Effect of atorvastatin on myocardial fibrosis induced by aldosterone
- VernacularTitle:阿托伐他汀对实验性大鼠心肌纤维化的干预作用及可能机制
- Author:
Lifeng HE
;
Likun MA
- Publication Type:Journal Article
- Keywords:
Atorvastatin;
Aldosterone;
Myocardial fibrosis
- From:
Chinese Journal of Pathophysiology
2010;26(2):227-232
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effects and mechanisms of atorvastatin on myocardial fibrosis induced by aldosterone in SD rats. METHODS: Forty male uninephrectomized SD rats were limited to drink 1% NaCl water for 4 weeks and assigned to the follow groups: vehicle control rats (CON group);aldosterone treated rats (ALD group);spironolactone + aldosterone treated rats(SPI+ALD group);atorvastatin + aldosterone treated rats (ATO+ALD group). Blood pressure was measured by catheterization. Expression of platelet-derived growth factor (PDGF-A, PDGF-B), platelet-derived growth factor receptor (PDGFR-α, PDGFR-β) and ectodermal dysplasia-1 (ED-1) were analyzed by immunohistochemistry. Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were analyzed by Sirius-Red staining. Myocardium osteopontin protein was detected by Western blotting analysis. RESULTS: Mean arterial blood pressure in ALD group, SPI+ALD group and ATO+ALD group was elevated, and significant difference was observed between the three groups and vehicle control group (P<0.01 or P<0.05). Myocardial fibrosis was observed in ALD group. Compared to other three groups, the index of CVF and PVCA was increased significantly (P<0.01 or P<0.05). No significant difference of the index of CVF and PVCA between ATO+ALD group and SPI+ALD group was observed (P>0.05). Compared to other groups, the levels of PDGF-A, PDGF-B, PDGFR-α, ED-1 and OPN in ALD group were significantly increased (P<0.01 or P<0.05). The levels of PDGF-A, PDGF-B, PDGFR-α and OPN were no significant difference between ATO+ALD group and SPI+ALD group (P<0.01 or P<0.05). However, the level of ED-1 in ATO+ALD group was significantly decreased compared to SPI+ALD group (P<0.05). No significant difference of PDGFR-β level among four groups was found (P>0.05). CONCLUSION: These results suggest that atorvastatin may attenuate myocardial fibrosis induced by aldosterone. The mechanisms concern with reduction of macrophage infiltration, expression of inflammatory cytokines OPN, partially inhibition of platelet-derived growth factor and its receptor expression.