Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Reprod Sci. 2012 Jun;19(6):572-9. doi: 10.1177/1933719111430998. Epub 2012 Jan 19.
Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.
他汀类药物是内源性甲羟戊酸途径的有效抑制剂。除了抑制胆固醇生物合成外,他汀类药物还可能具有抗炎作用。炎症参与了子宫内膜细胞附着和侵入腹膜表面以及异位子宫内膜的生长,通过诱导增殖和血管生成。在这项研究中,评估了他汀类药物对裸鼠模型中子宫内膜异位症植入物和培养的子宫内膜异位症细胞中单核细胞趋化蛋白 1(MCP-1)表达的影响。在小鼠模型中,辛伐他汀以剂量依赖性方式降低子宫内膜异位症植入物中的 MCP-1 表达(P <.05)。同样,辛伐他汀和洛伐他汀均显示出对培养的子宫内膜异位症细胞中 MCP-1 产生的剂量依赖性抑制作用(P <.01)。他汀类药物对 MCP-1 产生的这种抑制作用可被甲羟戊酸途径的下游底物逆转。此外,他汀类药物降低了培养的子宫内膜异位症细胞中的 MCP-1 信使 RNA 表达(P <.05)。总之,他汀类药物在子宫内膜异位症细胞中发挥抗炎作用,将来可能为子宫内膜异位症提供一种潜在的治疗方法。