Effects of Selective Estrogen Receptor Modulator Raloxifene Plus 17-beta Estradiol in Aorta and Mammary Gland of Female Experimental Atherosclerosis Rabbits and Possible Involvement of ERK Signal Tran

Qiu-Ling Xiang ； Yu Chen ； Gui-Ping Lin ； Zhi Tan ； Ting-Huai Wang

《The Chinese Journal of Physiology》 49卷3期 (2006/06) Pp. 132-140

並列摘要

The present study investigated the effects of raloxifene, a second generation selective estrogen receptor modulator (SERM), plus 17-βE2 on aortic atherosclerosis and mammary gland hyperplasia in ovariectomized, cholesterol-fed rabbits. Following 10 weeks of raloxifene, 17-βE2, or raloxifene plus 17βE2 administration, serum total cholesterol, triglyceride, low density lipoprotein were significantly decreased in the drug groups compared to the placebo group. Consistent with serum lipid results, the total lesion area for each aorta of the drug groups decreased significantly as compared to the placebo group. HE staining of aorta paraffin section showed that in the drug groups the endothelial monolayer was almost continuous. While in mammary gland, HE staining of paraffin sections indicated the hyperplasia of epithelial cells (in 17-βE2 group) was obviously inhibited in raloxifene plus 17-βE2 group. In cultured vascular smooth muscle cell (VSMC), the results of MTT and [3H] TdR incorporation showed that the drug groups could inhibit AngⅡ-induced proliferation of VSMC. Western blotting proved that raloxifene plus 17-βE2 inhibited the expression of phosphorylated ERK protein, similar to 17-βE2 but different from raloxifene. This effect was inhibited by PD98059 (inhibitor of MAPK) or ICI182780 (ER antagonist). In conclusion, this study suggests that SERM raloxifene plus 17-βE2 improves the lipid metabolism and relieves the aorta changes of female experimental atherosclerosis rabbits, which are partly implemented by the inhibition of VSMC growth through ERK cascade. The hyperplasia of mammary gland epithelial cells could be significantly inhibited by raloxifene plus 17-βE2.

並列關鍵字

SERM ； raloxifene ； 17-βE2 ； atherosclerosis ； mammary gland ； VSMC ； ERK

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