阿托伐他汀与自发性高血压大鼠心肌细胞凋亡的关系研究

Effects of Atorvastatin on Myocardiocyte Apoptosis Spontaneously Hypertensive Rats

目的通过观察阿托伐他汀对自发性高血压大鼠（spontaneously hypertensive rats，SHR）心肌细胞凋亡的影响，初步探讨高血压心室重塑的可能机制。方法20只雄性SHR随机分为阿托伐他汀干预组（ATV组）和生理盐水组（NS组），以10只正常血压雄性WKY大鼠作为正常对照组（WKY组）分别给予阿托伐他汀和生理盐水灌胃，10周后进行心肌细胞凋亡等指标的测定。结果NS组大鼠和ATV组大鼠与WKY组大鼠相比，左室心肌细胞凋亡指数、血清及左室心肌中TNF-α蛋白、AngⅡ蛋白和血清中ET-1蛋白表达明显升高（P〈0．05），eNOS活性显著降低（P〈0．05），而ATV组大鼠与NS组大鼠比较，eNOS活性ATV组大鼠显著高于NS组大鼠（P〈0．05），余各指标均显著低于NS组大鼠（P〈0．05）。结论阿托伐他汀抑制高血压大鼠心肌细胞凋亡，减轻心室重塑和改善心功能可能与其抑制TNF-α、AngⅡ、ET-1的表达，提高eNOS活性有关。

Objective we aim at studying the mechanisms of atorvastatin to retard myocardiocyte apoptosis and improve left ventricular function in SHR. Methods Twenty healthy male SHR were randomly divided into atovastatin treatedment group （ ATV group） and 0.9% NaCl diet control group（ NS group）. At the same time, ten WKY rats to SHR, were used as normal control group （WKY group）. Rats in ATV group were treated with atorvastatin for 10 weeks, and rats in NS group and WKY group were treated with only 0.9% NaCl of the same volume in the same time. Treatment ten weeks later, myocardiocyte apoptosis indexes were examined. Results Compared with WKY group, the left ventricular myocardiocyte apoptosis index, the TNF - α, Ang Ⅱ , and ET - 1 concentration in the serum and expression in the left ventricular myocardia of ATV group and NS group significantly increased （ P 〈 0.05 ）, these indexes in the ATV group significantly decreased （ P 〈 0.05 ） compared with NS group, while the activity of eNOS significantly decreased （ P 〈 0.05 ）, the index in the ATV group significantly increased （ P 〈 0.05 ） compared with NS group. Conclusions Atorvastatin inhibits myocardium apoptosis, retards cardiac remodeling and improves left ven- tricular function of SHR, which may he related to these effects that it can decrease the expression of TNF - α, Ang Ⅱ and ET - 1 , and increase the activity of eNOS.