The effects and mechanism of ginsenoside Rg1 on myocardial remodeling in an animal model of chronic thromboembolic pulmonary hypertension

European Journal of Medical Research

Dao-xin Wang²  Yu-kun Zhang²  Jia Deng²  Xiu-qing Liao¹  Wang Deng²  Chang-yi Li² 

[1] Department of Respiratory Medicine, Chongqing Fuling Central Hospital, Fuling, Chongqing 408000, China;Department of Respiratory Medicine, the Second Affiliated Hospital of Chong Qing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 40010, China

关键词: Matrix metalloproteinases;    Myocardial remodeling;    Chronicthromboembolic pulmonary hypertension;    Ginsenoside Rg1;    Panax notoginseng saponins;   

Others  :  820097
DOI  :  10.1186/2047-783X-18-16

 received in 2013-01-15, accepted in 2013-05-17,  发布年份 2013

【 摘 要 】

Background

Recent studies haveshown that ginsenoside Rg1, extracted from the dry roots of Panax notoginseng as a traditional Asian medicine, plays an anti-fibrosis role in myocardial remodeling. However, the mechanism still remains unclear. In the present study, we investigate the effect of ginsenoside Rg1on the collagenic remodeling of myocardium in chronic thromboembolic pulmonary hypertension (CTEPH), and its potential mechanism.

Methods

A rat model of CTEPH was established by injecting thrombi through the jugular vein wice in2 weeks. Four weeks later, four groups (Group A: normal rats + normal saline; Group B: normal rats + Rg1; Group C: CTEPH model + normal saline; Group D: CTEPH model + Rg1) were established. Normal saline and Rg1 were administrated by intraperitoneal injection. Ineach group, we measured the hemodynamic parameters, as well as the right ventricle to left ventricle (RV/LV) thickness ratio. Myocardial tissue sections of the RV were stained by hematoxylin-eosin +gentian violet and the morphological characteristics were observed by light microscopy. The matrix metalloproteinases (MMP) -2 and −9 were detected by the western blot.

Results

Compared with Group A and Group B, the right ventricular systolic pressure was significantly increased in Group C and significantly decreased in Group D. Compared with Group A and Group B, the RV/LV thickness ratio of the rats was significantly higher in Group C and Group D. There was significant fibrosis with collagen in Group C compared with Group A and Group B, and less significant changes in Group D were observed compared with those in Group C. The expression of MMP-2 and MMP-9 exhibited a significant decrease in Group C and was also significantly decreased in Group D compared withGroup A and Group B. Also, a negative linear relationship was shown between collagen-I and the expression of MMP-2 and MMP-9.

Conclusions

Our animal study showed that ginsenoside Rg1 positively affects myocardial remodeling and pulmonary hemodynamics in CTEPH. Upregulation of the expression of MMP-2 and MMP-9 could explain the beneficial effects of ginsenoside Rg1 in CTEPH.

【 授权许可】

   
2013 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Xu DQ, Luo Y, Liu Y, Wang J, Zhang B, Xu M: Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats. Respir Res 2010, 24:182-187.
• [2]Peled N, Shitrit D, Fox BD, Shlomi D, Amital A, Bendayan D: Peripheral arterial stiffness and endothelial dysfunction in idiopathic and scleroderma associated pulmonary arterial hypertension. J Rheumatol 2009, 36:970-975.
• [3]Spinale FG: Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 2007, 87:1285-1342.
• [4]Ng TB: Pharmacological activity of sanchi ginseng (Panax notoginseng). J Pharm Pharmacol 2006, 58:1007-1019.
• [5]Li L, Sheng YX, Zhang JL, Wang SS, Guo DA: High performance liquid chromatographic assay for the active saponins from Panax notoginseng in rat tissues. Biomed Chromatogr 2006, 20:327-335.
• [6]Sun HX, Pan HJ, Pan YJ: Haemolytic activity and immunological adjuvant effect of Panax notoginseng saponins. Acta Pharmaceutica Sinica 2003, 24:1150-1154.
• [7]Chen SW, Li XH, Ye KH, Jiang ZF, Ren XD: Total saponins of Panax notoginseng protect rabbit iliac artery against balloon endothelial denudation injury. Acta Pharmaceutica Sinica 2004, 25:1151-1156.
• [8]Wang CZ, McEntee E, Wicks S, Wu JA, Yuan CS: Phytochemical and analytical studies of Panax notoginseng (Burk.). J Nat Med 2006, 60:97-106.
• [9]Nah SY, Park HJ, McClesky EW: A trace component of ginseng that inhibit Ca2+ channels through a pertussis toxin-sensitive G protein. Proc Natl Acad Sci USA 1995, 92:8739-8743.
• [10]Xu QH, Fang XL, Chen DF: Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. J Ethnopharmacol 2003, 84:187-192.
• [11]Wu L, Zhang W, Tang YH, Li H, Chen BY, Zhang GM: Effect of total saponins of ‘Panax notoginseng root’ on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in rats. Phytomedicine 2010, 17:233-240.
• [12]Wei HJ, Yang HH, Chen CH, Lin WW, Chen SC, Lai PH: Gelatin microspheres encapsulated with a nonpeptide angiogenic agent, ginsenoside Rg1, for intramyocardial injection in a rat model with infarcted myocardium. J Control Rel 2007, 120:27-34.
• [13]Wu F, Zhang SS, Kang GF: Effects of Panax notoginseng saponins on the expression of tumor necrosis factor alpha and secretion phospholipase A2 in rats with liver fibrosis. Zhong hua Gan Zang Bing Za Zhi 2003, 11:51-52. (in Chinese)
• [14]Moser KM, Cantor JP, Olman M, Villespin I, Graif JL, Konopka R: Chronic pulmonary thromboembolism in dogs treated with tranexamic acid. Circulation 1991, 83:1371-1379.
• [15]Borg TK, Caulfield JB: The collagen matrix of the heart. Fed Proc 1981, 40:2037-2041.
• [16]Shamhart PE, Meszaros JG: Non-fibrillar collagens: key mediators of post-infarction cardiac remodeling. Mol Cell Cardiol 2010, 48:530-537.
• [17]van den Borne SW, Diez J, Blankesteijn WM, Verjans J, Hofstra L, Narula J: Myocardial remodeling afterinfarction: the role of myofibroblasts. Nat Rev Cardiol 2010, 7:30-37.
• [18]Meybohm P, Gruenewald M, Albrecht M, Zacharowski KD, Lucius R, Zitta K, Koch A, Tran N, Scholz J, Bein B: Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling. PLoS One 2009, 4:e7588.
• [19]Yokota T, Osanai T, Hanada K, Kushibiki M, Abe N, Oikawa K: Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction: comparison with enalapril. Hear Vessel 2010, 25:460-468.
• [20]Adamcová M, Potáčová A, Popelová O, Stěrba M, Mazurová Y, Aupperle H: Cardiac remodeling and MMPs on the model of chronic daunorubicin-induced cardiomyopathy in rabbits. Physiol Res 2010, 59:831-836.
• [21]Nie R, Xie S, Du B, Liu X, Deng B, Wang J: Extracellular matrix metalloproteinase inducer (EMMPRIN) is increased in human left ventricle after acute myocardial infarction. Arch Med Res 2009, 40:605-611.
• [22]Bruggink AH, van Oosterhout MF, de Jonge N, Ivangh B, van Kuik J, Voorbij RH: Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern. J Heart Lung Transplant 2006, 25:1091-1098.