Tringali Giuseppe, Vairano Mauro, Dello Russo Cinzia, Preziosi Paolo, Navarra Pierluigi
Institute of Pharmacology, Catholic University Medical School, Largo Francesco Vito 1, 00168 Rome, Italy.
Neurosci Lett. 2004 Jan 9;354(2):107-10. doi: 10.1016/j.neulet.2003.09.066.
Statins were recently shown to possess anti-inflammatory activities, which might be responsible for their favourable effects in cardiovascular or CNS disorders independently from the inhibition of hydroxy-methyl-glutaryl CoA reductase. Here we investigated the effects of the statins lovastatin and mevastatin on prostanoid production in primary cultures of rat cortical microglia and astrocytes. We found that both statins significantly reduce prostaglandin E2 (PGE2) release from microglia, either under basal conditions or after stimulation by interleukin-1beta. Lovastatin also tends to reduce, although not in a significant manner, basal and interleukin-1beta-stimulated PGE2 release from astrocytes. Precursors and intermediates in cholesterol biosynthesis--mevalonic acid and geranyl and farnesyl pyrophosphate--also reduce PGE2 production, and potentiate the inhibitory effects of statins, suggesting that the latter might not depend on the inhibition of hydroxy-methyl-glutaryl CoA reductase.
他汀类药物最近被证明具有抗炎活性，这可能是它们在心血管或中枢神经系统疾病中产生有益作用的原因，而与抑制羟甲基戊二酰辅酶A还原酶无关。在此，我们研究了他汀类药物洛伐他汀和美伐他汀对大鼠皮质小胶质细胞和星形胶质细胞原代培养物中前列腺素生成的影响。我们发现，无论是在基础条件下还是在白细胞介素-1β刺激后，两种他汀类药物均能显著降低小胶质细胞中前列腺素E2（PGE2）的释放。洛伐他汀也倾向于降低星形胶质细胞基础状态下和白细胞介素-1β刺激后的PGE2释放，尽管降低幅度不显著。胆固醇生物合成的前体和中间体——甲羟戊酸、香叶基焦磷酸和法尼基焦磷酸——也能降低PGE2的生成，并增强他汀类药物的抑制作用，这表明他汀类药物的作用可能不依赖于对羟甲基戊二酰辅酶A还原酶的抑制。
