四氢姜黄素对压力负荷引起的小鼠心肌肥厚的保护作用
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摘要
目的探究四氢姜黄素(THC)能否减轻压力负荷引起的成年小鼠病理性心肌肥厚。方法 24只C57BL/6小鼠随机分为4组:假手术(Sham)组、THC组、主动脉弓缩窄(TAC)组及TAC+THC组,每组6只。通过TAC术建立小鼠心肌肥厚模型,Sham组和THC组不结扎主动脉弓。TAC术后每日通过饮水摄入THC(120 mg/kg)。TAC术后4周检测小鼠心脏功能,分离心脏和肺脏计算心脏/体质量比和肺脏/体质量比,HE染色计算心肌细胞平均横截面积,Masson染色观察心脏组织胶原沉积程度,Western blotting检测α-肌球蛋白重链(α-MHC)、β-肌球蛋白重链(β-MHC)蛋白表达,实时定量PCR(real-time PCR)检测心房钠尿肽(ANP)mRNA表达情况。结果 TAC术后4周,小鼠发生病理性心肌肥厚,表现为心脏/体质量比、肺脏/体质量比、心肌细胞平均横截面积、心脏组织胶原沉积、β-MHC和ANP表达较Sham组小鼠明显增高,而左室射血分数(LVEF)、左室短轴缩短率(LVFS)和α-MHC表达较Sham组小鼠明显降低。与TAC组相比,THC处理可以明显缓解TAC引起的病理性心肌肥厚,改善心脏功能,提高α-MHC表达,降低心脏/体质量比、肺脏/体质量比、心肌细胞平均横截面积、心脏组织胶原沉积、β-MHC和ANP表达(均P<0.05)。结论 THC能够有效减轻压力负荷引起的病理性心肌肥厚。
Objective To investigate whether tetrahydrocurcumin(THC) treatment could ameliorate pressure overload-induced cardiac hypertrophy in adult C57BL/6 mice.Methods Twenty-four C57BL/6 mice were randomly divided into four groups(n=6 in each group): the Sham, THC group, transverse aortic constriction(TAC) group, and TAC+THC group. The mice were subjected to TAC to establish the cardiac hypertrophy mouse model. The mice in the Sham and THC groups were subjected to the same procedure without ligating aortic arch. After the procedure, the mice were administered with THC(120mg·kg~(-1)·d~(-1)) through drinking water. Four weeks after TAC surgery, the heart function was detected in mice. The ratios of heart/body weight(HW/BW) and lung/body weight(LW/BW) were calculated, and the mean cross-sectional area of cardiomyocytes was calculated by HE staining. The collagen deposition degree of heart tissue was observed by Masson staining. The protein expression levels of α-myosin heavy chain(α-MHC) and β-myosin heavy chain(β-MHC) were detected by Western blot assay. The expression of atrial natriuretic peptide(ANP) mRNA was detected by real-time PCR(RT-PCR).Results Four weeks after TAC surgery, the mice were presented with symptoms of cardiac hypertrophy,including the increase in HW/BW, LW/BW, the mean cross-sectional area of cardiomyocytes, collagen deposition, the expression levels of β-MHC and ANP, and the decrease in cardiac function and α-MHC expression. Compared with the TAC group, THC treatment could significantly ameliorate pathological cardiac hypertrophy caused by TAC, improve cardiac function, increase α-MHC expression, and decrease HW/BW, LW/BW, the mean cross-sectional area of cardiomyocytes,collagen deposition and the expression levels of β-MHC and ANP(P<0.05).Conclusion THC treatment could effectively attenuate pressure overload-induced pathological cardiac hypertrophy.
Objective To investigate whether tetrahydrocurcumin(THC) treatment could ameliorate pressure overload-induced cardiac hypertrophy in adult C57BL/6 mice.Methods Twenty-four C57BL/6 mice were randomly divided into four groups(n=6 in each group): the Sham, THC group, transverse aortic constriction(TAC) group, and TAC+THC group. The mice were subjected to TAC to establish the cardiac hypertrophy mouse model. The mice in the Sham and THC groups were subjected to the same procedure without ligating aortic arch. After the procedure, the mice were administered with THC(120mg·kg~(-1)·d~(-1)) through drinking water. Four weeks after TAC surgery, the heart function was detected in mice. The ratios of heart/body weight(HW/BW) and lung/body weight(LW/BW) were calculated, and the mean cross-sectional area of cardiomyocytes was calculated by HE staining. The collagen deposition degree of heart tissue was observed by Masson staining. The protein expression levels of α-myosin heavy chain(α-MHC) and β-myosin heavy chain(β-MHC) were detected by Western blot assay. The expression of atrial natriuretic peptide(ANP) mRNA was detected by real-time PCR(RT-PCR).Results Four weeks after TAC surgery, the mice were presented with symptoms of cardiac hypertrophy,including the increase in HW/BW, LW/BW, the mean cross-sectional area of cardiomyocytes, collagen deposition, the expression levels of β-MHC and ANP, and the decrease in cardiac function and α-MHC expression. Compared with the TAC group, THC treatment could significantly ameliorate pathological cardiac hypertrophy caused by TAC, improve cardiac function, increase α-MHC expression, and decrease HW/BW, LW/BW, the mean cross-sectional area of cardiomyocytes,collagen deposition and the expression levels of β-MHC and ANP(P<0.05).Conclusion THC treatment could effectively attenuate pressure overload-induced pathological cardiac hypertrophy.
引文
[1]Zhai M,Liu ZH,Zhang B,et al.Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC-1beta:In vivo and in vitro studies[J].J Pineal Res,2017,63(3):e12433.doi:10.1111/jpi.12433.
[2]Blaustein MP.How does pressure overload cause cardiac hypertrophy and dysfunction?High-ouabain affinity cardiac Na(+)pumps are crucial[J].Am J Physiol Heart Circ Physiol,2017,313(5):H919-H930.doi:10.1152/ajpheart.00131.2017.
[3]Klingbeil AU,Schneider M,Martus P,et al.A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension[J].Am J Med,2003,115(1):41-46.
[4]Yusuf S,Teo KK,Pogue J,et al.Telmisartan,ramipril,or both in patients at high risk for vascular events[J].N Engl J Med,2008,358(15):1547-1559.doi:10.1056/NEJMoa0801317.
[5]Takeuchi S,Kotani Y,Tsujimoto T.Hypotension induced by the concomitant use of a calcium-channel blocker and clarithromycin[J].BMJ Case Rep,2017,2017.pii:bcr2016218388.doi:10.1136/bcr-2016-218388.
[6]Wei G,Chen B,Lin Q,et al.Tetrahydrocurcumin provides neuroprotection in experimental traumatic brain injury and the Nrf2signaling pathway as a potential mechanism[J].Neuroimmunomodulation,2017,24(6):348-355.doi:10.1159/000487998.
[7]Kukongviriyapan U,Apaijit K,Kukongviriyapan V.Oxidative stress and cardiovascular dysfunction associated with cadmium exposure:beneficial effects of curcumin and tetrahydrocurcumin[J].Tohoku JExp Med,2016,239(1):25-38.doi:10.1620/tjem.239.25.
[8]Lai CS,Wu JC,Yu SF,et al.Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis[J].Mol Nutr Food Res,2011,55(12):1819-1828.doi:10.1002/mnfr.201100290.
[9]Bai XJ,Hao JT,Wang J,et al.Curcumin inhibits cardiac hypertrophy and improves cardiovascular function via enhanced Na(+)/Ca(2+)exchanger expression after transverse abdominal aortic constriction in rats[J].Pharmacol Rep,2018,70(1):60-68.doi:10.1016/j.pharep.2017.07.014.
[10]翟蒙恩,李步潆,段维勋,等.小鼠改良微创主动脉弓缩窄模型与经典模型的比较[J].中国体外循环杂志,2015,13(3):174-177.Zhai MN,Li BY,Duan WX,et al.Comparison of modified minimally invasive transverse aortic constriction model and classical model in mice[J].Chinese Journal of Cardiopulmonary,2015,13(3):174-177.doi:10.13498/j.cnki.chin.j.ecc.2015.03.13.
[11]Yang Y,Duan W,Lin Y,et al.SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury[J].Free Radic Biol Med,2013,65:667-679.doi:10.1016/j.freeradbiomed.2013.07.007.
[12]Beetz N,Rommel C,Schnick T,et al.Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload[J].J Mol Cell Cardiol,2016,101:145-155.doi:10.1016/j.yjmcc.2016.10.011.
[13]Clark AL,Coats A,Krum H,et al.Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure:results from the COPERNICUS trial[J].J Cachexia Sarcopenia Muscle,2017,8(4):549-556.doi:10.1002/jcsm.12191.
[14]Xie M,Burchfield JS,Hill JA.Pathological ventricular remodeling:therapies:part 2 of 2[J].Circulation,2013,128(9):1021-1030.doi:10.1161/CIRCULATIONAHA.113.001879.
[15]Florea VG,Rector TS,Anand IS,et al.Heart failure with improved ejection fraction:clinical characteristics,correlates of recovery,and survival:results from the Valsartan Heart Failure Trial[J].Circ Heart Fail,2016,9(7).pii:e003123.doi:10.1161/CIRCHEARTFAILURE.116.003123.
[16]Anand IS,Claggett B,Liu J,et al.Interaction between spironolactone and natriuretic peptides in patients with heart failure and preserved ejection fraction:from the TOPCAT Trial[J].JACCHeart Fail,2017,5(4):241-252.doi:10.1016/j.jchf.2016.11.015.
[17]Delgado-Montero A,Tayal B,Goda A,et al.Additive Prognostic Value of Echocardiographic Global Longitudinal and Global Circumferential Strain to Electrocardiographic Criteria in Patients With Heart Failure Undergoing Cardiac Resynchronization Therapy[J].Circ Cardiovasc Imaging,2016,9(6).pii:e004241.doi:10.1161/CIRCIMAGING.115.004241.
[18]Slaughter MS,Rogers JG,Milano CA,et al.Advanced heart failure treated with continuous-flow left ventricular assist device[J].NEngl J Med,2009,361(23):2241-2251.doi:10.1056/NEJMoa0909938.
[19]Lau WL,Khazaeli M,Savoj J,et al.Dietary tetrahydrocurcumin reduces renal fibrosis and cardiac hypertrophy in 5/6nephrectomized rats[J].Pharmacol Res Perspect,2018,6(2):e385.doi:10.1002/prp2.385.
[20]Ali MS,Mudagal MP,Goli D.Cardioprotective effect of tetrahydrocurcumin and rutin on lipid peroxides and antioxidants in experimentally induced myocardial infarction in rats[J].Pharmazie,2009,64(2):132-136.
[21]Hang CT,Yang J,Han P,et al.Chromatin regulation by Brg1underlies heart muscle development and disease[J].Nature,2010,466(7302):62-67.doi:10.1038/nature09130.
[22]Weiss A,Leinwand LA.The mammalian myosin heavy chain gene family[J].Annu Rev Cell Dev Biol,1996,12:417-439.
[23]Li F,Zhang N,Wu Q,et al.Syringin prevents cardiac hypertrophy induced by pressure overload through the attenuation of autophagy[J].Int J Mol Med,2017,39(1):199-207.doi:10.3892/ijmm.2016.2824.
[24]Miyazaki T,Otani K,Chiba A,et al.A new secretory peptide of natriuretic peptide family,osteocrin,suppresses the progression of congestive heart failure after myocardial infarction[J].Circ Res,2018,122(5):742-751.doi:10.1161/CIRCRESAHA.117.312624.
[25]Moens AL,Takimoto E,Tocchetti CG,et al.Reversal of cardiac hypertrophy and fibrosis from pressure overload by tetrahydrobiopterin:efficacy of recoupling nitric oxide synthase as a therapeutic strategy[J].Circulation,2008,117(20):2626-2636.doi:10.1161/CIRCULATIONAHA.107.737031.
[26]Rockey DC,Bell PD,Hill JA.Fibrosis--a common pathway to organ injury and failure[J].N Engl J Med,2015,372(12):1138-1149.doi:10.1056/NEJMra1300575.
[2]Blaustein MP.How does pressure overload cause cardiac hypertrophy and dysfunction?High-ouabain affinity cardiac Na(+)pumps are crucial[J].Am J Physiol Heart Circ Physiol,2017,313(5):H919-H930.doi:10.1152/ajpheart.00131.2017.
[3]Klingbeil AU,Schneider M,Martus P,et al.A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension[J].Am J Med,2003,115(1):41-46.
[4]Yusuf S,Teo KK,Pogue J,et al.Telmisartan,ramipril,or both in patients at high risk for vascular events[J].N Engl J Med,2008,358(15):1547-1559.doi:10.1056/NEJMoa0801317.
[5]Takeuchi S,Kotani Y,Tsujimoto T.Hypotension induced by the concomitant use of a calcium-channel blocker and clarithromycin[J].BMJ Case Rep,2017,2017.pii:bcr2016218388.doi:10.1136/bcr-2016-218388.
[6]Wei G,Chen B,Lin Q,et al.Tetrahydrocurcumin provides neuroprotection in experimental traumatic brain injury and the Nrf2signaling pathway as a potential mechanism[J].Neuroimmunomodulation,2017,24(6):348-355.doi:10.1159/000487998.
[7]Kukongviriyapan U,Apaijit K,Kukongviriyapan V.Oxidative stress and cardiovascular dysfunction associated with cadmium exposure:beneficial effects of curcumin and tetrahydrocurcumin[J].Tohoku JExp Med,2016,239(1):25-38.doi:10.1620/tjem.239.25.
[8]Lai CS,Wu JC,Yu SF,et al.Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis[J].Mol Nutr Food Res,2011,55(12):1819-1828.doi:10.1002/mnfr.201100290.
[9]Bai XJ,Hao JT,Wang J,et al.Curcumin inhibits cardiac hypertrophy and improves cardiovascular function via enhanced Na(+)/Ca(2+)exchanger expression after transverse abdominal aortic constriction in rats[J].Pharmacol Rep,2018,70(1):60-68.doi:10.1016/j.pharep.2017.07.014.
[10]翟蒙恩,李步潆,段维勋,等.小鼠改良微创主动脉弓缩窄模型与经典模型的比较[J].中国体外循环杂志,2015,13(3):174-177.Zhai MN,Li BY,Duan WX,et al.Comparison of modified minimally invasive transverse aortic constriction model and classical model in mice[J].Chinese Journal of Cardiopulmonary,2015,13(3):174-177.doi:10.13498/j.cnki.chin.j.ecc.2015.03.13.
[11]Yang Y,Duan W,Lin Y,et al.SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury[J].Free Radic Biol Med,2013,65:667-679.doi:10.1016/j.freeradbiomed.2013.07.007.
[12]Beetz N,Rommel C,Schnick T,et al.Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload[J].J Mol Cell Cardiol,2016,101:145-155.doi:10.1016/j.yjmcc.2016.10.011.
[13]Clark AL,Coats A,Krum H,et al.Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure:results from the COPERNICUS trial[J].J Cachexia Sarcopenia Muscle,2017,8(4):549-556.doi:10.1002/jcsm.12191.
[14]Xie M,Burchfield JS,Hill JA.Pathological ventricular remodeling:therapies:part 2 of 2[J].Circulation,2013,128(9):1021-1030.doi:10.1161/CIRCULATIONAHA.113.001879.
[15]Florea VG,Rector TS,Anand IS,et al.Heart failure with improved ejection fraction:clinical characteristics,correlates of recovery,and survival:results from the Valsartan Heart Failure Trial[J].Circ Heart Fail,2016,9(7).pii:e003123.doi:10.1161/CIRCHEARTFAILURE.116.003123.
[16]Anand IS,Claggett B,Liu J,et al.Interaction between spironolactone and natriuretic peptides in patients with heart failure and preserved ejection fraction:from the TOPCAT Trial[J].JACCHeart Fail,2017,5(4):241-252.doi:10.1016/j.jchf.2016.11.015.
[17]Delgado-Montero A,Tayal B,Goda A,et al.Additive Prognostic Value of Echocardiographic Global Longitudinal and Global Circumferential Strain to Electrocardiographic Criteria in Patients With Heart Failure Undergoing Cardiac Resynchronization Therapy[J].Circ Cardiovasc Imaging,2016,9(6).pii:e004241.doi:10.1161/CIRCIMAGING.115.004241.
[18]Slaughter MS,Rogers JG,Milano CA,et al.Advanced heart failure treated with continuous-flow left ventricular assist device[J].NEngl J Med,2009,361(23):2241-2251.doi:10.1056/NEJMoa0909938.
[19]Lau WL,Khazaeli M,Savoj J,et al.Dietary tetrahydrocurcumin reduces renal fibrosis and cardiac hypertrophy in 5/6nephrectomized rats[J].Pharmacol Res Perspect,2018,6(2):e385.doi:10.1002/prp2.385.
[20]Ali MS,Mudagal MP,Goli D.Cardioprotective effect of tetrahydrocurcumin and rutin on lipid peroxides and antioxidants in experimentally induced myocardial infarction in rats[J].Pharmazie,2009,64(2):132-136.
[21]Hang CT,Yang J,Han P,et al.Chromatin regulation by Brg1underlies heart muscle development and disease[J].Nature,2010,466(7302):62-67.doi:10.1038/nature09130.
[22]Weiss A,Leinwand LA.The mammalian myosin heavy chain gene family[J].Annu Rev Cell Dev Biol,1996,12:417-439.
[23]Li F,Zhang N,Wu Q,et al.Syringin prevents cardiac hypertrophy induced by pressure overload through the attenuation of autophagy[J].Int J Mol Med,2017,39(1):199-207.doi:10.3892/ijmm.2016.2824.
[24]Miyazaki T,Otani K,Chiba A,et al.A new secretory peptide of natriuretic peptide family,osteocrin,suppresses the progression of congestive heart failure after myocardial infarction[J].Circ Res,2018,122(5):742-751.doi:10.1161/CIRCRESAHA.117.312624.
[25]Moens AL,Takimoto E,Tocchetti CG,et al.Reversal of cardiac hypertrophy and fibrosis from pressure overload by tetrahydrobiopterin:efficacy of recoupling nitric oxide synthase as a therapeutic strategy[J].Circulation,2008,117(20):2626-2636.doi:10.1161/CIRCULATIONAHA.107.737031.
[26]Rockey DC,Bell PD,Hill JA.Fibrosis--a common pathway to organ injury and failure[J].N Engl J Med,2015,372(12):1138-1149.doi:10.1056/NEJMra1300575.