辛伐他汀对血管升压素诱导鼠心脏成纤维细胞增殖和胶原合成的影响

    Effects of Simvastatin on proliferation and collagen synthesis of rat cardiac fibroblasts induced by arginine vasopressin

    • 摘要: 目的 探讨辛伐他汀(Simvastatin,Sim)对血管升压素(AVP)诱导的新生SD大鼠心脏成纤维细胞(CF)增殖和胶原合成作用的影响,为防治高血压左室肥厚提供理论依据。方法 以培养的新生SD大鼠CF为实验模型,采用胰酶消化、差速贴壁法培养CF,运用MTT比色法和3H脯氨酸掺入法分别观察不同浓度Sim对AVP诱导CF增殖和胶原合成的作用及甲羟戊酸(mevalonate,MVA)干预的影响。结果 ①CF的3H脯氨酸掺入率随着Sim干预浓度的增加而降低,其中1 μmol/L和10 μmol/L Sim组的3H脯氨酸掺入率分别为(3.67±0.39)mBq/cell和(2.35±0.36)mBq/cell,明显低于对照组(5.01±0.58)mBq/cell(P<0.01);②MTT比色法A490值随Sim浓度的增加而降低,其中1 μmol/L和10 μmol/L Sim组的A490值分别为0.221±0.038和0.163±0.021,均较对照组A490值(0.395±0.039)显著降低(P<0.01);③10 μmol/L Sim+1 mmol/L MVA组的3H脯氨酸掺入率和MTT比色法A490值分别为(5.38±0.72)mBq/cell和0.419±0.051,均显著高于同组10 μmol/L Sim(P<0.01)。结论 Sim抑制AVP诱导的CF增殖和胶原合成,其机制可能通过MVA代谢途径实现。

       

      Abstract: AIM To investigate the effects of simvastatin (Sim) on the proliferation and collagen synthesis of rat cardiac fibroblasts (CF) induced by arginine vasopressin (AVP). METHODS CFs of neonatal SpragueDawley (SD) rats were isolated by trypsin digestion method and the growtHarrested CFs were stimulated with 0.1 μmol/L AVP in the presence of varying concentrations of Sim (0.01 μmol/L-10 μmol/L) and MVA (1 μmol/L-1 mmol/L). Collagen synthesis was measured by3Hproline incorporation and the cell number was evaluated by MTT. RESULTS The results showed that: ①Sim decreased3Hproline incorporation in CFs in a concentrationdependent manner.3Hproline incorporation values of 1 μmol/L Sim 3Hproline group and 10 μmol/L Sim group (3.67±0.39 mBq/cell and 2.35±0.36 mBq/cell, respectively) were significantly lower than that of the control (5.01±0.58 mBq/cell,P<0.01). ②The absorbance A490 values by MTT assay decreased with the elevation of Sim concentration. The A490 values of 1 μmol/L Sim group and 10 μmol/L Sim group (0.221±0.038, 0.163±0.021, respectively) were significantly lower than that of the control (0.395±0.039,P<0.01). ③3Hproline incorporation in CFs and the A490 value of 10 μmol/L Sim+1 mmol/L MVA group (5.38±0.72 mBq/cell and 0.419±0.051, respectively) were significantly higher compared with those of 10 μmol/L Sim group (P<0.01). CONCLUSION The results indicate that Sim decreases CF number and collagen synthesis induce by AVP and that MVA pathway may play an important role in the CF proliferation and collagen synthesis.

       

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