness and HW/BW among different groups （
$\bar x \pm s $ ）组别 n 心肌厚度（mm） HW/BW（mg/g） 未去神经处理组 20 5.12 ± 0.35 12.58 ± 0.37 去神经处理组 23 4.03 ± 0.37 12.06 ± 0.52
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表 2 各组间大鼠心肌厚度及HW/BW值比较（
${{\bar x}} \pm {{s}}$ ）Table 2. Comparison of ventricular muscle thickness and HW/BW among different groups （
$\bar x \pm s $ ）组别 n 心肌厚度（mm） HW/BW（mg/g） 左侧处理组 8 4.11 ± 0.34 12.34 ± 0.29 右侧处理组 8 4.24 ± 0.39 12.31 ± 0.28 双侧处理组 7 3.70 ± 0.13 11.46 ± 0.46 假手术组 10 5.15 ± 0.26 12.57 ± 0.25 空白对照组 10 5.10 ± 0.21 12.59 ± 0.49 阴性对照组组 5 2.98 ± 0.16 11.38 ± 0.37
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表 4 各组间大鼠心肌组织ACE、AngI、AngII、ALD的比较（
$\bar x\pm s $ ）Table 4. Comparison of AngII，AngI，ALD，ACE among different group （
$ \bar x\pm s$ ）组别 n AngII AngI ALD ACE 左侧处理组 8 1.42 ± 0.05 1.42 ± 0.08 1.41 ± 0.09 1.41 ± 0.08 右侧处理组 8 1.49 ± 0.11 1.40 ± 0.77 1.41 ± 0.76b 1.39 ± 0.89 双侧处理组 7 1.18 ± 0.04 1.17 ± 0.04 1.13 ± 0.05 1.13 ± 0.05 假手术组 10 1.96 ± 0.15 1.95 ± 0.15 1.92 ± 0.14f 1.90 ± 0.11 空白对照组 10 2.00 ± 0.18 1.96 ± 0.17 1.95 ± 0.17 1.93 ± 0.15 阴性对照组 5 0.65 ± 0.08 0.56 ± 0.11 0.58 ± 0.11g 0.49 ± 0.08 总处理组 23 1.37 ± 0.15 1.34 ± 0.13 1.32 ± 0.15 1.31 ± 0.15
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表 5 大鼠心肌RAAS相关因子含量与血压、HW/BW及心肌厚度之间相关性分析
Table 5. Correlation analysis among AngII，AngI，ALD，ACE with blood pressure，HW/BW and ventricular muscle thickness
项目 AngI AngII ALD ACE r P r P r P r P 收缩压 0.674 0.001 0.667 0.001 0.707 0.001 0.722 0.001 舒张压 0.744 0.001 0.722 0.002 0.747 0.001 0.780 0.001 HW/BW 0.701 0.002 0.752 0.001 0.708 0.001 0.741 0.001 心肌厚度 0.914 0.001 0.908 0.001 0.912 0.001 0.906 0.001
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表 6 不同处理组大鼠肾脏组织因子免疫组化IOD值对比分析（
${{\bar x}} \pm {{s}}$ ）Table 6. Comparison analysis IOD of tissue factor in kidney by immunohistochemistry （
${{\bar x}} \pm {{s}}$ ）组别 AngⅠ AngⅡ NA 阴性对照组WKY（n = 5） 0.11 ± 0.01 0.12 ± 0.00 0.06 ± 0.01 空白对照组D0（n = 10） 0.29 ± 0.02 0.36 ± 0.02 0.16 ± 0.01 假手术组S（n = 10） 0.28 ± 0.01 0.35 ± 0.01 0.17 ± 0.14 手术处理组D（n = 23） 0.18 ± 0.01 0.30 ± 0.01 0.13 ± 0.01
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