Department of Cardiology, PLA No. 254 Hospital, Tianjin 300142, PR China.
Department of Cardiology, Laiwu Steel Group Co. Ltd, Laiwu 271100, PR China.
Biomed Pharmacother. 2018 Aug;104:240-251. doi: 10.1016/j.biopha.2018.04.179. Epub 2018 May 15.
Accelerated atherosclerosis in patients suffering from diabetes represents a major cause of morbidity and mortality. The aim of present study was to investigate the protective effects conferred by atorvastatin (AVT) meditated by the HMGCR gene in diabetic rats with atherosclerosis.
Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), fasting blood glucose (FBG) and serum insulin (INS) were all determined by means of in vivo experiments. Following the establishment of the diabetic model of atherosclerosis, the expressions of HMGCR, low density lipoprotein receptor (LDLR), fatty acid synthase (FASN) were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis in the vitro experiments. Flow cytometry was adopted in order to detect cell cycle and apoptosis.
The in vivo experiments results indicated that FBG and INS among the diabetic arteriosclerosis rats exhibited markedly higher levels; after injected with AVT and HMGCR, decreased contents of TC, TG, LDL-C and VLDL-C, while increased contents of HDL-C as well as an increased positive rate of HMGCR protein expression were observed. In vitro experiment, the mRNA and protein expression of LDLR were increased and FASN were decreased in cells transfected with HMGCR and AVT; with a greater number of cells arrested at the S phase and less in the G0/G1 phase, as well as data indicating the rate of apoptosis was inhibited after HMGCR and AVT transfection processes.
The key findings of the present study suggested that the protective effect conferred by AVT in diabetic rats with atherosclerosis was associated with the overexpression of the HMGCR gene, thus presenting a novel target for atherosclerosis treatment.
糖尿病患者的动脉粥样硬化加速是发病率和死亡率的主要原因。本研究旨在探讨阿托伐他汀(AVT)介导的 HMGCR 基因对动脉粥样硬化糖尿病大鼠的保护作用。
通过体内实验测定血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)、空腹血糖(FBG)和血清胰岛素(INS)。在建立动脉粥样硬化糖尿病模型后,通过逆转录定量聚合酶链反应(RT-qPCR)和 Western blot 分析检测体外实验中 HMGCR、低密度脂蛋白受体(LDLR)、脂肪酸合成酶(FASN)的表达。采用流式细胞术检测细胞周期和细胞凋亡。
体内实验结果表明,糖尿病动脉粥样硬化大鼠的 FBG 和 INS 水平明显升高;给予 AVT 和 HMGCR 后,TC、TG、LDL-C 和 VLDL-C 含量降低,HDL-C 含量升高,HMGCR 蛋白表达阳性率升高。体外实验中,转染 HMGCR 和 AVT 后 LDLR 的 mRNA 和蛋白表达增加,FASN 减少;转染 HMGCR 和 AVT 后,更多的细胞停滞在 S 期,更少的细胞停滞在 G0/G1 期,同时抑制了细胞凋亡率。
本研究的主要发现表明,AVT 对糖尿病动脉粥样硬化大鼠的保护作用与 HMGCR 基因的过表达有关,为动脉粥样硬化的治疗提供了新的靶点。