[Effects of fasudil on isoproterenol induced cardiac hypertrophy in rats].

OBJECTIVE

To investigate the effects and mechanisms of fasudil (Fas) on cardiac hypertrophy (CH) induced by isoprenaline(Iso) in rats.

METHODS

Except for the normal control group, the rest three groups rats were injected subcutaneously with Iso(5mg/kg) for setting up CH model. SD rats were randomly divided into four groups:Normal control group, Iso model group, Fas with low-dose group (5 mg/kg, i.p) and Fas with high-dose group (20 mg/kg, i.p). Animals were treated with Fas for 8 weeks. After the treatment, the following index were detected:heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), left ventricular systolic maximum rate (+dp/dt) and left ventricular diastolic maximum rate (-dp/dt). The body weight(BW) and heart weight (HW) were weighed and heart weight index (HWI) was calculateed. Myocardial tissue specimens, HE and Masson staining were performed for observing the histopathological changes. The protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2) in myocardial tissue was determined by using immunohistochemical methods. The expression of ERK1/2 mRNA in the myocardial tissue was detected by using semi-quantitative RT-PCR method.

RESULTS

Compared with normal control group, HR and LVEDP wereincreased significantly, while LVSP and ±dp/dtmax were decreased significantly; HWI was increased significantly in CH group; The myocardial cell volume and the cell gap were increased,cells arranged disorder, and severe myocardial interstitial fibrosis was presented in CH group. The expression of ERK1/2 mRNA was significantly increased. After Fas treatment, the systolic and diastolic functions of heart were improved, cell volume was reduced, cell gap became small, cells arranged in neat rows, and the fibrosis was significantly reduced. The expressions of RhoA, ERK1/2 mRNA were significantly reduced. The damages of myocardial tissue were improved in different degrees.

CONCLUSIONS

ERK1/2 signaling pathway is involved in Iso induced CH. Fas protects against the CH of rats induced by Iso, which mechanisms may be related with blocking ERK1/2 signaling pathway.