卡维地洛与缬沙坦对自发性高血压大鼠心肌细胞凋亡的影响

Effects of Carvedilol, Valsartan and Their Combination on Cardiomyocyte Apoptosis in Spontaneously Hypertensive rats

目的: 探讨卡维地洛(Carvedilol,Car)、缬沙坦(Valsatan,Val)及其合用对自发性高血压大鼠(SHR)心肌细胞凋亡及血浆血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、超氧化物歧化酶(superoxidedismutase,SOD)、丙二醛(malondialdehyde,MDA)的影响。方法: 6周龄雄性SHR24只,随机分为对照组,其他3组为干预组,即Car组,Val组及Car1-SVal合用组,后3组用药8周后,腹腔麻醉取下腔静脉血3ml,测AngⅡ、SOD与MDA;开胸取左心室游离壁心肌,采用TUNEL法检测心肌细胞凋亡率(cardiacmyocyteapoptosisrate,CMAR)。结果: 与对照组比较,各干预组CMAR及血浆MDA明显降低,而血浆SOD明显增高,Car组及合用组血浆AngⅡ明显降低,而Val组明显增高(P<0 01);与Car组、Val组比较,合用组CMAR及血浆MDA明显降低,血浆SOD明显增高,而血浆AngⅡ明显高于Car组,低于Val组(P<0 01)。Val组与Car组比较,CMAR无显著性差异(P>0 05),而血浆SOD明显降低,血浆MDA、AngⅡ明显升高(P<0 01);各组中血浆MDA与CMAR均呈正相关,而血浆SOD与其呈负相关;Val组血浆AngⅡ与CMAR呈负相关,其余各组呈正相关(P<0 05)。结论: Car,Val可抑制SHR心肌细胞凋亡,二者合用效应更明显,可能与两药影响血浆AngⅡ、SOD、MDA含量有关。

Objective: To explore the effects of carvedilol (Car), valsartan (Val) and their combination on cardiomyocyte apoptosis, and on contents of superoxide dismutase (SOD), malondialdehyde (MDA) and plasma angiotensinⅡ(AngⅡ) in spontaneously hypertensive rats (SHR). Methods: 24 male 6-week-old SHRs were randomly divided into four groups (n=6 for each). One group served as control while the other as treatment groups which were respectively given Car 20mg·kg -1 .d -1 , Val 40 mg·kg -1 .d -1 and Car 20mg·kg -1 .d -1 +Val 40 mg·kg -1 .d -1 (dissolved in NS 5ml) by stomach filling for 8 weeks. Rats in control group were given NS instead. 3ml of blood from each rat was collected from inferior vena cava after rats being anesthetized with pentobarbital (40mg·kg -1 , ip), to measure the contents of SOD,MDA and AngⅡ in plasma. Free wall of left ventricle was cut for pathological examination and the cardiomyocyte apoptosis rate (CMAR) was detected with TUNEL method. Results: Compared with the control, CMAR and MDA significantly decreased, and SOD significantly increased in treated groups. However, Ang II significantly decreased in Car and Car+Val groups, and increased in Val group (P<0.01). Comparing with Car and Val groups, CMAR and MDA significantly decreased, and SOD significantly increased in Car+Val group. In Car+Val group, Ang II was significantly higher than that in Car group and lower than that in Val group (P<0.01). No significant difference was found between the CMAR of Car and Val groups (P>0.05). SOD content was significantly lower and plasma AngII and MDA contents were significantly higher in Val group than in Car group (P<0.01). CMAR was positively correlated with MDA, and negatively correlated with SOD in all the groups. But, it had a negative correlation with AngII in Val group, and a positive correlation with AngII in other groups (P<0.05). Conclusions: carvedilol and valsartan could obviously inhibit the cardiomyocyte apoptosis, and their combination is more efficient. The mechanism might be the influence of the two drugs on the contents of AngⅡ, SOD and MDA in plasma.