异莲心碱防止高血压大鼠左室肥厚的可能机制

Effects of Isoliensinine on Left Ventricular Hypertrophy and Its Possible Mechnism

背景既往报告异莲心碱是从莲子心中分离的一种双苄基喹啉生物碱单体,具有抗心律失常、Ca^(2+)拮抗及阻断α受体作用,对高血压左室肥厚有不同程度的改善。高血压左室肥厚心肌肌浆网钙泵(SERCA)活力较正常心肌降低。目的探讨异莲心碱对高血压大鼠左室肥厚及SERCA活力的影响。方法将二肾一夹肾血管性高血压大鼠(RHR)模型,随机分为3组:正常对照组、肾血管性高血压大鼠对照组(未治疗RHR组)和异莲心碱治疗组。在异莲心碱治疗组持续给药10周后,分别测定各组大鼠的血压、左室质量/体质量,以及左室心肌SERCA活力。结果治疗后,异莲心碱治疗组血压(136.4±14.6)mm Hg较未治疗RHR组(189.8±4.4)mm Hg显著降低(P<0.01);异莲心碱治疗组左室质量/体质量(2.23±0.43)也较未治疗RHR组(2.93±0.52)显著降低(P<0.05);异莲心碱治疗组左室心肌SERCA活力[(0.91±0.18)μmol/(g protein·min)]较未治疗RHR组[(0.61±0.23)μmol/(g protein·min)]显著升高(P<0.05),但仍较正常对照组[(1.32±0.18)μmol/(g protein·min)]低(P<0.01)。结论异莲心碱能降低RHR的血压,减低RHR的左室质量/体质量,对高血压左室肥厚具有一定的防治作用;其机制可能与异莲心碱能升高RHR肥厚心肌肌浆网SERCA活力,改善心肌细胞内钙超载有关。

Background Isoliensinine（IL） is a kind monomer alkaloid of double benzyl group quinoline separated from Plumula nelumbinis, which has been speculated to have antiarrhythmic effect, Ca^2＋ and αl-receptor blockade, and reversal the left ventricular hypertrophy （LVH）. It has been reported the activity of Sarco/Endoplasmic reticulum Ca^2＋-ATPase （SERCA） in essential hypertention （EH）/LVH patients was lower than that of healthy people. Objective To investigate the effects of Isoliensinine on left ventricular hypertrophy and activity of SERCA in 2 kidney 1 clamp （2K1C） hypertensive rats. Methods 2K1C hypertensive rats were randomly received Isoliensinine （RHR-IL, 5 mg/kg per day p. o, n= 16） or placebo. Blood pressure, left ventricle mass index（LVMI） and the activity of myocardial SERCA were measured after 10 weeks treatment. Six untreated SD rats were served as control. Results Isoliensinine decreased BP and LV/BM ratio （IL：136.4±14.6 vs control： 189.8±4.4 mm Hg, P〈0.01 ; IL：2.23±0. 43 vs control：2. 93±0.52, P〈0.05）, associated with increases in activity of myocardial SERCA [IL： 0. 91±0. 18 μmol/（g protein · min） vs control： 0.61 ± 0.23 μmol/（g protein · min）, P〈0.05], which was still lower than that of SD control rats [1.32±0.18 μmol/（g protein · min）, P〈0.01]. Conclusion Isoliensinine reduced blood pressure and LV/BM ratio and concurrently enhanced myocardial SERCA activity in renovascular hypertensive rats.