异丙酚静脉注射对老年患者左心室功能及心肌β肾上腺素受体的影响

Effect of intravenous propofol injection on left ventricular function and myocardial betadrenoreceptor in elderly patients

目的探究异丙酚静脉注射对老年患者左心室功能及心肌β肾上腺素受体的影响。方法2017年6月至2018年12月在中山市中医院筛选65-75岁的二尖瓣置换患者46例作为研究对象。试验分为对照组与异丙酚组:异泊酚组患者使用微泵注射异泊酚[2-6 mg/(kg·h)]+静脉注射右美托咪定0.7μg/kg,脑电双频指数监测(BIS)值保持在40-60间;对照组患者注射等量0.9%氯化钠溶液+静脉注射右美托咪定0.7μg/kg。分别记录给药前与给药后10、20、30 min时各试验组患者的心率、左心室收缩压(left ventricular systolic pressure,LVSP)及左心室内压变化最大速率(±dp/dtmax);利用苏木素伊红(HE)染色结合光学显微镜对心肌组织形态进行观察;通过反转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)试验对心肌组织中β1、β2、β3受体mRNA表达量进行测定;通过Western blot试验对心肌组织中钙调神经磷酸酶(calcineurin,CaN)、活化T细胞核因子3(nuclear factor of activated T-cells 3,NFAT3)、锌指转录因子(zinc finger transcription factor gata 4,GATA4)蛋白的表达量进行测定。结果对照组患者手术前后心率比较,差异无统计学意义(P>0.05)。异泊酚组患者静脉注射异泊酚后心率比对照组低,差异有统计学意义(P<0.05)。对照组患者手术前后LVSP比较,差异无统计学意义(P>0.05)。异泊酚组患者静脉注射异泊酚后,在给药的30 min内,LVSP降低,差异有统计学意义(P<0.05)。对照组手术前后左心室内压变化率比较,差异无统计学意义(P>0.05)。异泊酚组患者静脉注射异泊酚后,左心室内压变化率降低,差异有统计学意义(P<0.05)。对照组患者的心肌纤维排列整齐,有明确的水平线;异泊酚组患者心肌纤维无序,横向面肌肌丝大小不同,有些心肌细胞肥大,细胞质液泡变性,尤其在细胞核周围,肌丝粒化或网状化,间质扩大。与对照组患者相比,异丙酚组患者β1受体mRNA表达减少、β3受体mRNA表达增加,差异有统计学意义(P<0.05);β2受体mRNA表达差异无统计学意义(P>0.05)。与对照组患者比较,异丙酚组患者的NFAT3、GATA表达量增加,差异有统计学意义(P<0.05)。与对照组患者比较,异丙酚组患者的CaN、GATA 4磷酸化水平增加,NFAT3磷酸化水平降低,差异有统计学意义(P<0.05)。结论异丙酚静脉注射降低老年患者左心室功能,降低β1受体mRNA的表达,促进β3受体mRNA表达,对β2受体mRNA表达无显著影响。

Objectives To investigate the effects of intravenous propofol injection on left ventricular function and myo⁃cardial betadrenoreceptor in elderly patients.Methods Totally 46 patients aged 65 to 75 years were screened for mitral valve replacement from June 2017 to December 2018 in Zhongshan Hospital of Traditional Chinese Medicine.The experiment was divided into normal control group and propofol group.Heart rate,left ventricular systolic pressure(LVSP)and maximum rate of left ventricular pressure(±dp/dtmax)were recorded before and after administration for 10,20,and 30 minutes respectively.The morphology of myocardial tissue was observed by hematoxylin eosin(HE)staining and microscope.The mRNA expression levels ofβ1,β2 andβ3 receptors in myocardial tissues were deter⁃mined by reverse transcription polymerase chain reaction(RT-PCR).The expressions of calcineurin(CaN),nuclear factor of activated T-cells 3(NFAT3)and zinc finger transcription factor gata 4(GATA 4)proteins in myocardial tissue were measured by Western blot.Results There was no significant change in heart rate before and after operation in normal control group(P>0.05).Heart rate of propofol group after intravenous propofol injection was significantly lower than that of normal control group(P<0.05).There was no significant change in LVSP before and after operation in normal control group(P>0.05).LVSP significantly reduced with 30 min after intravenous propofol injection in patients of propofol group(P<0.05).There was no significant change in left indoor pressure rate before and after operation in normal control group(P>0.05).Left indoor pressure rate significantly reduced after intravenous propofol injection in patients of propofol group(P<0.05).The results of HE staining showed that the myocardial fibers in normal control group were neatly arranged with clear horizontal lines.While the myocardial fibers in propofol group were disordered,and the size of transverse facial muscle myofilaments was different.Some myocardial cells were hypertrophy and cytoplasmic vacuole degeneration,especially around the nucleus,myofiluminescence or reticulation,and interstitium enlargement.RT-PCR results showed that,compared with normal control group,propofol group had a reducing expression ofβ1 receptor mRNA(P<0.05),no statistical significance of the expression ofβ2 receptor mRNA(P>0.05),and a significant increasing in the expression ofβ3 receptor mRNA.Western blot results showed that the expressions of NFAT3 and GATA in propofol group significantly increased compared with those in normal control group(P<0.05),and the phosphorylation levels of CaN and GATA4 increased compared with those in normal control group(P<0.05),and the phosphorylation level of NFAT3 reduced compared with that in normal control group(P<0.05).Conclusions Intravenous propofol injection reduces left ventricular function in elderly patients,decreases the expression ofβ1 receptor mRNA,promotes the expres⁃sion ofβ3 receptor mRNA,and has no significant effect on the expression ofβ2 receptor mRNA.