|
|
|
| Research on the effects of ligustrazine phosphate on angiotensin Ⅱ induced hypertrophy of H9c2 cells and its mechanism |
| LI Chunhong WANG Jie WU Aiming CHEN Huiyang ZHANG Ting MA Zhe GAO Yonghong LOU Lixia▲ |
| Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China |
|
|
|
Abstract Objective To investigate the effects of ligustrazine phosphate (ligu) on hypertrophy of H9c2 cells induced by angiotensin Ⅱ (Ang Ⅱ) and its possible mechanism. Methods H9c2 cells hypertrophy induced by Ang Ⅱ was used as a model. The cells were randomly divided into control group, model group, ligustrazine phosphate group, ligustrazine phosphate + NE-100 group and NE-100 group. Rhodamine-Phalloidin staining was used to observe the changes of cell area; Fura-2 AM was used to determine the changes of intracellular Ca2+ concentration; Western blot was used to detect the expression of Sigma-1 receptor (Sig-1R), calcineurin (CaN) and inositol 1, 4, 5-trisphosphate receptor (IP3R). Results Ligustrazine phosphate could inhibit the increase of cell area induced by Ang Ⅱ (P ＜ 0.05), which could be blocked by NE-100, a Sig-1R inhibitor (P ＜ 0.05), and Ligustrazine phosphate could inhibit the increase of BNP mRNA level induced by Ang Ⅱ (P ＜ 0.05). Ang Ⅱ incubation decreased the expression level of Sig-1R protein (P ＜ 0.05), ligustrazine phosphate had a tendency to restore the expression level of Sig-1R protein (P ＞ 0.05); ligustrazine phosphate intervention could significantly reduce the increase of IP3R protein level induced by Ang II (P ＜ 0.05), NE-100 blocked the effect (P ＜ 0.05); but ligustrazine phosphate intervention had no effect on the increase of CaN induced by Ang Ⅱ (P ＞ 0.05). In addition, ligustrazine phosphate inhibited the increase of intracellular Ca2+ in H9c2 cells induced by Ang Ⅱ, which was blocked by NE-100 (P ＜ 0.05). Conclusion Ligustrazine phosphate inhibits cardiomyocyte hypertrophy by interfering with the expression of IP3R through Sig-1R and affecting intracellular calcium balance.
|
|
|
|
|
|
[1] 金雪娟，周京敏，葛均波.心力衰竭流行病学的研究进展[J].中国临床医学，2013，20（6）：852-855.
[2] 黄峻.中国心力衰竭流行病学特点和防治策略[J].中华心脏与心律电子杂志，2015，3（2）：2-3.
[3] 邱伯雍，王永霞.慢性心力衰竭流行病学及防治研究进展[J].中华实用诊断与治疗杂志，2017，31（6）：619-621.
[4] Gardin JM，Lauer MS. Left ventricular hypertrophy：the next treatable，silent killer？[J]. JAMA，2004，292（19）：2396-2398.
[5] Frey N，Katus HA，Olson EN，et al. Hypertrophy of the heart： a new therapeutic target？[J]. Circulation，2004，109（13）：1580-1589.
[6] 陈可冀，吴宗贵，朱明军，等.慢性心力衰竭中西医结合诊疗专家共识[J].心脑血管病防治，2016，16（5）：340-347.
[7] 罗伟华.川芎嗪的临床应用及其制剂研究进展[J].中国现代药物应用，2017，11（18）：191-193.
[8] 于妍，王硕仁，孙逸坤，等.川芎嗪在逆转心肌细胞肥大过程中对心肌细胞线粒体结构和功能的影响[J].中国中西医结合杂志，2012，32（5）：661-665.
[9] 杨爽，杨凯，陆莹，等.川芎嗪对血管紧张素Ⅱ诱导心肌细胞肥大的影响[J].中国动脉硬化杂志，2010，18（5）：355-357.
[10] Su TC，Lin SH，Lee PT，et al. The sigma-1 receptor-zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury [J]. Neuropharmacology，2016， 105：1-9.
[11] Hayashi T，Rizzuto R，Hajnoczky G，et al. MAM：more than just a housekeeper [J]. Trends Cell Biol，2009，19（2）：81-88.
[12] Bhuiyan MS，Tagashira H，Shioda N，et al. Targeting sigma-1 receptor with fluvoxamine ameliorates pressure-overload-induced hypertrophy and dysfunctions [J]. Expert Opin Ther Targets，2010，14（10）：1009-1022.
[13] Ela C，Barg J，Vogel Z，et al. Sigma receptor ligands modulate contractility，Ca++ influx and beating rate in cultured cardiac myocytes [J]. J Pharmacol Exp Ther，1994， 269（3）：1300-1309.
[14] Tagashira H，Bhuiyan S，Shioda N，et al. Sigma1-receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice [J]. Am J Physiol Heart Circ Physiol，2010，299（5）：H1535-H1545.
[15] Houser SR，Molkentin JD. Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes？[J]. Sci Signal，2008，1（25）：pe31.
[16] Tsai SY，Hayashi T，Mori T，et al. Sigma-1 receptor chaperones and diseases [J]. Cent Nerv Syst Agents Med Chem，2009，9（3）：184-189.
[17] Tagashira H，Bhuiyan MS，Shioda N，et al. Fluvoxamine rescues mitochondrial Ca2+ transport and ATP production through sigma（1）-receptor in hypertrophic cardiomyocytes [J]. Life Sci，2014，95（2）：89-100.
[18] Hayashi T，Su TP. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival [J]. Cell，2007，131（3）：596-610.
[19] Urani A，Romieu P，Portales-Casamar E，et al. The antidepressant-like effect induced by the sigma（1）（sigma（1）） receptor agonist igmesine involves modulation of intracellular calcium mobilization [J]. Psychopharmacology（Berl），2002，163（1）：26-35.
[20] Chen W，An P，Quan XJ，et al. Ca（2+）/calmodulin-dependent protein kinase Ⅱ regulates colon cancer proliferation and migration via ERK1/2 and p38 pathways [J]. World J Gastroenterol，2017，23（33）：6111-6118.
[21] Tagashira H，Bhuiyan MS，Fukunaga K. Diverse regulation of IP3 and ryanodine receptors by pentazocine through sigma1-receptor in cardiomyocytes [J]. Am J Physiol Heart Circ Physiol，2013，305（8）：H1201-H1212.
[22] Go LO，Moschella MC，Watras J，et al. Differential regulation of two types of intracellular calcium release channels during end-stage heart failure [J]. J Clin Invest，1995， 95（2）：888-894.
[23] Nakayama H，Bodi I，Maillet M，et al. The IP3 receptor regulates cardiac hypertrophy in response to select stimuli [J]. Circ Res，2010，107（5）：659-666.
[24] 王婕，吴爱明，李春红，等.益气活血方对大鼠心肌梗死边缘区Sigma-1R、SERCA2a、IP3R mRNA表达的影响[J].中西医结合心脑血管病杂志，2018，16（9）：1180-1184. |
|
|
|
