山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (2): 1-6.doi: 10.6040/j.issn.1671-7554.0.2019.1047
• 基础医学 • 下一篇
赵位昆1,吕祥威2,武琦3,鲁攀1,彭丽1,覃秋语1
ZHAO Weikun1, LYU Xiangwei2, WU Qi3, LU Pan1, PENG Li1, QIN Qiuyu1
摘要: 目的 探讨6-姜酚(6-G)对血管紧张素Ⅱ(AngⅡ)诱导大鼠心房纤维化的作用及机制。 方法 8周龄雄性SD大鼠18只,按照随机数字表法分为假手术组、模型组和6-G干预+AngⅡ组,每组6只。假手术组经尾静脉注射0.9%氯化钠注射液,2 mg/kg;模型组经尾静脉注射AngⅡ,2 mg/kg,制备心房纤维化模型;6-G干预+AngⅡ组经尾静脉注射6-G,6 mg/kg,30 min后再经尾静脉注射AngⅡ,2 mg/kg。3组持续给药14 d,1次/d。各组经超声心动图检测大鼠心功能,采用ELISA法检测心肌损伤标记物的变化,采用Masson三色染色法检测大鼠心房纤维化程度,采用Western blotting法检测大鼠心房转化生长因子-β1(TGF-β1)、Ⅰ型胶原(Collagen-Ⅰ)的表达。 结果 假手术组、模型组和6-G干预+AngⅡ组3组之间相比,左心室射血分数(LVEF)(F=1.500,P=0.255)、左心室缩短率(LVFS)(F=0.793,P=0.471)、左室收缩末期内径(LVESD)(F=0.104,P=0.902)、左室舒张末期内径(LVEDd)(P=0.566)和CK-MB(F=0.089,P=0.915)、cTnT(F=0.181,P=0.836)差异无统计学意义(P>0.05)。与假手术组相比,模型组和6-G干预+AngⅡ组心房纤维化程度增加,胶原分数(F=322.527)、TGF-β1(F=44.537)、Collagen-Ⅰ(F=45.626)表达均升高,3组之间差异有统计学意义(P<0.05)。与假手术组相比,模型组大鼠上述心功能和心肌损伤标志物无明显差异(P>0.017),心房纤维化程度增加,胶原分数、TGF-β1、Collagen-Ⅰ表达均升高,差异有统计学意义(P<0.017)。与模型组相比,6-G干预+AngⅡ组大鼠上述心功能和心肌损伤标志物差异无统计学意义(P>0.017),心房纤维化程度减轻,胶原分数、TGF-β1、Collagen-Ⅰ表达均降低,差异有统计学意义(P<0.017)。 结论 6-G可减轻AngⅡ诱导的大鼠心房纤维化,其机制可能与抑制TGF-β1的表达,减少Collagen-Ⅰ的生成有关。
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[1] | Dilaveris P, Antoniou CK, Manolakou P, et al. Biomarkers associated with atrial fibrosis and remodeling [J]. Curr Med Chem, 2019, 26(5): 780-802. |
[2] | Yang PS, Lee SH, Park J, et al. Atrial tissue expression of receptor for advanced glycation end-products(RAGE)and atrial fibrosis in patients with mitral valve disease [J]. Int J Cardiol, 2016, 220: 1-6. doi: 10.1016/j.ijcard.2016.06.137. |
[3] | Brown NJ. Mineralocorticoid receptor activation and atrial fibrosis [J]. Hypertension, 2019, 73(2): 294-295. |
[4] | Liu Y, Niu XH, Yin X, et al. Elevated circulating fibrocytes is a marker of left atrial fibrosis and recurrence of persistent atrial fibrillation [J]. J Am Heart Assoc, 2018, 7(6): e008083. |
[5] | Dudley SC Jr, Hoch NE, McCann LA, et al. Atrial fibrillation increases production of superoxide by the left atrium and left atrial appendage: role of the NADPH and xanthine oxidases [J]. Circulation, 2005, 112(9): 1266-1273. |
[6] | Fan J, Zou L, Cui K, et al. Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling [J]. Basic Res Cardiol, 2015, 110(4): 45. |
[7] | Hirsh BJ, Copeland-Halperin RS, Halperin JL. Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism: mechanistic links and clinical inferences [J]. J Am Coll Cardiol, 2015, 65(20): 2239-2251. |
[8] | 吴英智, 傅强, 严全能, 等. 姜酚在心血管疾病中的药理作用研究进展[J].中国临床药理学杂志, 2017, 33(18): 1824-1827. WU Yingzhi, FU Qiang, YAN Quanneng, et al. Research progress on pharmacological actions of gingerols in cardiovasular disease [J]. The Chinese Journal of Clinical Pharmacology, 2017, 33(18): 1824-1827. |
[9] | Kamato D, Babaahmadi Rezaei H, Getachew R, et al.(S)- |
[6] | -Gingerol inhibits TGF-β-stimulated biglycan synthesis but not glycosaminoglycan hyperelongation in human vascular smooth muscle cells [J]. J Pharm Pharmacol, 2013, 65(7): 1026-1036. |
[10] | Liu Q, Liu J, Guo H, et al. 6-Gingerol: A novel AT1 antagonist for the treatment of cardiovascular disease [J]. Planta Med, 2013, 79(5): 322-326. |
[11] | Xu T, Qin G, Jiang W, et al. 6-Gingerol protects heart by suppressing myocardial ischemia/reperfusion induced inflammation via the PI3K/Akt-dependent mechanism in rats [J]. Evid Based Complement Alternat Med, 2018, 2018: 1-9. doi: 10. 1155/2018/6209679. |
[12] | 吕祥威, 徐彤彤. 6-姜酚抑制氧化应激减轻大鼠心肌缺血/再灌注损伤[J]. 临床心血管病杂志, 2017, 33(6): 575-579. LV Xiangwei, XU Tongtong. 6-Gingerol inhibits oxidative stress ameliorated myocardial ischemia/reperfusion injury in rats [J]. Journal of Clinical Cardiology, 2017, 33(6): 575-579. |
[13] | Lv X, Xu T, Wu Q, et al. 6-Gingerol activates PI3K/Akt and inhibits apoptosis to attenuate myocardial ischemia/reperfusion injury [J]. Evid Based Complement Alternat Med, 2018, 2018: 1-9. doi: 10. 1155/2018/9024034. |
[14] | Fukui A, Takahashi N, Nakada C, et al. Role of leptin signaling in the pathogenesis of angiotensin II-mediated atrial fibrosis and fibrillation [J]. Circ Arrhythm Electrophysiol, 2013, 6(2): 402-409. |
[15] | Wang R, Yi X, Li X, et al. Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease [J]. Int J Clin Exp Pathol, 2015, 8(11): 14901-14908. |
[16] | Corradi D. Atrial fibrillation from the pathologists perspective [J]. Cardiovasc Pathol, 2014, 23(2): 71-84. |
[17] | Dzeshka MS, Lip GY, Snezhitskiy V, et al. Cardiac fibrosis in patients with atrial fibrillation: mechanisms and clinical implications [J]. J Am Coll Cardiol, 2015, 66(8): 943-959. |
[18] | 方曙, 钟国强, 蒋智渊, 等. 转化生长因子-βⅢ型受体在心房颤动心肌纤维化表达[J]. 临床心血管病杂志, 2016, 32(6): 555-558. FANG Shu, ZHONG Guoqiang, JIANG Zhiyuan, et al. Expression of transforming growth factor beta type Ⅲ receptor in human atrial myocardium of atrial fibrillation patient[J]. Journal of Clinical Cardiology, 2016, 32(6): 555-558. |
[19] | Chen XQ, Liu X, Wang QX, et al. Pioglitazone inhibits angiotensin II-induced atrial fibroblasts proliferation via NF-κB/TGF-β1/TRIF/TRAF6 pathway [J]. Exp Cell Res, 2015, 330(1): 43-55. |
[20] | Tian Y, Wang Y, Chen W, et al. Role of serum TGF-β1 level in atrial fibrosis and outcome after catheter ablation for paroxysmal atrial fibrillation [J]. Medicine(Baltimore), 2017, 96(51): e9210. |
[21] | Polejaeva IA, Ranjan R, Davies CJ, et al. Increased susceptibility to atrial fibrillation secondary to atrial fibrosis in transgenic goats expressing transforming growth factor-β1 [J]. J Cardiovasc Electrophysiol, 2016, 27(10): 1220-1229. |
[22] | Kupfahl C, Pink D, Friedrich K, et al. Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen mRNA expression in the human heart [J]. Cardiovasc Res, 2000, 46(3): 463-475. |
[23] | Zhang L, Zhang N, Tang X, et al. Increased α-actinin-2 expression in the atrial myocardium of patients with atrial fibrillation related to rheumatic heart disease[J]. Cardiology, 2016, 135(3): 151-159. |
[24] | 刘发金, 肖骅, 唐雪娇, 等. 转化生长因子-β1对大鼠心房、心室成纤维细胞胶原表达的影响[J]. 解放军医学杂志, 2015, 40(7): 540-546. LIU Fajin, XIAO Hua, TANG Xuejiao, et al. Effect of TGF-β1 on the expression of collagen in rat atrial and ventricular fibroblasts [J]. Medical Journal of Chinese People's Liberation Army, 2015, 40(7): 540-546. |
[25] | Park SA, Park IH, Cho JS, et al. Effect of |
[6] | -gingerol on myofibroblast differentiation in transforming growth factor beta 1-induced nasal polyp-derived fibroblasts [J]. Am J Rhinol Allergy, 2012, 26(2): 97-103. |
[26] | Hong Y, Cao H, Wang Q, et al. MiR-22 may suppress fibrogenesis by targeting TGFβR I in Cardiac Fibroblasts [J]. Cell Physiol Biochem, 2016, 40(6): 1345-1353. |
[27] | Wang K, Lu D, Zhang B, et al. Renal denervation attenuates multi organ fibrosis and improves vascular remodeling in rats with transverse aortic constriction induced cardiomyopathy [J]. Cell Physiol Biochem, 2016, 40(3-4): 465-476. |
[28] | Aguilar H, Fricovsky E, Ihm S, et al. Role for high-glucose-induced protein O-GLcNAcylation in stimulating cardiac fibrolast collagen synthesis [J]. Am J Physiol Cell Physiol, 2014, 306(9): 794-804. |
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