川芎嗪抑制ROCK的表达降低模拟失重大鼠血管Ca^(2+)敏感性

Tetramethylpyrazine suppresses enhanced Ca^(2+)sensitivity by inhibiting ROCK expression in rat arteries under simulated weightlessness

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。

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 rats 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.