Inhabition Of Matrine On The AngⅡ-induced Proliferation Of Cardiac Fibroblasts And Its Mechanism

AIM: To study the influnence of matrine(Mat) on the preliferation of cultured neonatal rat cardiac fibroblasts(CFs) induced by Angiotensin II ,and to investigate its mechanism.METHODS: The neonatal rat cardiac fibroblasts were extracted by enzymatic digestion and anchorage velocity-dependent separation method. CFs were divided into six groups:control group, Ang II group ,Losartan group, different concentration Mat (0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L )+ Ang II group. After a 24-hour treatment, the cells of each group were collected and the flowing measures were carried out. CFs proliferation was measured by thiazolyl blue(MTT) assay; the expression of CyclinD1 of CFs was detected by immunocytochemical staining; the expression of p27 was detected by immunofluorescence staining;Cell cyclin distribution and p21, p27 CyclinDi expression were determined by flow cytometre.RESULTS: 1.Compared with control group, MTT value of CFs was increased in Ang II group. The percentage of CFs in S stage was upregulated and the percentage of cells in G0/G1 stage was significant downregulated by Ang II . Ang II could decreased the expression of p27,but it had no effect on the expressions of p21 and CyclinDi (both P>0.05). These effects of the Ang II on the CFs were completely inhabited by the losartan, an AT] receptor antagonist. 2. Compared with Ang II group, MTT values of CFs in Mat + Ang II treatment groups were decreased. The percentage of S stage cells was downregulated and the percentage of G0/G1 stage cells was upregulated by a simultaneous treatment with Mat Ang II.. Furthermore, coinstantaneous treatment of CFs with Mat and Ang II was associated with elevation of p27 and p21. These effects of Mat on the angiotensin II-induced cardiac fibroblasts growth were in a concentration dependent manner.CONCLUSIONS: 1 .Ang II-stimulated CFs proliferation was mediated by activation of AT1 receptors. A corresponding decrease in the expression of p27 in CFs may be related to this proliferaing effect, which has no relation with the expression of p21 and CyclinD1. 2.Mat could effectively inhibit the prolifertion of CFs induced by AngII by upregulatingp27 and p21 expression in a concentration dependent manner, which may play a important role in the regression of heart remodeling.