Effect of Shenqi Yangxin decoction on high mobility group box 1and inflammatory signal pathway in a rat model of dilated cardiomyopathy
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摘要
OBJECTIVE: To investigate the effects of Shenqi Yangxin decoction(SQYXD) on heart function in a rat model of dilated cardiomyopathy(DCM) and its potential mechanisms.METHODS: Sprague-Dawley rats were randomly divided into normal(10 rats) and DCM(150 rats)groups. DCM was induced by an intraperitoneal injection of adriamycin. Then, DCM baseline group was randomly selected sixteen DCM rats. The remaining DCM rats were randomly divided into DCM control, perindopril, metoprolol, and SQYXD groups. Cardiac function and histological analysis plus biochemical measurement of serum levels of brain natriuretic peptide(BNP), and inflammatory factors were measured. The mRNA and protein expression levels of high-mobility group box 1(HMGB1), Toll-like receptor 4(TLR-4), receptor for advanced glycation end products(RAGE), and nuclear factor-κB(NF-κB) were determined. Myocardial metabolism imaging was performed on the normal, SQYXD and DCM control groups to evaluate the effectiveness of treatments.RESULTS: Rats in the DCM control group exhibited dilated left ventricular diameter, impaired cardiac function, disorganized sarcomere, impaired glucose metabolism, increased heart weight index,and increased levels of BNP, which were improved by treatment with SQYXD. In addition, hearts from rats in the DCM baseline group exhibited significantly higher levels of HMGB1, TLR-4, RAGE, NF-κB,tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-10, compared with the normal group. Interestingly, the mRNA level of HMGB1 in the DCM baseline group was positively correlated with that of TLR-4, RAGE, NF-κB, BNP, and LVEDD,but negatively correlated with LVEF. SQYXD inhibited the upregulation of HMGB1 expression and its downstream inflammatory factors.CONCLUSION: Shenqi Yangxin decoction effectively reduced the dilated left ventricular diameter and improved heart function in dilated cardiomyopathy. The mechanisms underlying the action on DCM involve regulating the gene and protein expression of HMGB1 and its inflammatory signal pathways in the DCM rat model.
OBJECTIVE: To investigate the effects of Shenqi Yangxin decoction(SQYXD) on heart function in a rat model of dilated cardiomyopathy(DCM) and its potential mechanisms.METHODS: Sprague-Dawley rats were randomly divided into normal(10 rats) and DCM(150 rats)groups. DCM was induced by an intraperitoneal injection of adriamycin. Then, DCM baseline group was randomly selected sixteen DCM rats. The remaining DCM rats were randomly divided into DCM control, perindopril, metoprolol, and SQYXD groups. Cardiac function and histological analysis plus biochemical measurement of serum levels of brain natriuretic peptide(BNP), and inflammatory factors were measured. The mRNA and protein expression levels of high-mobility group box 1(HMGB1), Toll-like receptor 4(TLR-4), receptor for advanced glycation end products(RAGE), and nuclear factor-κB(NF-κB) were determined. Myocardial metabolism imaging was performed on the normal, SQYXD and DCM control groups to evaluate the effectiveness of treatments.RESULTS: Rats in the DCM control group exhibited dilated left ventricular diameter, impaired cardiac function, disorganized sarcomere, impaired glucose metabolism, increased heart weight index,and increased levels of BNP, which were improved by treatment with SQYXD. In addition, hearts from rats in the DCM baseline group exhibited significantly higher levels of HMGB1, TLR-4, RAGE, NF-κB,tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-10, compared with the normal group. Interestingly, the mRNA level of HMGB1 in the DCM baseline group was positively correlated with that of TLR-4, RAGE, NF-κB, BNP, and LVEDD,but negatively correlated with LVEF. SQYXD inhibited the upregulation of HMGB1 expression and its downstream inflammatory factors.CONCLUSION: Shenqi Yangxin decoction effectively reduced the dilated left ventricular diameter and improved heart function in dilated cardiomyopathy. The mechanisms underlying the action on DCM involve regulating the gene and protein expression of HMGB1 and its inflammatory signal pathways in the DCM rat model.
OBJECTIVE: To investigate the effects of Shenqi Yangxin decoction(SQYXD) on heart function in a rat model of dilated cardiomyopathy(DCM) and its potential mechanisms.METHODS: Sprague-Dawley rats were randomly divided into normal(10 rats) and DCM(150 rats)groups. DCM was induced by an intraperitoneal injection of adriamycin. Then, DCM baseline group was randomly selected sixteen DCM rats. The remaining DCM rats were randomly divided into DCM control, perindopril, metoprolol, and SQYXD groups. Cardiac function and histological analysis plus biochemical measurement of serum levels of brain natriuretic peptide(BNP), and inflammatory factors were measured. The mRNA and protein expression levels of high-mobility group box 1(HMGB1), Toll-like receptor 4(TLR-4), receptor for advanced glycation end products(RAGE), and nuclear factor-κB(NF-κB) were determined. Myocardial metabolism imaging was performed on the normal, SQYXD and DCM control groups to evaluate the effectiveness of treatments.RESULTS: Rats in the DCM control group exhibited dilated left ventricular diameter, impaired cardiac function, disorganized sarcomere, impaired glucose metabolism, increased heart weight index,and increased levels of BNP, which were improved by treatment with SQYXD. In addition, hearts from rats in the DCM baseline group exhibited significantly higher levels of HMGB1, TLR-4, RAGE, NF-κB,tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-10, compared with the normal group. Interestingly, the mRNA level of HMGB1 in the DCM baseline group was positively correlated with that of TLR-4, RAGE, NF-κB, BNP, and LVEDD,but negatively correlated with LVEF. SQYXD inhibited the upregulation of HMGB1 expression and its downstream inflammatory factors.CONCLUSION: Shenqi Yangxin decoction effectively reduced the dilated left ventricular diameter and improved heart function in dilated cardiomyopathy. The mechanisms underlying the action on DCM involve regulating the gene and protein expression of HMGB1 and its inflammatory signal pathways in the DCM rat model.
引文
1 Yuko I,Hitomi O,Osamu S,Shigeo W.Blockade of sarcolemmal TRPV2 accumulation inhibits progression of dilated cardiomyopathy.Cardiovasc Res 2013;99(4)760-768.
2 24 professional and 104 Chinese medicine disease treatment programs,cardiopulmonary disease(dilated cardiomyopathy)Traditional Chinese Medicine treatment program State Administration of Traditional Chinese Medicine,2012:60-65.
3 Shen LJ,Lu S,Zhou YH,LI L,Xing QM,Xu YL.Developing a rat model of dilated cardiomyopathy with improved survival.J Zhejiang Univ-Sci B(Biomed&Biotechnol)2016;17(12):975-983.
4 Wang LC,Ma H,He JG,et al.Effects of perindopril on calcium transients and its regulatory proteins in cardiomyocytes of rats with heart failure.Zhong Hua Xin Xue Guan Bing Za Zhi 2005;33(6):513-517.
5 Ahmet I,Morrell C,Lakatta EG,Talan MI.Therapeutic efficacy of a combination of aβ1-adrenoreceptor(ar)blocker andβ2-ar agonist in a rat model of postmyocardial infarction dilated heart failure exceeds that of aβ1-ARblocker plus angiotensin-converting enzyme inhibitor.JPharmacol Exp Ther 2009;331(1):178-185.
6 Chen Q.Traditional Chinese medicine pharmacologica experimental method.Beijing:People's Health Publishing House,1993:1103.
7 Zhou ML,Shi JX,Hang CH,Zhang,FF,Gao,J,Yin HX.Expression of Toll-like receptor 4 in the brain in a rabbit experimental subarachnoid haemorrhage model.Inflamm Res 2007;56(3):93-97.
8 Shen HX.Molecular biology experimental methods and techniques.Guangzhou:Zhongshan University Press2010:214-228.
9 Sun T,Zhou J,Chen XH,Tang ZD,Jin YQ.The correlation of serum levels of BNP with ventricular remodeling in patients with heart failure of dilated cardiomyopathy.YXue Yan Jiu Za Zhi 2012;41(4):62-64.
10 Todica A,Brunner S,Boning G,et al.[68Ga]-albumin-PET in the Monitoring of left ventricular function in murine models of ischemic and dilated cardiomyopathy comparison with cardiac MRI.Mol Imaging Biol 2013;15(4):441-449.
11 Uebleis C,Hellweger S,Laubender RP,et al.The amoun of dysfunctional but viable myocardium predicts longterm survival in patients with ischemic cardiomyopathy and left ventricular dysfunction.Int J Cardiovasc Imaging2013;29(7):1645-1653.
12 Brunner S,Todica A,B?ning G,et al.Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using[18 F]FDG-PET:comparison with cardiac MRI and monitoring erythropoietin therapy.Ejnmmi Res 2012;2(1):43-51.
13 Shen LJ,Lu S,Zhou YH,et al.Application of 18fluorodeoxyglucose fluorodeoxyglucose miniature positron emission tomography myocardial metabolic imaging in evaluating the rats model of dilated cardiomyopathy.Zhong Guo Xun Huan Za Zhi 2016;31(8):802-806.
14 Zhou YB,Zhang LL,Gao YJ,Zhou YB.Effects of Yiqi Yangyin,Huoxue Huayu decoction on cardiomyocyte apoptosis in experimental viral dilated cardiomyopathy mice.Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi2008;6(5):540-541.
15 Scaffidi P,Misteli T,Bianchi ME.Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.Nature2002;418(6894):191-195.
16 Vande Walle,Kanneganti TD,Lamkanfi M.HMGB1 release by inflammasomes.Virulence2011;2(2):162-165.
17 RoseNR.Myoearditis:infection versus autoimmunity.JClin Immunol 2009;29(6):730-737.
18 Eriksson U,Kurrer MO,Sehmitz N,et al.Interleukin-6-defieient mice resist development of autoimmune myoearditis assoeiated with impaired upregulation of complement C3.Circulation 2003;107(2):320-325.
19 Souza AW,Westra J,Limburg PC,Bijl M,Kallenberg CG.HMGB1 in vascular diseases:Its role in vascular inflammation and atherosclerosis.Autoimmun Rev 2012;11(12):909-917.
20 Volz HC,Laohachewin D,Schellberg D,et al.HMGB1is an independent predictor of death and heart transplantation in heart failure.Clin Res Cardiol 2012;101(6):427-435.
21 Tzeng HP,Fan J,Vallejo JG,et al.Negative inotropic effects of high-mobility group box 1 protein in isolated contracting cardiac myocytes.Am J Physiol Heart Circ Physiol 2008;294(3):H1490-H1496.
22 Wu H,Yang J,Ding JW,et al.Expression of high mobility group protein B,interleukin-6 and tumor necrosis factor in patients with dilated cardiomyopathy.Lin Chuang Xin Xue Guan Bing Za Zhi 2013;29(2):88-90.
23 T Ohtsuka,M Hamada,H Saeki,et al.Comparison of effects of carvedilol versus metoprolol on cytokine levels in patients with idiopathic dilated cardiomyopathy.Am JCardiol 2002;89(8):996-999.
24 Liu C,Song YM,Huang L,Li AM,Geng SH,Yu XJ.Effects of valsartan and perindopril on cytokines and myocardial fibrosis in patients with congestive heart failure.Di San Jun Yi Da Xue Xue Bao 2008;30(12):1189-1192.
2 24 professional and 104 Chinese medicine disease treatment programs,cardiopulmonary disease(dilated cardiomyopathy)Traditional Chinese Medicine treatment program State Administration of Traditional Chinese Medicine,2012:60-65.
3 Shen LJ,Lu S,Zhou YH,LI L,Xing QM,Xu YL.Developing a rat model of dilated cardiomyopathy with improved survival.J Zhejiang Univ-Sci B(Biomed&Biotechnol)2016;17(12):975-983.
4 Wang LC,Ma H,He JG,et al.Effects of perindopril on calcium transients and its regulatory proteins in cardiomyocytes of rats with heart failure.Zhong Hua Xin Xue Guan Bing Za Zhi 2005;33(6):513-517.
5 Ahmet I,Morrell C,Lakatta EG,Talan MI.Therapeutic efficacy of a combination of aβ1-adrenoreceptor(ar)blocker andβ2-ar agonist in a rat model of postmyocardial infarction dilated heart failure exceeds that of aβ1-ARblocker plus angiotensin-converting enzyme inhibitor.JPharmacol Exp Ther 2009;331(1):178-185.
6 Chen Q.Traditional Chinese medicine pharmacologica experimental method.Beijing:People's Health Publishing House,1993:1103.
7 Zhou ML,Shi JX,Hang CH,Zhang,FF,Gao,J,Yin HX.Expression of Toll-like receptor 4 in the brain in a rabbit experimental subarachnoid haemorrhage model.Inflamm Res 2007;56(3):93-97.
8 Shen HX.Molecular biology experimental methods and techniques.Guangzhou:Zhongshan University Press2010:214-228.
9 Sun T,Zhou J,Chen XH,Tang ZD,Jin YQ.The correlation of serum levels of BNP with ventricular remodeling in patients with heart failure of dilated cardiomyopathy.YXue Yan Jiu Za Zhi 2012;41(4):62-64.
10 Todica A,Brunner S,Boning G,et al.[68Ga]-albumin-PET in the Monitoring of left ventricular function in murine models of ischemic and dilated cardiomyopathy comparison with cardiac MRI.Mol Imaging Biol 2013;15(4):441-449.
11 Uebleis C,Hellweger S,Laubender RP,et al.The amoun of dysfunctional but viable myocardium predicts longterm survival in patients with ischemic cardiomyopathy and left ventricular dysfunction.Int J Cardiovasc Imaging2013;29(7):1645-1653.
12 Brunner S,Todica A,B?ning G,et al.Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using[18 F]FDG-PET:comparison with cardiac MRI and monitoring erythropoietin therapy.Ejnmmi Res 2012;2(1):43-51.
13 Shen LJ,Lu S,Zhou YH,et al.Application of 18fluorodeoxyglucose fluorodeoxyglucose miniature positron emission tomography myocardial metabolic imaging in evaluating the rats model of dilated cardiomyopathy.Zhong Guo Xun Huan Za Zhi 2016;31(8):802-806.
14 Zhou YB,Zhang LL,Gao YJ,Zhou YB.Effects of Yiqi Yangyin,Huoxue Huayu decoction on cardiomyocyte apoptosis in experimental viral dilated cardiomyopathy mice.Zhong Xi Yi Jie He Xin Nao Xue Guan Bing Za Zhi2008;6(5):540-541.
15 Scaffidi P,Misteli T,Bianchi ME.Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.Nature2002;418(6894):191-195.
16 Vande Walle,Kanneganti TD,Lamkanfi M.HMGB1 release by inflammasomes.Virulence2011;2(2):162-165.
17 RoseNR.Myoearditis:infection versus autoimmunity.JClin Immunol 2009;29(6):730-737.
18 Eriksson U,Kurrer MO,Sehmitz N,et al.Interleukin-6-defieient mice resist development of autoimmune myoearditis assoeiated with impaired upregulation of complement C3.Circulation 2003;107(2):320-325.
19 Souza AW,Westra J,Limburg PC,Bijl M,Kallenberg CG.HMGB1 in vascular diseases:Its role in vascular inflammation and atherosclerosis.Autoimmun Rev 2012;11(12):909-917.
20 Volz HC,Laohachewin D,Schellberg D,et al.HMGB1is an independent predictor of death and heart transplantation in heart failure.Clin Res Cardiol 2012;101(6):427-435.
21 Tzeng HP,Fan J,Vallejo JG,et al.Negative inotropic effects of high-mobility group box 1 protein in isolated contracting cardiac myocytes.Am J Physiol Heart Circ Physiol 2008;294(3):H1490-H1496.
22 Wu H,Yang J,Ding JW,et al.Expression of high mobility group protein B,interleukin-6 and tumor necrosis factor in patients with dilated cardiomyopathy.Lin Chuang Xin Xue Guan Bing Za Zhi 2013;29(2):88-90.
23 T Ohtsuka,M Hamada,H Saeki,et al.Comparison of effects of carvedilol versus metoprolol on cytokine levels in patients with idiopathic dilated cardiomyopathy.Am JCardiol 2002;89(8):996-999.
24 Liu C,Song YM,Huang L,Li AM,Geng SH,Yu XJ.Effects of valsartan and perindopril on cytokines and myocardial fibrosis in patients with congestive heart failure.Di San Jun Yi Da Xue Xue Bao 2008;30(12):1189-1192.