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川芎嗪抑制ROCK的表达降低模拟失重大鼠血管Ca2＋敏感性
Tetramethylpyrazine suppresses enhanced Ca2+ sensitivity by inhibiting ROCK expression in rat arteries under simulated weightlessness
- 西北大学学报（自然科学版） 2024年54卷第5期 页码：919-928
- 作者机构：
1.西北大学 生命科学学院/西部资源生物与现代生物技术教育部重点实验室，陕西 西安 710069
2.西北工业大学 生命学院/西安市特种医学与健康工程重点实验室，陕西 西安 710072
- 作者简介：
王慧平，男，博士，硕士生导师，从事动物生理学研究，wanghp@nwu.edu.cn。
高云芳，女，博士，教授，博士生导师，从事动物生理学研究，gaoyunf@nwu.edu.cn。
- 基金信息：国家自然科学基金(32071517;32070442);西北大学大学生创新训练计划项目(2024)
DOI：10.16152/j.cnki.xdxbzr.2024-05-014
中图分类号： Q955纸质出版日期：2024-10-25，
收稿日期：2024-06-01，
- 稿件说明：
移动端阅览
王慧平, 白晓镯, 赵晶, 等. 川芎嗪抑制ROCK的表达降低模拟失重大鼠血管Ca2＋敏感性[J]. 西北大学学报（自然科学版）, 2024,54(5):919-928.
WANG Huiping, BAI Xiaozhuo, ZHAO Jing, et al. Tetramethylpyrazine suppresses enhanced Ca2+ sensitivity by inhibiting ROCK expression in rat arteries under simulated weightlessness[J]. Journal of Northwest University (Natural Science Edition), 2024,54(5):919-928.
王慧平, 白晓镯, 赵晶, 等. 川芎嗪抑制ROCK的表达降低模拟失重大鼠血管Ca2＋敏感性[J]. 西北大学学报（自然科学版）, 2024,54(5):919-928. DOI： 10.16152/j.cnki.xdxbzr.2024-05-014.
WANG Huiping, BAI Xiaozhuo, ZHAO Jing, et al. Tetramethylpyrazine suppresses enhanced Ca2+ sensitivity by inhibiting ROCK expression in rat arteries under simulated weightlessness[J]. Journal of Northwest University (Natural Science Edition), 2024,54(5):919-928. DOI： 10.16152/j.cnki.xdxbzr.2024-05-014.
摘要
研究失重条件下血管平滑肌收缩性、Ca
2＋
敏感性及其调控通路RhoA-ROCK蛋白表达的变化，以及川芎嗪干预对其的影响。大鼠尾部悬吊模拟失重，在机体前、后部分别选取颈总动脉和肠系膜上动脉。在模拟失重大鼠颈总动脉中，由苯肾上腺素（PHE）或KCl诱发的血管收缩性和Ca
2＋
敏感性增强，RhoA激酶2（ROCK II）的表达、肌球蛋白磷酸酶靶亚基1（MYPT1）和肌球蛋白调节轻链（MLC）的磷酸化水平均上升，血管孵育Y-27632（ROCK特异性抑制剂）后可降低以上变化。模拟失重大鼠灌饲川芎嗪亦可降低以上变化。模拟失重后，大鼠肠系膜上动脉的收缩性和Ca
2＋
敏感性、ROCK II的表达、MYPT1和MLC的磷酸化水平降低，血管孵育Y-27632对以上变化无明显作用。模拟失重大鼠灌饲川芎嗪亦对以上变化无明显作用。结果表明，由RhoA-ROCK调控的血管平滑肌Ca
2＋
敏感性的变化可能是失重条件下机体前后部血管收缩性发生区域性重塑的关键因素。川芎嗪可抑制ROCK蛋白的表达，降低血管平滑肌升高的Ca
2＋
敏感性，从而纠正失重条件下机体前部血管收缩性的增强，但对失重条件下机体后部血管收缩性的减弱无恢复作用。
Abstract
To detect the changes of vascular smooth muscle Ca
2+
sensitivity and the expression of its regulatory pathway RhoA-ROCK in different parts of the body under weightlessness
and the effect of tetramethylpyrazine on it. Tail-suspension was used to simulate weightlessness in rats
and the common carotid and superior mesenteric arteries were selected from the anterior and posterior body
respectively. In the common carotid artery of simulated weightlessness rats
the vasoconstriction induced by PHE and KCl was enhanced. The Ca
2+
sensitivity
the protein expression level of ROCK II
the phosphorylation level of MYPT1 and MLC
was increased. After incubating Y-27632 (Specific inhibitor of ROCK) with the common carotid artery of simulated weightlessness rats
the above enhanced changes could be reduced. Administration of tetramethylpyrazine to simulated weightlessness rats could also reduce the above enhanced changes. In the superior mesenteric artery of simulated weightlessness rats
the vasoconstriction
the Ca
2+
sensitivity
the protein expression level of ROCK II
the phosphorylation level of MYPT1 and MLC
was decreased. Incubating Y-27632 with the superior mesenteric artery of simulated weightlessness rats had no effect on the above weakened changes. Administration of tetramethylpyrazine to simulated weightlessness r
ats also had no effect on the above weakened changes. The results indicate that the distinct changes in Ca
2+
sensitivity regulated by RhoA-ROCK may be responsible for the different directional changes of vascular contraction function in the anterior and posterior body under weightlessness. Tetramethylpyrazine can inhibit the expression of ROCK to suppress the elevated vascular smooth muscle Ca
2+
sensitivity
thereby correct the enhanced vascular contraction function in the anterior part of the body under weightlessness
but has no improvement effect on the weakened vascular contraction function in the posterior part of the body under weightlessness.
关键词
Ca2＋敏感性RhoA-ROCK血管收缩性模拟失重川芎嗪
Keywords
Ca2+ sensitivityRhoA-ROCKvascular contraction functionsimulated weightlessnesstetramethylpyrazine
references
SHEN M, FRISHMAN W H. Effects of spaceflight on cardiovascular physiology and health [J]. Cardiology in Review, 2019, 27(3): 122-126.
DIEDRICH A, PARANJAPE S Y, ROBERTSON D. Plasma and blood volume in space [J]. American Journal of the Medical Sciences, 2007, 334(1): 80-85.
ZHANG L F. Vascular adaptation to microgravity: What have we learned? [J]. Journal of Applied Physiology, 2001, 91(6): 2415-2430.
ZHANG L F. Region-specific vascular remodeling and its prevention by artificial gravity in weightless environment [J]. European Journal of Applied Physiology, 2013, 113(12): 2873-2895.
WANG Z C, BAI Y G, YU J W, et al. Caveolae regulate vasoconstriction of conduit arteries to angiotensin II in hindlimb unweighted rats [J]. Journal of Physiology, 2015, 593(20): 4561-4574.
ZICHA J, BEHULIAK M, PINTEROVA M, et al. The interaction of calcium entry and calcium sensitization in the control of vascular tone and blood pressure of normotensive and hypertensive rats [J]. Physiological Research, 2014, 63(1): S19-S27.
CHUNG J H, BIESIADECKI B J, ZIOLO M T, et al. Myofilament calcium sensitivity: Role in regulation of in vivo cardiac contraction and relaxation [J]. Frontiers in Physiology, 2016, 7: 562.
REN X F, HENSLEY N, BRADY M B, et al. The genetic and molecular bases for hypertrophic cardiomyopathy: The role for calcium sensitization [J]. Journal of Cardiothoracic and Vascular Anesthesia, 2018, 32(1): 478-487.
YANG Q H, HORI M. Characterization of contractile machinery of vascular smooth muscles in hypertension [J]. Life-Basel, 2021, 11(7): 702.
YU Z B, ZHANG L F, JIN J P. A proteolytic NH2-terminal truncation of cardiac troponin I that is up-regulated in simulated microgravity [J]. Journal of Biological Chemistry, 2001, 276(19): 15753-15760.
ZHANG L, SONG Z, CHANG H, et al. Enhanced N-terminal degradation of troponin I blunts cardiac function responsiveness to isoproterenol in 4-week tail-suspended rats [J]. Molecular Medicine Reports, 2013, 7(1): 271-279.
UEDA K, AOYAMA Y, SASAKA-KITAMURA F, et al. Contractile responses of the basilar artery isolated from rabbits exposed to 8-day head-down tilt [J]. Japanese Journal of Physiology, 2001, 51(2): 209-215.
LOIRAND G, GUILLUY C, PACAUD P. Regulation of Rho proteins by phosphorylation in the cardiovascular system [J]. Trends in Cardiovascular Medicine, 2006, 16(6): 199-204.
ITO M, OKAMOTO R, ITO H, et al. Regulation of myosin light-chain phosphorylation and its roles in cardiovascular physiology and pathophysiology [J]. Hypertension Research, 2022, 45(1): 40-52.
QIAN W, XIONG X, FANG Z, et al. Protective effect of tetramethylpyrazine on myocardial ischemia-reperfusion injury [J]. Evidence-Based Complementary and Alternative Medicine, 2014(1): 107501.
YANG G, QIAN C, WANG N, et al. Tetramethylpyrazine protects against oxygen-glucose deprivation-induced brain microvascular endothelial cells injury via Rho/Rho-kinase signaling pathway [J]. Cellular and Molecular Neurobiology, 2017, 37(4): 619-633.
LI S Y, YANG Z, GAO Y F, et al. Ligustrazine and the contractile properties of soleus muscle in hindlimb-unloaded rats [J]. Aviation Space and Environmental Medicine, 2012, 83(11): 1049-1054.
ZHANG J, LI Y, LI G, et al. Identification of the optimal dose and calpain system regulation of tetramethylpyrazine on the prevention of skeletal muscle atrophy in hindlimb unloading rats [J]. Biomedicine & Pharmacotherapy, 2017, 96: 513-523.
GAO Y F, ARFAT Y, WANG H P, et al. Muscle atrophy induced by mechanical unloading: Mechanisms and potential countermeasures [J]. Frontiers in Physiology, 2018, 9: 235.
KIZUB I V, PAVLOVA O O, JOHNSON C D, et al. Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats [J]. British Journal of Pharmacology, 2010, 159(8): 1724-1731.
HU Y, LI T, TANG X F, et al. Effects of ischemic preconditioning on vascular reactivity and calcium sensitivity after hemorrhagic shock and their relationship to the RhoA-Rho-kinase pathway in rats [J]. Journal of Cardiovascular Pharmacology, 2011, 57(2): 231-239.
BEHULIAK M, BENCZE M, VANECKOVA I, et al. Basal and activated calcium sensitization mediated by RhoA/Rho kinase pathway in rats with genetic and salt hypertension [J]. Biomed Research International, 2017: 8029728.
SUMMERS S M, NGUYEN S V, PURDY R E. Hindlimb unweighting induces changes in the RhoA-Rho-kinase pathway of the rat abdominal aorta [J]. Vascular Pharmacology, 2008, 48(4/5/6): 208-214.
WANG Z C, LIU H, BAI Y G, et al. 28-Day hindlimb unweighting reduces expression of Rho kinase and inhibits its effects in femoral artery of rat [J]. Journal of Physiology and Biochemistry, 2015, 71(2): 205-216.
王忠超, 刘焕, 於进文, 等. 模拟失重大鼠胸主动脉收缩功能的变化可能与Rho激酶改变有关[J]. 心脏杂志, 2012, 24(6): 677-680.
WANG Z C, LIU H, YU J W, et al. Changed vasoconstriction of thoracic aorta induced by simulated microgravity in rats may be associated with altered Rho kinase[J]. Chinese Heart Journal, 2012, 24(6): 677-680.
WU Y, YUE Z J, WANG Q G, et al. BKCa compensates impaired coronary vasoreactivity through RhoA/ROCK pathway in hind-limb unweighted rats [J]. The FASEB Journal, 2019, 33(12): 13358-13366.
ZHAO S D, ZHANG Y, CHEN Q F, et al. A modified ”double-hit” induced acute lung injury model in rats and protective effects of tetramethylpyrazine on the injury via Rho/ROCK pathway [J]. International Journal of Clinical and Experimental Pathology, 2015, 8(5): 4581-4587.
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