肾去神经术抗自发性高血压大鼠心肌胶原纤维增生的研究

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目的通过研究肾去神经术(RDN)对自发性高血压大鼠(SHR)心肌组织血管紧张素Ⅱ(AngⅡ)表达的影响,验证RDN对SHR大鼠血压调节作用,探讨其抗心肌胶原纤维增生的作用及其可能机制。方法 30只约12周龄雄性SHR大鼠随机分成3组,分别为:手术组、假手术组、无手术对照组(阳性对照组),另取10只相同体重雄性WKY大鼠作为正常血压大鼠(阴性对照组)。术后10周处死实验动物,取心肌、肾脏组织,测定左心室质量分数(LVMI),酶联免疫吸附法(ELISA)测定肾脏匀浆组织去甲肾上腺素(NE)浓度及心肌匀浆组织AngⅡ浓度,病理切片HE染色观察心肌细胞形态,苦味酸天狼星红染色计算心肌胶原纤维含量。结果术后第2、4、6、8周收缩压及舒张压手术组均明显低于假手术组、无手术对照组(P<0.05),LVMI手术组[(2.48±0.12)mg/g]明显低于假手术组[(2.91±0.26)mg/g]、无手术对照组[(2.82±0.32)mg/g](P<0.05),肾脏NE含量及心肌匀浆液中AngⅡ含量手术组[NE:(80.26±7.42)ng/g;AngⅡ:(375.50±23.05)pg/g]明显低于假手术组[NE:(170.02±11.75)ng/g;AngⅡ:(421.52±36.84)pg/g]、无手术对照组[NE:(183.30±18.23)ng/g;AngⅡ:(419.07±43.87)pg/g](P<0.05),心肌胶原纤维手术组[1 631(888~3 121)]含量明显低于假手术组[5 961(3 539~13 456)]、无手术对照组[6 024(3 417~12 022)](P<0.05)。结论 RDN能明显降低SHR大鼠血压,抑制其心肌胶原纤维增生和左心室质量增加,此机制可能与抑制肾交感神经及降低心肌AngⅡ表达有关。 Objective To investigate the effect of renal denervation (RDN) on the expression of angiotensin Ⅱ (AngⅡ) in spontaneously hypertensive rats (SHR) and to verify the effect of RDN on blood pressure regulation in SHR rats The role and possible mechanism. Methods Thirty male SHR rats, aged about 12 weeks, were randomly divided into three groups: operation group, sham operation group and non-operation control group (positive control group). Another 10 male WKY rats of the same weight were used as normal blood pressure Mouse (negative control group). The experimental animals were sacrificed 10 weeks after the operation. The myocardium and kidney tissue were taken for measurement of left ventricular mass fraction (LVMI), and the concentration of norepinephrine (NE) in renal homogenate tissue and the level of AngⅡ in myocardium homogenate were determined by enzyme-linked immunosorbent assay (ELISA) The cardiomyocyte morphology was observed by HE staining and the collagen content of myocardium was calculated by picric acid Sirius red staining. Results The systolic blood pressure and diastolic blood pressure were significantly lower in the operation group than those in the sham operation group and the control group (P <0.05) at the 2nd, 4th, 6th and 8th week after operation, and were (2.48 ± 0.12) mg / g in the LVMI group (2.91 ± 0.26) mg / g in sham-operation group, (2.82 ± 0.32) mg / g in non-operation control group, P <0.05) NE: (80.26 ± 7.42) ng / g; AngⅡ: (375.50 ± 23.05) pg / g] were significantly lower than those in the sham operation group [NE: (170.02 ± 11.75) ng / g; AngⅡ: (421.52 ± 36.84) pg / g (183.30 ± 18.23) ng / g; Ang Ⅱ: (419.07 ± 43.87) pg / g] (P <0.05) The content was significantly lower than that of the sham operation group [5 961 (5339 ~ 13 456)] and no operation control group [6 024 (3417-12 022)] (P <0.05). Conclusion RDN can significantly reduce the blood pressure of SHR rats and inhibit the increase of myocardial collagen fibers and the left ventricular mass. This mechanism may be related to the inhibition of renal sympathetic nerve and the decrease of myocardial Ang Ⅱ expression.
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