基于氧化应激探讨松龄血脉康对自发性高血压大鼠血管的保护机制
【摘要】探讨松龄血脉康胶囊对高血压状态下大鼠氧化应激损伤的保护作用及机制。将自发性高血压大鼠随机分为模型组、氯沙坦钾组、松龄血脉康高剂量组和、松龄血脉康常规剂量组，Wistar Kyoto大鼠（WKY）作为正常对照组，连续给药9周。生化法检测血清中氧化应激因子NO浓度、SOD活力、MDA含量。以Masson染色观察药物对大鼠主动脉病理组织形态学影响。借助qPCR阵列技术检测氧化应激相关因子RNA水平的变化，继而借助String及KEGG Pathway数据库对差异基因进行网络分析。与对照组比较，高血压模型组血清NO浓度明显降低（P<0.01），MDA浓度明显升高（P<0.05），提示自发性高血压大鼠血清氧化能力增强。给药后，与模型组比较，氯沙坦钾组、松龄血脉康大剂量组、松龄血脉康中剂量组MDA浓度均显著降低（P均<0.001）。各组间SOD活力未见明显变化（P>0.05）。qPCR阵列检测结果显示，与模型组比较，高剂量松龄血脉康组共得到9个差异倍数大于2的基因，其中Gch1、FOS、IGF1R基因表达量上调，PIK3CG、GPx2、CAV1、SOD1、PTEN、HSPA1B表达量下调。其中CAV1和IGF1R与氧化应激密切相关，松龄血脉康胶囊可能通过调节CAV1和IGF1R基因表达，减轻高血压状态下大鼠主动脉氧化应激损伤。
【关键词】松龄血脉康胶囊；自发性高血压大鼠；氧化应激
【中图分类号】R544.1 【文献标识码】A 【文章编号】ISSN.2095-6681.2018.6..04
【Abstract】To investigate the protective effect and mechanism of Songling Xuemaikang Capsule（SXC）on oxidative stress injury in spontaneously hypertensive rats（SHR）.SHR were randomly divided into model group，high dose SXC group （H-SXC），normal dose SXC group （ N-SXC） and losartan group，and WKY rats served as control.Rats were administered continuously for 9 weeks.Oxidative stress related factors including NO，SOD and MDA were detected by biochemical method.Masson staining was used to observe pathological morphology of the aorta.QPCR array technique was used to detect changes of oxidative stress related factors， and then network of differential genes were analyzed with String and KEGG Pathway databases. Compared with the control group， NO concentration of model group was significantly descended （P<0.01），and the concentration of MDA increased obviously （P<0.05）.Compared with model group，concentration of MDA in losartan group，H-SXC and N-SXC were decreased significantly（P<0.001）.There was no statistical significance for SOD activity in each group （P>0.05）.75 variable genes were screened through qPCR array detection.Compared with the model group，H-SXC group received 9 differentially expressed genes，which fold change was more than 2.And Gch1， FOS and IGF1R gene expression were up regulated， while PIK3CG， GPx2， CAV1，SOD1，PTEN and HSPA1B were down regulated.H-SXC can alleviate oxidative stress by regulating genes expression of CAV1 and IGF1R in hypertensive rats.
【Key words】Songling xuemaikang capsule；Spontaneously hypertensive rats；oxidative stress
血管收縮和舒张功能障碍是血压异常的关键环节，氧化应激是血管损伤的重要因素。越来越多的研究提示，氧化应激参与高血压病的发生和发展，其机制可能与氧化损伤血管内皮，影响血管功能有关[1-2]。这也提示，药物通过调节血管氧化应激水平、恢复血管功能，可能成为治疗高血压病新的探索方向。本课题组前期实验结果表明松龄血脉康胶囊能降低自发性高血压大鼠的血压[3]，同时提示其降压作用可能与抗氧化应激有关。故本研究借助qPCR阵列技术及String数据库，以自发性高血压大鼠为模型，进一步研究松龄血脉康对血管的保护作用，以期为松龄血脉康的临床应用提供参考。