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目的观察斯伐他汀(Simv)对佛波酯(PMA)诱导的人肾小球系膜细胞(HMC)A 型清道夫受体(SR-A)表达的作用。方法激光共聚焦显微镜检测HMC对荧光Dil标记的乙酰化低密度脂蛋白(Ac-LDL)的摄取。RT-PCR法检测HMC SR-A mRNA表达。瞬时转染带有SR-A 启动子片段的荧光素报告质粒,观察斯伐他汀对HMC SR-A启动子活性的影响。结果 (1)斯伐他汀(10μmol／L)明显抑制PMA(16．2 nmol／L)诱导的HMC对Dil-ac-LDL的摄取,100μmol／L 甲羟戊酸(Mev)基本阻断斯伐他汀的抑制作用。(2)斯伐他汀作用48 h,剂量依赖性(1-10 μmol／L)抑制PMA诱导的HMC SR-A mRNA表达,10 μmol／L组HMC SR-A mRNA表达量为对照组的54．7％;Mev可部分逆转斯伐他汀对SR-A mRNA的作用。(3)斯伐他汀抑制PMA诱导的 HMC SR-A启动子活性,处理组与对照组荧光素酶活性相比,差异具有统计学意义(P<0．01); 斯伐他汀加甲羟戊酸组荧光酶活性与对照组相比,无显著性差异。(4)斯伐他汀直接抑制转染 SR-A cDNA的人肾小球系膜细胞系SR-A mRNA表达。结论 (1)斯伐他汀抑制HMC SR-A 基因表达和活性可能为其延缓慢性肾小球疾病进展的机制之一;(2)斯伐他汀通过抑制甲羟戊酸代谢途径而抑制HMC SR-A的表达。
Objective To observe the effect of Simv on phorbol ester (PMA) -induced human mesangial cell (HMC) type A scavenger receptor (SR-A) expression. Methods Laser confocal microscopy was used to detect the uptake of fluorescent Dil-labeled acetylated low density lipoprotein (Ac-LDL) by HMC. The mRNA expression of SR-A in HMC was detected by RT-PCR. Fluorescein reporter plasmids carrying the SR-A promoter fragment were transiently transfected to observe the effect of simvastatin on the activity of the HMC SR-A promoter. Results (1) Stimvastatin (10 μmol / L) significantly inhibited the uptake of Dil-ac-LDL by PMA (16.2 nmol / L) induced HMC. Mevofloxacin (100 μmol / Inhibition of statins. (2) Stimulation of simvastatin for 48 h inhibited the PMA-induced mRNA expression of SR-A in HMC in a dose-dependent manner (1-10 μmol / L). The expression of SR-A mRNA in HMCs of 10 μmol / L group was 54% 7%. Mev partially reversed the effect of simvastatin on SR-A mRNA. (3) The inhibitory effect of simvastatin on PMA-induced HMC SR-A promoter activity was statistically significant (P <0.01). Compared with the control group, the difference was statistically significant (P <0.01) There was no significant difference in acid group fluorescence enzyme activity compared with the control group. (4) Simvastatin directly inhibits SR-A mRNA expression in human mesangial cell line transfected with SR-A cDNA. Conclusions (1) Inhibition of SR-A gene expression and activity by simvastatin may be one of its mechanisms to delay the progression of chronic glomerular disease. (2) Strovastatin inhibits the expression of HMC SR- A expression.