高盐饮食对自发性高血压大鼠肾脏的影响及左旋氨氯地平的作用
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摘要
目的观察高盐饮食对自发性高血压大鼠肾脏的影响及左旋氨氯地平的干预作用。方法自发性高血压大鼠30只,随机分为3组:正常盐组(含0.4%Na Cl饲料喂养,n=10)、高盐组(含4%Na Cl饲料喂养,n=10)、高盐+左旋氨氯地平干预组(含4%Na Cl饲料喂养+左旋氨氯地平灌胃,n=10),喂养14周。尾动脉测压仪测量尾动脉收缩压。14周时摘取双层肾脏计算双肾肥大指数,HE、Masson染色观察肾脏形态学改变,免疫组化法检测肾脏组织转化生长因子-β1(TGF-β1)表达。结果与正常盐组相比,高盐组大鼠收缩压第6周时明显升高(P<0.05),高盐+左旋氨氯地平干预组收缩压低于正常盐组和高盐组(P<0.05)。与正常盐组相比,高盐组、高盐+左旋氨氯地平组的双肾肥大指数显著增高(P<0.05)。高盐组肾小球球囊黏连、肾小管间质纤维化。免疫组化结果显示,高盐组肾脏组织TGF-β1的表达高于正常盐组,而高盐+氨氯地平组肾脏组织TGF-β1表达较另外两组低。结论长期高盐饮食可引起自发性高血压大鼠血压升高、肾小球球囊黏连、肾小管间质纤维化。高盐饮食所致自发性高血压大鼠肾纤维化可能与TGF-β1的过表达有关。左旋氨氯地平能有效降压、减少肾纤维化,可能与降低TGF-β1的过表达有关。
Objective To observe the effect of high salt diet on the kidney in spontaneously hypertensive rats and the intervention effect of L-amlodipine. Methods Thirty spontaneously hypertensive rats were randomly divided into 3 groups: normal salt group(fed with 0.4% NaCl, n=10), high salt group(fed with 0.4% NaCl, n=10),high salt + L-amlodipine intervention group(fed with 0.4% NaCl+ L-amlodipine by gavage, n=10), fed for 14 weeks. The systolic pressure of the tail artery was measured by the tail-artery blood pressure-measuring instrument.At the 14 th week, the double kidneys were taken to calculate the double kidney hypertrophy index. HE and Masson staining were used to observe the morphological changes of the kidney. The expression of TGF-β1 in the kidney tissue was detected by the immunohistochemical method. Results Compared with the normal salt group, the systolic blood pressure of the high salt group was significantly higher at the sixth week(P<0.05). The high salt + L-amlodipine intervention group had lower systolic blood pressure than the normal and high salt groups(P<0.05). Compared with the normal salt group, the double kidneys hypertrophy index of the high salt group and the high salt + L-amlodipine group was significantly increased(P<0.05). The high salt group had glomerular balloon adhesion, tubulointerstitial fibrosis. The results of immunohistochemistry showed that the expression of TGF-β1 in the kidney tissue of the high salt group was higher than that of the normal salt group, while the expression of TGF-β1 in the kidney tissue of the high salt + L-amlodipine group was lower than that of the other two groups. Conclusion Long-term high salt diet can cause elevated blood pressure, glomerular balloon adhesion, and tubulointerstitial fibrosis in spontaneously hypertensive rats. Renal fibrosis in spontaneously hypertensive rats induced by high salt diet may be related to overexpression of TGF-β1. L-amlodipine can effectively reduce blood pressure and reduce renal fibrosis, which may be related to the reduction of the overexpression of TGF-β1.
Objective To observe the effect of high salt diet on the kidney in spontaneously hypertensive rats and the intervention effect of L-amlodipine. Methods Thirty spontaneously hypertensive rats were randomly divided into 3 groups: normal salt group(fed with 0.4% NaCl, n=10), high salt group(fed with 0.4% NaCl, n=10),high salt + L-amlodipine intervention group(fed with 0.4% NaCl+ L-amlodipine by gavage, n=10), fed for 14 weeks. The systolic pressure of the tail artery was measured by the tail-artery blood pressure-measuring instrument.At the 14 th week, the double kidneys were taken to calculate the double kidney hypertrophy index. HE and Masson staining were used to observe the morphological changes of the kidney. The expression of TGF-β1 in the kidney tissue was detected by the immunohistochemical method. Results Compared with the normal salt group, the systolic blood pressure of the high salt group was significantly higher at the sixth week(P<0.05). The high salt + L-amlodipine intervention group had lower systolic blood pressure than the normal and high salt groups(P<0.05). Compared with the normal salt group, the double kidneys hypertrophy index of the high salt group and the high salt + L-amlodipine group was significantly increased(P<0.05). The high salt group had glomerular balloon adhesion, tubulointerstitial fibrosis. The results of immunohistochemistry showed that the expression of TGF-β1 in the kidney tissue of the high salt group was higher than that of the normal salt group, while the expression of TGF-β1 in the kidney tissue of the high salt + L-amlodipine group was lower than that of the other two groups. Conclusion Long-term high salt diet can cause elevated blood pressure, glomerular balloon adhesion, and tubulointerstitial fibrosis in spontaneously hypertensive rats. Renal fibrosis in spontaneously hypertensive rats induced by high salt diet may be related to overexpression of TGF-β1. L-amlodipine can effectively reduce blood pressure and reduce renal fibrosis, which may be related to the reduction of the overexpression of TGF-β1.
引文
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[11]Kaynar K,Ulusoy S,Ovali E,et al.TGF-b and TNF-a producing effects of losartan and amlodipine on human mononuclear cell culture[J].Nephrology 2005,10:478-82.
[12]Habibi J,Hayden MR,Ferrario CM,et al.Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats[J].Cardiorenal Med,2014,4:43-52.
[13]MC.Fiore,PM Jimenez,Cremonezzi,et al.Statins reverse renal inflammation and endothelial dysfunction induced by chronic high salt intake[J].AJP-Renal Physiol,2011,301(2):F263-F270.
[14]Hovater MB,Sanders PW.Effect of dietary salt on regulation of TGF-βin the kidney[J].Semin Nephrol,2012 May,32(3):269-7.
[15]Liu LL,Li QX,Xix L,et al.Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats[J].Toxicology 2007,231:81-90.
[16]Lai YM,Fukuda N,Su JZ,et al.Novel mechanisms of the antiproliferative effects of amlodipine in vascular smooth muscle cells from spontaneously hypertensive rats[J].Hypertens Res 2002,25:109-15.
[17]Kaynar K,Ulusoy S,Ovali E,et al.TGF-b and TNF-a producing effects of losartan and amlodipine on human mononuclear cell culture[J].Nephrology,2005,10:478-82.
[18]Yun JS,Jin L,Xian FX,et al.Effects of amlodipine on TGF-b-induced Smad2,4 expressions in adriamycin toxicity of rat mesangial cells[J].Arch Toxicol(2011)85:663-8.
[19]Derosa G,Cicero AF,Carbone A,et al.Variation of some inflammatory markers in hypertensive patients after 1 year of olmesartan/amlodipine single-pill combination compared with olmesartan or amlodipine monotherapies[J].J Am Soc Hypertens,2013Jan,7(1):32-9.
[2]Zhenqiang Bi.Hypertension Prevalence,Awareness,Treatment,and Control and Sodium Intake in Shandong Province,China:Baseline Results From ShandongMinistry of Health Action on Salt Reduction and Hypertension(SMASH),2011[J].Prev Chronic Dis,2014,11:E88:1-15.
[3]Jens J.Salt and obesity revisited[J].J Hypertens.2013(11):2130-2.
[4]Habibi J,Hayden MR,Ferrario CM,et al.Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats[J].Cardiorenal Med,2014,4:43-52.
[5]谢盛彬,王伟铭,陈楠.UUO模型大鼠肾间质纤维化动态进展及α-SMA、TGF-β1和VDR表达变化[J].上海交通大学学报(医学版).2010(7),30:752-7.
[6]Ying WZ,Aaron K,Sanders PW.Mechanism of dietary salt-mediated increase in intravascular production of TGF-β1[J].Am J PhysiolRenal,2008,8:F406-F414.
[7]Cheng J,Grande JP.Transforming growth factor-beta signal transduction and progressive renal disease[J].Exp Biol Med2002,227:943-56.
[8]Dinko Susic,Edward D Frohlich,Hiroyuki Kobori,et al.Salt-induced renal injury in SHRs is mediated by AT1 receptor activation[J].JHypertens.2011 Apr;29(4):716-23.
[9]Huang XR,Chung CK,Wang XJ,et al.Mice overexpressing latent TGF-b1 are protected against renal fibrosis in obstructive kidney disease[J].Am J Physiol-Renal,2008,295:118-27.
[10]Border WA,Noble NA.Evidence that TGF-b should be a therapeutic target in diabetic nephropathy[J].Kidney Int 1998,54:1390-1.
[11]Kaynar K,Ulusoy S,Ovali E,et al.TGF-b and TNF-a producing effects of losartan and amlodipine on human mononuclear cell culture[J].Nephrology 2005,10:478-82.
[12]Habibi J,Hayden MR,Ferrario CM,et al.Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats[J].Cardiorenal Med,2014,4:43-52.
[13]MC.Fiore,PM Jimenez,Cremonezzi,et al.Statins reverse renal inflammation and endothelial dysfunction induced by chronic high salt intake[J].AJP-Renal Physiol,2011,301(2):F263-F270.
[14]Hovater MB,Sanders PW.Effect of dietary salt on regulation of TGF-βin the kidney[J].Semin Nephrol,2012 May,32(3):269-7.
[15]Liu LL,Li QX,Xix L,et al.Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats[J].Toxicology 2007,231:81-90.
[16]Lai YM,Fukuda N,Su JZ,et al.Novel mechanisms of the antiproliferative effects of amlodipine in vascular smooth muscle cells from spontaneously hypertensive rats[J].Hypertens Res 2002,25:109-15.
[17]Kaynar K,Ulusoy S,Ovali E,et al.TGF-b and TNF-a producing effects of losartan and amlodipine on human mononuclear cell culture[J].Nephrology,2005,10:478-82.
[18]Yun JS,Jin L,Xian FX,et al.Effects of amlodipine on TGF-b-induced Smad2,4 expressions in adriamycin toxicity of rat mesangial cells[J].Arch Toxicol(2011)85:663-8.
[19]Derosa G,Cicero AF,Carbone A,et al.Variation of some inflammatory markers in hypertensive patients after 1 year of olmesartan/amlodipine single-pill combination compared with olmesartan or amlodipine monotherapies[J].J Am Soc Hypertens,2013Jan,7(1):32-9.