Tác dụng bảo vệ của lycopene đối với chức năng tim và xơ hóa cơ tim sau nhồi máu cơ tim cấp tính ở chuột theo cơ chế điều chỉnh p38 và MMP-9

Journal of Molecular Histology - Tập 45 - Trang 113-120 - 2013
Xin Wang1,2, Hong Lv1,2, Yongwei Gu1,2, Xi Wang1,2, Hong Cao1,2, Yanhong Tang1,2, Hui Chen1,2, Congxin Huang1,2
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuchang, Wuhan, People’s Republic of China
2Cardiovascular Research Institute, Wuhan University, Wuhan, People’s Republic of China

Tóm tắt

Ma trận ngoại bào (ECM) đóng vai trò quan trọng trong việc duy trì hình dạng và chức năng của thất trái, và việc ức chế tái cấu trúc ECM có những lợi ích điều trị giúp giảm tiến triển của tái cấu trúc thất. Các nghiên cứu gần đây cho thấy lycopene có tác dụng bảo vệ tim. Trong nghiên cứu này, một mô hình nhồi máu cơ tim (MI) ở chuột đã được thiết lập bằng cách thắt động mạch vành bên trái xuống. Sau phẫu thuật, chuột được điều trị bằng lycopene hoặc dung dịch muối sinh lý. Sau 28 ngày, các chuột được thực hiện siêu âm tim và sau đó bị hy sinh. Xơ hóa cơ tim được quan sát bằng phương pháp nhuộm Masson. Sự biểu hiện protein collagen loại I, MMP-9 và MAPK được phát hiện ở vùng thiếu máu xung quanh khu vực MI bằng phương pháp western blot. Điều trị bằng lycopene đã tăng tỷ số phân suất tống máu (EF) từ 45.2 ± 3.12 % lên 51.1 ± 4.63, đồng thời giảm LVEDd từ 6.52 ± 0.37 mm xuống 6.18 ± 0.41 mm và LVESd từ 4.29 ± 0.63 xuống 3.94 ± 0.37 sau 28 ngày nhồi máu cơ tim. Lycopene làm giảm sự gia tăng biểu hiện MMP-9 và collagen loại I do MI gây ra, đồng thời ức chế sự kích hoạt p38. Hơn nữa, lycopene đã làm giảm thể tích collagen trong vùng quanh nhồi máu. Dữ liệu cho thấy lycopene cải thiện chức năng tim và tái cấu trúc thất bằng cách ức chế sự kích hoạt p38 và biểu hiện MMP-9.

Từ khóa

#lycopene #nhồi máu cơ tim #chức năng tim #xơ hóa cơ tim #MMP-9 #p38

Tài liệu tham khảo

Anversa P, Olivetti G, Capasso JM (1991) Cellular basis of ventricular remodeling after myocardial infarction. Am J Cardiol 68:7D–16D Biddle M, Moser D, Song EK et al (2012) Higher dietary lycopene intake is associated with longer cardiac event-free survival in patients with heart failure. Eur J Cardiovasc Nurs 12:377–384 Boyle AJ, Kelly DJ, Zhang Y et al (2005) Inhibition of protein kinase C reduces left ventricular fibrosis and dysfunction following myocardial infarction. J Mol Cell Cardiol 39:213–221 Chole RH, Gondivkar SM, Gadbail AR et al (2012) Review of drug treatment of oral submucous fibrosis. Oral Oncol 48:393–398 Clinton SK (1998) Lycopene: chemistry, biology, and implications for human health and disease. Nutr Rev 56:35–51 Deng W, Jiang D, Fang Y et al (2013) Hesperetin protects against cardiac remodelling induced by pressure overload in mice. J Mol Histol 44:575–585 Ducharme A, Frantz S, Aikawa M et al (2000) Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest 106:55–62 Garcia RA, Brown KL, Pavelec RS et al (2005) Abnormal cardiac wall motion and early matrix metalloproteinase activity. Am J Physiol Heart Circ Physiol 288:H1080–H1087 Gu Y, Wang X, Wu G et al (2012) Artemisinin suppresses sympathetic hyperinnervation following myocardial infarction via anti-inflammatory effects. J Mol Histol 43:737–743 Heymans S, Luttun A, Nuyens D et al (1999) Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med 5:1135–1142 Jugdutt BI, Joljart MJ, Khan MI (1996) Rate of collagen deposition during healing and ventricular remodeling after myocardial infarction in rat and dog models. Circulation 94:94–101 Karppi J, Kurl S, Nurmi T et al (2009) Serum lycopene and the risk of cancer: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study. Ann Epidemiol 19:512–518 Kawaguchi M, Techigawara M, Ishihata T (1997) A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension. Heart Vessels 12:267–274 Kelly D, Cockerill G, Ng LL et al (2007) Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study. Eur Heart J 28:711–718 Kim JY, Paik JK, Kim OY et al (2011) Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men. Atherosclerosis 215:189–195 Kitade Y, Watanabe S, Masaki T et al (2002) Inhibition of liver fibrosis in LEC rats by a carotenoid, lycopene, or a herbal medicine, Sho-saiko-to. Hepatol Res 22:196–205 Lo HM, Hung CF, Tseng YL et al (2007) Lycopene binds PDGF-BB and inhibits PDGF-BB-induced intracellular signaling transduction pathway in rat smooth muscle cells. Biochem Pharmacol 74:54–63 Martos R, Baugh J, Ledwidge M et al (2007) Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation 115:888–895 McEneny J, Wade L, Young IS et al (2013) Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals. J Nutr Biochem 24:163–168 Murray AJ, Cole MA, Lygate CA et al (2008) Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart. J Mol Cell Cardiol 44:694–700 Nunoda S, Genda A, Sugihara N et al (1985) Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus. Heart Vessels 1:43–47 Palozza P, Simone RE, Catalano A et al (2012) Modulation of MMP-9 pathway by lycopene in macrophages and fibroblasts exposed to cigarette smoke. Inflamm Allergy Drug Targets 11:36–47 Pan Z, Zhao W, Zhang X et al (2011) Scutellarin alleviates interstitial fibrosis and cardiac dysfunction of infarct rats by inhibiting TGFbeta1 expression and activation of p38-MAPK and ERK1/2. Br J Pharmacol 162:688–700 Parvin R, Akhter N (2008) Protective effect of tomato against adrenaline-induced myocardial infarction in rats. Bangladesh Med Res Counc Bull 34:104–108 Pauschinger M, Knopf D, Petschauer S et al (1999) Dilated cardiomyopathy is associated with significant changes in collagen type I/III ratio. Circulation 99:2750–2756 Pennathur S, Maitra D, Byun J et al (2010) Potent antioxidative activity of lycopene: a potential role in scavenging hypochlorous acid. Free Radic Biol Med 49:205–213 Qiu X, Yuan Y, Vaishnav A et al (2013) Effects of lycopene on protein expression in human primary prostatic epithelial cells. Cancer Prev Res (Phila) 6:419–427 Ren J, Zhang S, Kovacs A et al (2005) Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction. J Mol Cell Cardiol 38:617–623 Riccioni G, Mancini B, Di Ilio E et al (2008) Protective effect of lycopene in cardiovascular disease. Eur Rev Med Pharmacol Sci 12:183–190 Rissanen T, Voutilainen S, Nyyssonen K et al (2000) Low plasma lycopene concentration is associated with increased intima-media thickness of the carotid artery wall. Arterioscler Thromb Vasc Biol 20:2677–2681 See F, Thomas W, Way K et al (2004) p38 mitogen-activated protein kinase inhibition improves cardiac function and attenuates left ventricular remodeling following myocardial infarction in the rat. J Am Coll Cardiol 44:1679–1689 Spallarossa P, Altieri P, Garibaldi S et al (2006) Matrix metalloproteinase-2 and -9 are induced differently by doxorubicin in H9c2 cells: the role of MAP kinases and NAD(P)H oxidase. Cardiovasc Res 69:736–745 Spinale FG, Escobar GP, Hendrick JW et al (2006) Chronic matrix metalloproteinase inhibition following myocardial infarction in mice: differential effects on short and long-term survival. J Pharmacol Exp Ther 318:966–973 Weber KT (1989) Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol 13:1637–1652 Weber KT, Sun Y, Tyagi SC et al (1994) Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. J Mol Cell Cardiol 26:279–292 Xaplanteris P, Vlachopoulos C, Pietri P et al (2012) Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects. Nutr Res 32:390–394 Yoshiyama M, Omura T, Takeuchi K et al (2001) Angiotensin blockade inhibits increased JNKs, AP-1 and NF- kappa B DNA-binding activities in myocardial infarcted rats. J Mol Cell Cardiol 33:799–810 Zhou C, Han W, Zhang P et al (2008) Lycopene from tomatoes partially alleviates the bleomycin-induced experimental pulmonary fibrosis in rats. Nutr Res 28:122–130 Zhou H, Yang HX, Yuan Y et al (2013) Paeoniflorin attenuates pressure overload-induced cardiac remodeling via inhibition of TGFbeta/Smads and NF-kappaB pathways. J Mol Histol 44:357–367