小檗碱降低通过阻止P38通路活化在PMA诱导的巨噬细胞中下调MMP- 9和EMMPRIN的表达

Int J Cardiol 2011 Jan;146(2):153-8.  [IF:6.802]

Berberine reduces both MMP-9 and EMMPRIN expression through prevention of p38 pathway activation in PMA-induced macrophages.

Huang Z , Wang L , Meng S , Wang Y , Chen T , Wang C .

Department of Cardiology, XinHua Hospital, Shanghai Jiaotong University Medical School, 1665 Kongjiang Road, Shanghai, 200092, PR China. susiehzq@yahoo.cn

上海交通大学医学院，新华医院心内科

Abstract

Overproduction of MMPs (matrix metalloproteinases) and EMMPRIN (extracellular matrix metalloproteinase inducer) by monocytes/macrophages leads to atherosclerotic plaque rupture by degrading the extracellular matrix. Serum MMP-9 levels may therefore represent a novel marker of inflammation in patients with known coronary artery disease. The purpose of our study was to determine if berberine, a natural extract from Rhizoma coptidis, had any effect on the expression of MMP-9 and EMMPRIN in PMA-induced macrophages. Human monocytic THP-1 cells were pretreated with berberine for 1 h, and then induced by PMA for 48 h. Total RNA and protein were collected for Real-time PCR and Western blot analysis, respectively. Culture supernatants were collected to determine MMP-9 activity. In the present study, we demonstrated that berberine inhibited the expression of MMP-9 and EMMPRIN at both the mRNA and protein levels in a dose-dependent manner in PMA-induced macrophages, and that it also reduced MMP-9 activity. Furthermore, berberine also suppressed p38 signaling pathway activation in PMA-induced macrophages. The data indicate that berberine reduces MMP-9 and EMMPRIN expression by suppressing the activation of p38 pathway in PMA-induced macrophages. This suggests a potential role for berberine as a therapeutic aid for stabilizing atherosclerotic plaque.