Simvastatin prevents hypertrophy and keeps cardiac function in myocardium of rabbit with overlord by promoting PPAR gamma and inhibiting NF-kappa B
- VernacularTitle:辛伐他汀对慢性心力衰竭兔心肌PPARγ mRNA、蛋白表达及核因子κB表达、活性的影响
- Author:
Hongtao QI
;
Zhihua LIU
;
Bin JIANG
;
Cao ZOU
;
Caiming ZHAO
;
Hongxia LI
;
Lianhua HAN
;
Tingbo JIANG
;
Jianping SONG
;
Wenping JIANG
- Publication Type:Journal Article
- Keywords:
simvastatin;
rabbit;
congestive heart failure;
hypertrophy;
PPAR gamma;
NF-κB
- From:
Chinese Pharmacological Bulletin
2010;26(1):115-120
- CountryChina
- Language:Chinese
-
Abstract:
Aim To observe the effects of simvastatin on PPARγ and p65 subunit of NF-κB and to invest the mechanism of simvastatin preventing hypertrophy and keeping cardiac function.Methods 24 rabbits were divided into 4 groups.Rabbits received sham operation as health control in group I. In other groups, aortic regurgitation and coarctation of ascending aorta were operated in rabbits.Rabbits received no drugs in Group Ⅱ. In group Ⅲ, rabbits were given simvastatin 5 mg·kg~(-1)·d~(-1) after the operation for 8 weeks. In group Ⅳ, rabbits were given simvastatin 5 mg·kg~(-1)·d~(-1) after 4 weeks of operation for 4 weeks. At the beginning and the end of the experiment, left ventricular end diastolic pressure (LVEDP) was measured with catheter. At the end of the experiment, heart weight (HW), left ventricular weight (LVW), body weight (BW), heart weight/body weight radio (HW/BW radio), left ventricular weight/body weight radio (LVW/BW radio) were measured.The PPARγ mRNA expression was analyzed by RT-PCR. PPARγ and p65 protein expression in cardiomyocyte nuclear were analyzed through Western blot. The activity of p65 was analyzed with EMSA.Results The HW, LVW, HW/BW were significantly decreased in the early and late treatment group than in CHF group(P<0.05,P<0.01). The LVW/BW was significantly decreased inearly treatment group than in CHF group, too (P<0.01). The LVEDP was significantly decreased in the early and late treatment group than in CHF group (P<0.01). The mRNA and protein of PPARγ significantly fell in CHF heart (P<0.01). The activity and protein expression of p65 were significantly increased in CHF heart (P<0.01). Simvastatin increased the mRNA and protein expression of PPARγ and decreased the activity and protein expression of p65 (P<0.01).Conclusions Simvastatin inhibits the cardiac hypertrophy and improves cardiac function. The mechanism of simvastatin on cardiac remodeling and function relates to the increase of PPARγ expression and preventing the NF-κB activation.
