镁离子在高磷诱导慢性肾衰竭大鼠胸主动脉血管钙化中的作用及机制研究

Effect of Magnesium Ions on Phosphorus- induced Thoracic Aortic Calcification in Chronic Renal Failure Rats and Its Mechanism

目的探讨镁离子在高磷诱导慢性肾衰竭大鼠模型血管钙化中的作用及其机制。方法将32只雄性SD大鼠采用随机数字表法均分为对照组(A组)、慢性肾衰竭血管钙化组(B1组)、低镁组(B2组)、高镁组(B3组)。用硫酸腺嘌呤加高磷饮食复制慢性肾衰竭大鼠血管钙化模型。造模成功后测量4组大鼠主动脉脉搏波速率(PWV),反转录聚合酶链反应(RT-PCR)方法检测主动脉血管钙化标志分子核心结合因子α1(Cbfα1)mRNA的表达情况,von Kossa染色及邻甲酚酞络合酮比色法测定钙水平。结果 B1组血肌酐、尿素氮、血磷水平高于A组(t=32.284、22.010、26.000,P<0.05)。4组血镁水平比较,差异有统计学意义(F=7.745,P<0.05);B3组血镁水平高于B2组(q=2.897,P<0.05)。4组主动脉钙水平比较,差异有统计学意义(F=6.824,P<0.05);B2组主动脉钙水平高于B1组(q=13.192,P<0.05);B1组主动脉钙水平高于A组(q=21.925,P<0.05);B3组主动脉钙水平低于B1组和B2组(q=9.333、21.782,P<0.05)。4组胸主动脉PWV值比较,差异有统计学意义(F=6.454,P<0.05);B2组PWV值高于B1组(q=13.492,P<0.05);B1组PWV值高于A组(q=14.311,P<0.05);B3组PWV值低于B1组和B2组(q=5.333、16.865,P<0.05)。4组胸主动脉Cbfα1 mRNA表达量比较,差异有统计学意义(F=3.212,P<0.05);B1和B2组Cbfα1 mRNA表达量高于A组(q=7.333、13.565,P<0.05);B3组Cbfα1mRNA表达量低于B1组和B2组(q=10.198、13.858,P<0.05);B2组Cbfα1 mRNA表达量高于B1组(q=12.279,P<0.05)。结论镁离子能够抑制高磷诱导的慢性肾衰竭大鼠血管钙化,改善血管弹性功能;其可能机制之一是镁离子通过抑制高磷诱导血管平滑肌细胞表型转化实现。

Objective To investigate the effect of magnesium ions on phosphorus- induced thoracic calcification in chronic renal failure rats and its mechanism. Methods 32 male SD rats were divided into four groups by random number table method： normal control group（ A group）,chronic kidney failure complicated with vascular calcification group（ B1 group）,low magnesium group（ B2 group） and high magnesium group（ B3 group）,8 in each group. The rat models of chronic kidney failure complicated with vascular calcification were established by adenine sulphate and high phosphorus diets. The aortic pulse wave velocity（ PWV） was measured after the rat model was established,the expression of core binding factor alphα1（ Cbfα1）mRNA were determined by RT- PCR. The calcium levels of aorta were determined by von Kossa staining and cresolphthalein o-complexone colorimetry. Results The serum levels of creatinine,urea nitrogen and phosphorus among rats in B1 group were significantly higher than those in A group（ t = 32. 284,22. 010,26. 000,P〈0. 05）. There were significant differences in serum magnesium level among four groups（ F = 7. 745,P〈0. 05）. The serum magnesium levels among rats in B3 group were significantly higher than those in B2 group（ q = 2. 897,P〈0. 05）. There were significant differences in aortic calcium level among four groups（ F = 6. 824,P〈0. 05）. The aortic calcium levels among rats in B2 group were significantly higher than those in B1group（ q = 13. 192,P〈0. 05）. The aortic calcium levels among rats in B1 group were significantly higher than those in A group（ q = 21. 925,P〈0. 05）. The aortic calcium levels among rats in B3 group were significantly lower than those in B1 and B2 groups,respectively（ q = 9. 333,21. 782,P〈0. 05）. There were significant differences in thoracic aortic PWV value among four groups（ F = 6. 454,P〈0. 05）. The aortic PWV values among rats in B2 group were significantly higher than those in B1group（ q = 13. 492,P〈0. 05）. The aortic PWV values among rats in B1 group were significantly higher than those in A group（ q = 14. 311,P〈0. 05）. The aortic PWV values among rats in B3 group were significantly lower than those in B1 group and B2 group,respectively（ q = 5. 333,16. 865,P〈0. 05）. There were significant differences in aortic calcium Cbfα1 m RNA expression level among four groups（ F = 3. 212,P〈0. 05）. The Cbfα1 mRNA expression levels in B1 group and B2 group were significantly higher than those in A group,respectively（ q = 7. 333,13. 565,P〈0. 05）. The Cbfα1 mRNA expression levels in B3 group were significantly lower than those in B1 group and B2 group,respectively（ q = 10. 198,13. 858,P〈0. 05）. The Cbfα1 mRNA expression levels in B2 group were significantly higher than those in B1 group（ q = 12. 279,P〈0. 05）. Conclusion Magnesium iron can inhibit thoracic calcification in rats with phosphorus- induced chronic renal failure,thus improve vessel elastic function. Magnesium ions can inhibit the phosphorus- induced phenotypic transformation of VSMCs,which is maybe one of the possible mechanisms.