NPR-A在压力超负荷性大鼠心肌重构过程中的表达变化
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摘要
目的观察在A型利钠肽受体(NPR-A)表达压力超负荷性大鼠心肌重构过程中的变化,探讨其在高血压心肌重构过程中的可能作用。方法 40只清洁级SD大鼠随机分为对照组(20只)及模型组(20只),模型组采用"两肾一夹法"构建肾性高血压大鼠模型,术后每周测尾动脉收缩压(SBP),于术后4、8周后处死大鼠。计算左心室重量指数(LVMI),采用HE、天狼星红染色观察左心室病理形态学变化,采用ELLSA法测定血浆脑钠肽(BNP),免疫组化测定左心室NPR-A蛋白表达水平。比较两组SBP、LVMI、心肌细胞直径(MD)、心肌组织胶原容积分数(CVF)、BNP及NPR-A蛋白表达水平。结果模型组大鼠术后4、8周后SBP、LVMI、MD、CVF均明显高于对照组(均P<0.05);模型组大鼠术后4周血浆BNP、左心室NPR-A表达水平均明显升高(P<0.05),术后8周血浆BNP明显升高(P<0.05),左心室NPR-A水平明显下降(P<0.05)。与模型组术后4周相比,模型组大鼠术后8周尾动脉SBP无明显变化(P>0.05),但LVMI、MD、CVF均显著升高,血浆BNP水平显著升高,左心室NPR-A表达显著下降,差异均有统计学意义(均P<0.05)。结论压力超负荷性大鼠左心室NPR-A的表达呈动态变化趋势,可能参与高血压心肌重构发生发展的过程。
Objective To observe the changes of NPR-A expression in the process of myocardial remodeling in stress-overloaded rats and explore its possible role. Methods 40 clean-grade SD rats were randomly divided into sham operation Group(n=20) and model group(n=20).The rat model of renal hypertension was established by two-kidney one-clip method in the model group.Tail artery systolic pressure(SBP) was measured every week after surgery,and rats were killed at 4 and 8 weekends after operation.The left ventricular weight index(LVMI) was calculated.The pathological morphology of left ventricle was observed by HE and Sirius Red staining,plasma brain natriuretic peptide was observes by enzyme-linked immunosorbent assay(ELISA),and the expression level of NPR-A protein in left ventricular observed by immunohistochemical.The SBP,LVMI,myocyte diameter(MD),collagen volume fraction(CVF),the expression of BNP and NPR-A of two groups were compared. Results Compared with corresponding sham operation group,the level of SBP,LVMI,MD,and CVF in model group were significantly increased(P<0.05).The level of plasma BNP and left ventricular NPR-A in model group at the 4 th week post-operation was significantly higher than corresponding sham operation group(P<0.05).Compared with corresponding sham operation group,the level of plasma BNP in model group at the 8 th week post-operation was significantly higher(P<0.05),while the level of left ventricular NPR-A in model group at the 8 th week post-operation was lower significantly(P<0.05).Compared with model group at the 4 th week post-operation,the level of Tail artery BP in model group at the 8 th week post-operation was not greatly changed(P>0.05),while the level of LVMI,MD,CVF increased significantly(P<0.05).The level of plasma BNP was significantly higher,while the level of left ventricular NPR-A was significantly lower in model group at the 8 th week post-operation than those of model group at the 4 th week post-operation(P<0.05). Conclusion The expression of left ventricular NPR-A in stress-overloaded rats showed dynamic changes,which may be involved in the occurrence and development of hypertensive myocardial remodeling.
Objective To observe the changes of NPR-A expression in the process of myocardial remodeling in stress-overloaded rats and explore its possible role. Methods 40 clean-grade SD rats were randomly divided into sham operation Group(n=20) and model group(n=20).The rat model of renal hypertension was established by two-kidney one-clip method in the model group.Tail artery systolic pressure(SBP) was measured every week after surgery,and rats were killed at 4 and 8 weekends after operation.The left ventricular weight index(LVMI) was calculated.The pathological morphology of left ventricle was observed by HE and Sirius Red staining,plasma brain natriuretic peptide was observes by enzyme-linked immunosorbent assay(ELISA),and the expression level of NPR-A protein in left ventricular observed by immunohistochemical.The SBP,LVMI,myocyte diameter(MD),collagen volume fraction(CVF),the expression of BNP and NPR-A of two groups were compared. Results Compared with corresponding sham operation group,the level of SBP,LVMI,MD,and CVF in model group were significantly increased(P<0.05).The level of plasma BNP and left ventricular NPR-A in model group at the 4 th week post-operation was significantly higher than corresponding sham operation group(P<0.05).Compared with corresponding sham operation group,the level of plasma BNP in model group at the 8 th week post-operation was significantly higher(P<0.05),while the level of left ventricular NPR-A in model group at the 8 th week post-operation was lower significantly(P<0.05).Compared with model group at the 4 th week post-operation,the level of Tail artery BP in model group at the 8 th week post-operation was not greatly changed(P>0.05),while the level of LVMI,MD,CVF increased significantly(P<0.05).The level of plasma BNP was significantly higher,while the level of left ventricular NPR-A was significantly lower in model group at the 8 th week post-operation than those of model group at the 4 th week post-operation(P<0.05). Conclusion The expression of left ventricular NPR-A in stress-overloaded rats showed dynamic changes,which may be involved in the occurrence and development of hypertensive myocardial remodeling.
引文
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[12] Tonne JM,Holditch SJ,Oehler EA,et al.Cardiac BNP gene delivery prolongs survival in aged spontaneously hypertensive rats with overt hypertensive heart disease [J].Aging,2014,6(4):311-319.
[13] Kishimoto I,Rossi K,Garbers DL.A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy [J].Proc Natl Acad Sci USA,2001,98(5):2703-2706.
[14] Kishimoto I,Tokudome T,Horio T,et al.Natriuretic Peptide Signaling via Guanylyl Cyclase (GC)-A:An Endogenous Protective Mechanism of the Heart [J].Curr Cardiol Rev,2009,5(1):45-51.
[2] 林璋,洪华山,林军华,等.石蜡切片行免疫荧光染色后再行PAS或HE染色确定NPR-A蛋白在肾脏的定位[J].中国组织化学与细胞化学杂志,2012,21(3):279-283.
[3] Pandey KN.Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes phosphoinositide hydrolysis,Ca2+ release,and activation of protein kinase C [J].Front Mol Neurosc,2014,(7):75.
[4] 肾去交感神经术对异丙肾上腺素诱发的慢性心功能不全大鼠左心房心肌纤维化的影响[J].中华心血管病杂志,2015,43(12):1040-1045.
[5] Wei T,Zeng C,Chen L,et al.Bedside tests of B-type natriuretic peptide in the diagnosis of left ventricular diastolic dysfunction in hypertensive patients [J].Eur J Heart Fail,2014,7(1):75-79.
[6] 冯梅,滕文浩,姜雯雯,等.表皮生长因子受体在肾血管性高血压大鼠心血管重构中的作用[J].中国药理学通报,2016,32(5):625-631.
[7] 黄鑫涛,洪华山,李小红,等.替米沙坦对糖尿病高血压大鼠肾内小动脉重构的影响[J].中国循证心血管医学杂志,2015,7(6):821-826.
[8] Nwokocha CR,Ozolua RI,Owu DU,et al.Antihypertensive properties of Allium sativum (garlic) on normotensive and two kidney one clip hypertensive rats [J].Niger J Physiol Sci,2014,26(2):213-218.
[9] Yu CM,Sanderson JE.Plasma brain natriuretic peptide-an independent predictor of cardiovascular mortality in acute heart failure [J].Eur J Heart Fail,2014,1(1):59-65.
[10] Suo M,Hautala N,F?ldes G,et al.Posttranscriptional Control of BNP Gene Expression in Angiotensin II-Induced Hypertension [J].Hypertension,2002,39(3):803-808.
[11] Gopi V,Subramanian V,Manivasagam S,et al.Angiotensin II down-regulates natriuretic peptide receptor-A expression and guanylyl cyclase activity in H9c2 (2-1) cardiac myoblast cells:Role of ROS and NF-κB [J].Mol Cell Biochem,2015,409(1-2):67-79.
[12] Tonne JM,Holditch SJ,Oehler EA,et al.Cardiac BNP gene delivery prolongs survival in aged spontaneously hypertensive rats with overt hypertensive heart disease [J].Aging,2014,6(4):311-319.
[13] Kishimoto I,Rossi K,Garbers DL.A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy [J].Proc Natl Acad Sci USA,2001,98(5):2703-2706.
[14] Kishimoto I,Tokudome T,Horio T,et al.Natriuretic Peptide Signaling via Guanylyl Cyclase (GC)-A:An Endogenous Protective Mechanism of the Heart [J].Curr Cardiol Rev,2009,5(1):45-51.