米力农对糖尿病性心肌损伤大鼠心肌收缩力和氧供平衡的影响及其机制

目的探究米力农对糖尿病性心肌损伤大鼠心肌收缩力和氧供平衡的影响及其机制。方法将健康雄性Sprague-Dawley大鼠分为对照组(腹膜注射等量生理盐水)、心肌损伤模型组(注射STZ诱导大鼠糖尿病模型造成心肌损伤)和米力农给药组(模型组基础上腹膜注射0. 5μg/kg米力农治疗,共10周)。生理记录仪监测大鼠左室收缩压(LVSP),左室舒张末压(LVEDP)、最大左室升/降率(±dp/dtmax)及氧动力指标;RT-q PCR检测促炎因子Caspase-3、细胞色素C(Cyt C)、白细胞介素1β(1L-1β)的mRNA表达情况;蛋白印迹分析心肌损伤指标脑钠肽(BNP)、心钠肽(ANP)的蛋白表达;酶联免疫吸附(ELISA)实验检测三磷酸腺苷(ATP)、二磷酸腺苷(ADP)和一磷酸腺苷(AMP)。结果心肌损伤组较对照组LVSP、+dp/dtmax、-dp/dtmax降低、LVEDP升高(P <0. 05),米力农给药组较心肌损伤组LVSP、+dp/dtmax、-dp/dtmax升高、LVEDP降低(P <0. 05);心肌损伤组较对照组氧供给、氧消耗降低,氧摄取率升高(P <0. 05),米力农给药组较心肌损伤组氧供给、氧消耗升高,氧摄取率降低(P <0. 05);心肌损伤组较对照组Caspase-3、Cyt C、1L-1β的mRNA以及BNP、ANP蛋白表达均显著升高(P <0. 05),米力农给药组较心肌损伤组以上指标均显著降低(P <0. 05);心肌损伤组较对照组ATP/ADP和ATP/AMP降低,米力农给药组较心肌损伤组以上指标军显著升高(P <0. 05)。结论米力农可以改善大鼠糖尿病引起的心肌线粒体能量代谢异常及心肌收缩能力,增加组织氧供给,对缓解心肌损伤具有重要价值。

Mechanism of milrinone affecting myocardial contractility and oxygen supply balance in rats with diabetic myocardial injury

Objective To investigate the mechanism of milrinone affecting myocardial contractility and oxygen supply balance in rats with diabetic myocardial injury. Methods Healthy male Sprague-Dawley rats were divided into control group( equal amount of saline through the peritoneum injection),myocardial injury model group( injection of STZ-induced diabetic rat model of myocardial injury) and milrinone administration group( 0. 5 μg/kg of milinong treatment based on model group by peritoneal injection,10 weeks in total). The physiological recorder were used to monitor LVSP,LVEDP, ± dp/dtmax and oxygen dynamics in rats;RT-qPCR was used to detect the mRNA expression of pro-inflammatory factors caspase-3,Cyt C and 1 L-1β. Western blot analysis of protein expression of BNP and ANP in myocardial injury markers;ATP,ADP and AMP were detected by ELISA. Results Compared with the control group,LVSP, + dp/dtmax,-dp/dtmax and LVEDP were increased in the myocardial injury group( P < 0. 05),the LVSP, + dp/dtmax,-dp/dtmax and LVEDP were lower in the milrinone group than those in the myocardial injury group( P < 0. 05). Compared with the control group,the oxygen supply and oxygen consumption in the myocardial injury group decreased,and the oxygen uptake rate increased( P < 0. 05),and compared with the myocardial injury group,the milrinone administration group had higher oxygen supply and oxygen consumption,and the oxygen uptake rate decreased( P < 0. 05). Compared with the control group,the expressions of caspase-3,Cyt C,1 L-1β and BNP and ANP protein were significantly increased in the myocardial injury group,and compared with the myocardial injury group,the above indicators of the milrinone administration group were significantly lower( P < 0. 05). Compared with the control group,the ATP/ADP and ATP/AMP were decreased in the myocardial injury group,and the milrinone administration group was significantly higher than the myocardial injury group( P < 0. 05). Conclusion Milrinone can improve myocardial mitochondrial energy metabolism and myocardial contractility,increase tissue oxygen supply,and is of great value in relieving myocardial injury.