摘要
目的:探讨洛伐他汀对醛固酮诱导的大鼠心肌成纤维细胞增殖的影响及其作用机制。方法:采用胰酶消化法分离培养SpragueDawley大鼠心肌成纤维细胞,以3H胸腺嘧啶核苷(3HTdR)掺入法、四氮唑蓝比色法和流式细胞仪观察洛伐他汀对醛固酮诱导心肌成纤维细胞增殖的DNA合成、细胞数目和细胞周期的影响。结果:(1)0.1,1,10μmol·L-1浓度的洛伐他汀抑制醛固酮诱导的心肌成纤维细胞3HTdR掺入率和A490值,其中1,10μmol·L-1组的3HTdR掺入率[(1292±s152),(1030±163)counts·min-1]和A490值[(0.287±0.008),(0.231±0.007)]显著低于对照组、0.1和0.01μmol·L-1组(P<0.01);(2)洛伐他汀可增加G0/G1期细胞百分率,降低S期细胞百分率、增殖指数和DNA含量;(3)甲羟戊酸可逆转洛伐他汀的上述作用。结论:洛伐他汀可抑制醛固酮诱导的心肌成纤维细胞增殖及DNA合成,阻止其由G1期进入S期,其机制可能与甲羟戊酸代谢途径有关。
AIM: To investigate the effects of lovstatin on the proliferation of rats cardiac fibroblasts induced by aldosterone. METHODS: Cardiac fibroblasts of neonatal Sprague-Dawley rats were isolated with trypsin digestion method. 3H-TdR incorporation, MTT colorimetry and flow cytometric analysis were carried out to detect DNA synthesis, cell number and cell cycle, respectively. RESULTS: (1)Lovstatin (0.1,1,10 μmol·L -1) decreased 3H-TdR incorporation and A 490 values of cardiac fibroblasts (P<0.05). Moreover, 3H-TdR incorporation ((1 292±s 152), (1 030±163)counts·min -1) )and A 490 values(0.287± 0.008,0.231±0.007) of 1 μmol·L -1 lovastatin group and 10 μmol·L -1 lovastatin group were both lower than those of control group, 0.1 μmol·L -1 lovstatin group and 0.01 μmol·L -1 lovstatin group.(2)Lovstatin groups had increased percentage of cells in G 0/G 1 phase and reduced percentage of cells in S phase, PI values and DNA contents in a dose-dependent manner. (3) The inhibitory effect of lovstatin was almost completely reversed by mevalonate (1 mmol·L -1). CONCLUSION: The results indicate that lovstatin can significantly inhibit cardiac fibroblasts proliferation and DNA contents induced by aldosterone, provoke G 1/S transition arrest relating to inhibition of mevalonate pathway.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2005年第1期24-28,共5页
Chinese Journal of New Drugs and Clinical Remedies
