猪肾动脉射频消融去神经术对内皮素1及其受体的影响
|
摘要
目的探讨射频消融肾去神经(renal denervation, RDN)术对高脂饮食(high-fat diet, HFD)猪的内皮素1(endothelin-1, ET-1)及其受体的影响。方法健康雄性巴马小型猪15头,随机分为对照组、HFD组和HFD+RDN组各5头,对照组给予正常饮食,HFD组给予HFD,HFD+RDN组行双侧肾动脉射频消融RDN术,并给予HFD。6个月后,检测3组血清总胆固醇(total cholesterol, TC)、三酰甘油(triacylglycerol, TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)和血肌酐(serum creatinine, SCr)水平。采用ELISA法检测实验前、6个月后血浆及6个月后肾组织和肺组织肾素、血管紧张素Ⅱ(angiotensinⅡ, AngⅡ)、醛固酮(aldosterone, Ald)和ET-1水平,采用Western blot法检测6个月后肾组织与肺组织ET-1、内皮素A受体(endothelin A receptor, ET_AR)、内皮素B受体(endothelin B receptor, ET_BR)、内皮素转化酶1(endothelin converting enzyme 1, ECE1)蛋白相对表达量。结果 6个月后,HFD组体质量和血清TC水平高于对照组(P<0.05),血清HDL-C水平低于对照组(P<0.05),HFD组体质量、血清TC和HDL-C水平与HFD+RDN组比较差异均无统计学意义(P>0.05),3组血清TG、LDL-C和SCr水平比较差异均无统计学意义(P>0.05);HFD组血浆和肾组织AngⅡ[(202.11±33.76)、(13.43±2.22)ng/L]和ET-1水平[(1.88±0.14)、(17.87±2.36)ng/L]均高于对照组[(128.43±12.45)、(8.72±2.17)ng/L,(1.51±0.08)、(12.80±2.93)ng/L]和HFD+RDN组[(160.95±19.50)、(10.71±1.17)ng/L,(1.66±0.11)、(14.62±0.94)ng/L](P<0.05),3组血浆和肾组织肾素和Ald水平比较差异均无统计学意义(P>0.05);HFD组肺组织ET-1水平[(0.54±0.09)ng/L]高于对照组[(0.39±0.09)ng/L]和HFD+RDN组[(0.41±0.06)ng/L](P<0.05),3组肺组织肾素、AngⅡ和Ald水平比较差异均无统计学意义(P>0.05);HFD组肾组织和肺组织ECE1(0.54±0.11、0.63±0.12)、ET-1(0.59±0.10、0.58±0.06)和ET_AR蛋白相对表达量(0.59±0.10、0.36±0.10)均高于对照组[ECE1(0.28±0.08、0.28±0.06)、ET-1(0.13±0.02、0.29±0.08)、ET_AR (0.39±0.06、0.14±0.05)]和HFD+RDN组[ECE1(0.42±0.07、0.49±0.06)、ET-1(0.28±0.17、0.46±0.05)、ET_AR(0.48±0.03、0.17±0.06)](P<0.05),HFD组肾组织ET_BR蛋白相对表达量(0.18±0.03)低于对照组(0.62±0.07)和HFD+RDN组(0.38±0.10)(P<0.05),3组肺组织ET_BR蛋白相对表达量比较差异无统计学意义(P>0.05)。结论 RDN术可抑制HFD诱导猪的血浆、肾和肺组织中ET-1及其受体表达水平改变。
Objective To investigate the influence of radiofrequency ablation renal denervation(RDN) on endothelin-1(ET-1) and its receptors in high-fat diet(HFD) pigs. Methods Fifteen healthy male Bama miniature pigs were randomly divided into control group, HFD group and HFD+RDN group, with 5 pigs in each group. Control group was given normal diet, HFD group was given HFD, and HFD+RDN group underwent bilateral renal artery radiofrequency ablation RDN and was given HFD. After 6 months, the serum levels of total cholesterol(TC), triacylglycerol(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C) and creatinine(SCr) were detected in 3 groups. The levels of renin, angiotensin Ⅱ(Ang Ⅱ), aldosterone(Ald) and ET-1 in plasma before experiment and after 6 months and in renal and lung tissue after 6 months were detected by ELISA.The relative expressions of ET-1,endothelin A receptor(ET_AR),endothelin B receptor(ET_BR)and endothelin converting enzyme 1(ECE1)protein in renal and lung tissue after 6 months were detected by Western blot.Results After 6 months,the body mass and TC level were significantly higher,and HDL-C level was significantly lower in HFD group than that in control group(P<0.05).There were no significant differences in body mass,TC level and HDL-C level between HFD group and HFD+RDN group(P>0.05).There were no significant differences in the levels of TG,LDL-C and SCr among three groups(P>0.05).The levels of AngⅡ((202.11±33.76),(13.43±2.22)ng/L)and ET-1((1.88±0.14),(17.87±2.36)ng/L)in plasma and renal tissue were significantly higher in HFD group than those in control group((128.43±12.45),(8.72±2.17)ng/L;(1.51±0.08),(12.80±2.93)ng/L)and HFD+RDN group((160.95±19.50),(10.71±1.17)ng/L;(1.66±0.11),(14.62±0.94)ng/L)(P<0.05),and there were no significant differences in the levels of renin and Ald in plasma and renal tissue among three groups(P>0.05).The level of ET-1 in lung tissue was significantly higher in HFD group((0.54±0.09)ng/L)than that in control group((0.39±0.09)ng/L)and HFD + RDN group((0.41±0.06)ng/L)(P<0.05).There were no significant differences in the levels of renin,AngⅡ and Ald among three groups(P>0.05).The relative expressions of ECE1(0.54±0.11,0.63±0.12),ET-1(0.59±0.10,0.58±0.06)and ET_AR protein(0.59±0.10,0.36±0.10)in renal tissue and lung tissue in HFD group were significantly higher than those in control group(0.28±0.08,0.28±0.06;0.13±0.02,0.29±0.08;0.39±0.06,0.14±0.05)and HFD+RDN group(0.42±0.07,0.49±0.06;0.28±0.17,0.46±0.05;0.48±0.03,0.17±0.06)(P<0.05).The relative expression of ET_BR protein in renal tissue was significantly lower in HFD group(0.18±0.03)than that in control group(0.62±0.07)and HFD+RDN group(0.38±0.10)(P<0.05),and showed no significant difference in lung tissue among three groups(P>0.05).Conclusion RDN can inhibit the expressions of ET-1 and its receptors in plasma,renal tissue and lung tissue of pigs induced by HFD.
Objective To investigate the influence of radiofrequency ablation renal denervation(RDN) on endothelin-1(ET-1) and its receptors in high-fat diet(HFD) pigs. Methods Fifteen healthy male Bama miniature pigs were randomly divided into control group, HFD group and HFD+RDN group, with 5 pigs in each group. Control group was given normal diet, HFD group was given HFD, and HFD+RDN group underwent bilateral renal artery radiofrequency ablation RDN and was given HFD. After 6 months, the serum levels of total cholesterol(TC), triacylglycerol(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C) and creatinine(SCr) were detected in 3 groups. The levels of renin, angiotensin Ⅱ(Ang Ⅱ), aldosterone(Ald) and ET-1 in plasma before experiment and after 6 months and in renal and lung tissue after 6 months were detected by ELISA.The relative expressions of ET-1,endothelin A receptor(ET_AR),endothelin B receptor(ET_BR)and endothelin converting enzyme 1(ECE1)protein in renal and lung tissue after 6 months were detected by Western blot.Results After 6 months,the body mass and TC level were significantly higher,and HDL-C level was significantly lower in HFD group than that in control group(P<0.05).There were no significant differences in body mass,TC level and HDL-C level between HFD group and HFD+RDN group(P>0.05).There were no significant differences in the levels of TG,LDL-C and SCr among three groups(P>0.05).The levels of AngⅡ((202.11±33.76),(13.43±2.22)ng/L)and ET-1((1.88±0.14),(17.87±2.36)ng/L)in plasma and renal tissue were significantly higher in HFD group than those in control group((128.43±12.45),(8.72±2.17)ng/L;(1.51±0.08),(12.80±2.93)ng/L)and HFD+RDN group((160.95±19.50),(10.71±1.17)ng/L;(1.66±0.11),(14.62±0.94)ng/L)(P<0.05),and there were no significant differences in the levels of renin and Ald in plasma and renal tissue among three groups(P>0.05).The level of ET-1 in lung tissue was significantly higher in HFD group((0.54±0.09)ng/L)than that in control group((0.39±0.09)ng/L)and HFD + RDN group((0.41±0.06)ng/L)(P<0.05).There were no significant differences in the levels of renin,AngⅡ and Ald among three groups(P>0.05).The relative expressions of ECE1(0.54±0.11,0.63±0.12),ET-1(0.59±0.10,0.58±0.06)and ET_AR protein(0.59±0.10,0.36±0.10)in renal tissue and lung tissue in HFD group were significantly higher than those in control group(0.28±0.08,0.28±0.06;0.13±0.02,0.29±0.08;0.39±0.06,0.14±0.05)and HFD+RDN group(0.42±0.07,0.49±0.06;0.28±0.17,0.46±0.05;0.48±0.03,0.17±0.06)(P<0.05).The relative expression of ET_BR protein in renal tissue was significantly lower in HFD group(0.18±0.03)than that in control group(0.62±0.07)and HFD+RDN group(0.38±0.10)(P<0.05),and showed no significant difference in lung tissue among three groups(P>0.05).Conclusion RDN can inhibit the expressions of ET-1 and its receptors in plasma,renal tissue and lung tissue of pigs induced by HFD.
引文
[1] 赵林蔚,朱利杰,优张,等.肾动脉射频消融去交感神经术研究进展[J].中华实用诊断与治疗杂志,2017,31(2):194-196.
[2] 苏恩勇,高传玉.内皮功能障碍与心血管疾病关系的研究进展[J].中华实用诊断与治疗杂志,2018,32(6):622-624.
[3] KRUM H, SCHLAICH M P, SOBOTKA P A, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study[J]. Lancet,2014,383(9917):622-629.
[4] BRUNO R M, SUDANO I, GHIADONI L, et al. Interactions between sympathetic nervous system and endogenous endothelin in patients with essential hypertension[J]. Hypertension,2011,57(1):79-84.
[5] LI M W, MIAN M O, BARHOUMI T, et al. Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice[J]. Arterioscler Thromb Vasc Biol,2013,33(10):2306-2315.
[6] BRIONES A M, ARAS-LOPEZ R, ALONSO M J, et al. Small artery remodeling in obesity and insulin resistance[J]. Curr Vasc Pharmacol,2014,12(3):427-437.
[7] 杨晓航,赵林蔚,苏恩勇,等.肾动脉内膜射频消融术对小型猪肾动脉内膜的影响[J].中华实用诊断与治疗杂志,2018,32(5):422-425.
[8] ZHENG L H, SUN W, YAO Y, et al. Associations of big endothelin-1 and C-reactive protein in atrial fibrillation[J]. J Geriatr Cardiol,2016,13(5):465-470.
[9] LU J, LING Z, CHEN W, et al. Effects of renal sympathetic denervation using saline-irrigated radiofrequency ablation catheter on the activity of the renin-angiotensin system and endothelin-1[J]. J Renin Angiotensin Aldosterone Syst,2014,15(4):532-539.
[10] CHEN D D, DONG Y G, YUAN H, et al. Endothelin-1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension[J]. Hypertension,2012,59(5):1037-1043.
[11] MORRIS R, SPENCER S K, KYLE P B, et al. Hypertension in an animal model of HELLP syndrome is associated with activation of endothelin-1[J]. Reprod Sci,2016,23(1):42-50.
[12] LEKONTSEVA O, CHAKRABARTI S, DAVIDGE S T. Endothelin in the female vasculature: a role in aging?[J]. Am J Physiol Regul Integr Comp Physiol,2010,298(3):R509-516.
[13] DIVAC N, NAUMOVIC R, STOJANOVIC R, et al. The role of immunosuppressive medications in the pathogenesis of hypertension and efficacy and safety of antihypertensive agents in kidney transplant recipients[J]. Curr Med Chem,2016,23(19):1941-1952.
[14] JONES C I. Platelet function and ageing[J]. Mamm Genome,2016,27(7/8):358-366.
[15] SWIGRIS J J, BROWN K K. The role of endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis[J]. BioDrugs,2010,24(1):49-54.
[16] LIU Q, SONG J, LU D, et al. Effects of renal denervation on monocrotaline induced pulmonary remodeling[J]. Oncotarget,2017,8(29):46846-46855.
[2] 苏恩勇,高传玉.内皮功能障碍与心血管疾病关系的研究进展[J].中华实用诊断与治疗杂志,2018,32(6):622-624.
[3] KRUM H, SCHLAICH M P, SOBOTKA P A, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study[J]. Lancet,2014,383(9917):622-629.
[4] BRUNO R M, SUDANO I, GHIADONI L, et al. Interactions between sympathetic nervous system and endogenous endothelin in patients with essential hypertension[J]. Hypertension,2011,57(1):79-84.
[5] LI M W, MIAN M O, BARHOUMI T, et al. Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice[J]. Arterioscler Thromb Vasc Biol,2013,33(10):2306-2315.
[6] BRIONES A M, ARAS-LOPEZ R, ALONSO M J, et al. Small artery remodeling in obesity and insulin resistance[J]. Curr Vasc Pharmacol,2014,12(3):427-437.
[7] 杨晓航,赵林蔚,苏恩勇,等.肾动脉内膜射频消融术对小型猪肾动脉内膜的影响[J].中华实用诊断与治疗杂志,2018,32(5):422-425.
[8] ZHENG L H, SUN W, YAO Y, et al. Associations of big endothelin-1 and C-reactive protein in atrial fibrillation[J]. J Geriatr Cardiol,2016,13(5):465-470.
[9] LU J, LING Z, CHEN W, et al. Effects of renal sympathetic denervation using saline-irrigated radiofrequency ablation catheter on the activity of the renin-angiotensin system and endothelin-1[J]. J Renin Angiotensin Aldosterone Syst,2014,15(4):532-539.
[10] CHEN D D, DONG Y G, YUAN H, et al. Endothelin-1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension[J]. Hypertension,2012,59(5):1037-1043.
[11] MORRIS R, SPENCER S K, KYLE P B, et al. Hypertension in an animal model of HELLP syndrome is associated with activation of endothelin-1[J]. Reprod Sci,2016,23(1):42-50.
[12] LEKONTSEVA O, CHAKRABARTI S, DAVIDGE S T. Endothelin in the female vasculature: a role in aging?[J]. Am J Physiol Regul Integr Comp Physiol,2010,298(3):R509-516.
[13] DIVAC N, NAUMOVIC R, STOJANOVIC R, et al. The role of immunosuppressive medications in the pathogenesis of hypertension and efficacy and safety of antihypertensive agents in kidney transplant recipients[J]. Curr Med Chem,2016,23(19):1941-1952.
[14] JONES C I. Platelet function and ageing[J]. Mamm Genome,2016,27(7/8):358-366.
[15] SWIGRIS J J, BROWN K K. The role of endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis[J]. BioDrugs,2010,24(1):49-54.
[16] LIU Q, SONG J, LU D, et al. Effects of renal denervation on monocrotaline induced pulmonary remodeling[J]. Oncotarget,2017,8(29):46846-46855.