【摘要】 背景从分子层面研究心肌重构相关基因可为左心室肥厚(LVH)的早期诊断及治疗提供新的思路与方法。长链非编码RNA(lncRNAs)虽然不编码蛋白质,但可在多个层面调控基因表达。目的采用微阵列技术分析原发性高血压病伴LVH患者lncRNA差异表达谱。方法随机选取2017年4—11月西安交通大学第二附属医院心内科住院部收治的原发性高血压病患者86例,根据左心室质量指数(LVMI)分为LVH组和无左心室肥厚组(NLVH组),每组43例。另选取同期本院与原发性高血压病患者性别、年龄相匹配的体检健康者43例作为健康对照组。每组选取3例患者,采用微阵列技术筛选血浆中差异表达的lncRNAs;采用实时荧光定量聚合酶链式反应(q-PCR)检测三组剩余患者血浆lncRNAs相对表达量;对差异表达显著的lncRNA进行编码-非编码基因共表达(CNC)分析,对差异表达显著的lncRNA的关联mRNA进行基因本体论分析(GO分析)和Pathway分析。结果与健康对照组、NLVH组比较,LVH组RP11-327F22.4相对表达量分别上调15.162、19.437倍(P<0.05),KHSRPP1相对表达量分别下调7.132、5.062倍(P<0.05)。q-PCR结果显示,LVH组和NLVH组RP11-327F22.4相对表达量高于健康对照组,LVH组RP11-327F22.4相对表达量高于NLVH组(P<0.05);LVH组和NLVH组KHSRPP1相对表达量低于健康对照组,LVH组KHSRPP1相对表达量低于NLVH组(P<0.05)。CNC分析结果显示,共挑出29种与KHSRPP1共表达的蛋白质编码基因,13种与RP11-327F22.4共表达的蛋白质编码基因(相关系数≥0.8,P≤0.05,FDR≤1)。GO分析结果显示,与RP11-327F22.4和KHSRPP1相关联的mRNA在分子功能层面主要富集在G蛋白偶联受体的激活与多肽受体的激活;与RP11-327F22.4和KHSRPP1相关联的mRNA在生物学过程层面主要富集在细胞激活和损伤的修复;与RP11-327F22.4和KHSRPP1相关联的mRNA在细胞组成层面主要富集在细胞周围与细胞膜。Pathway分析结果显示,与RP11-327F22.4和KHSRPP1相关联的mRNA主要富集在刺激神经组织的配体-受体相互作用路径与钙离子相关的信号路径。结论 RP11-327F22.4和KHSRPP1是原发性高血压病伴LVH患者血浆中差异表达显著的lncRNA,二者均可能成为预防和治疗原发性高血压病伴LVH的潜在靶点。更多还原

【Abstract】 Background The molecular study of myocardial remodeling related genes can provide new ideas and methods for the early diagnosis and treatment of left ventricular hypertrophy(LVH).Although long noncoding RNAs(lnc RNAs)do not encode any proteins,but they can regulate gene expression at multiple levels.Objective To analyze the differential expression profile of lnc RNAs in essential hypertension patients with LVH by using microarray technology. Methods A total of 86 patients with essential hypertension admitted to the Department of Cardiology,the Second Affiliated Hospital of Xi’an Jiaotong University from April to November 2017 were randomly selected,and they were divided into LVH group(n=43)or NLVH group(n=43)according to left ventricular mass index(LVMI). Another 43 healthy volunteers matched with gender and age of patients with essential hypertension in the same hospital were recruited as the healthy control group.The differentially expressed lnc RNAs in plasma were performed by microarray technology within three patients of each group;the relative expression of lnc RNA in the rest patients in three groups were detected by real-time quantitative polymerase chain reaction(q-PCR).The coding noncoding gene co-expression(CNC) analysis was performed for the differentially expressed lnc RNAs,and the gene ontology(GO)analysis and pathway analysis were performed on the related m RNAs of significantly differentially expressed lnc RNAs. Results Compared with healthy control group and NLVH group,the relative expression of RP11-327 F22.4 in LVH group was increased by 15.162 and 19.437 times,respectively(P<0.05);and the relative expression of KHSRPP1 was down regulated by 7.132 and 5.062 times,respectively(P<0.05).q-PCR results showed that the relative expression of RP11-327 F22.4 in LVH group and NLVH group was higher than that in healthy control group,and it was higher in LVH group than that in NLVH group(P<0.05). Furthermore,the relative expression of KHSRPP1 in LVH group and NLVH group was lower than that in healthy control group,while it was lower in LVH group than that in NLVH group(P<0.05).CNC analysis indicated that 29 coding protein genes co-expressed with KHSRPP1 and 13 coding protein genes co-expressed with RP11-327 F22.4 were found(correlation coefficient ≥ 0.8,P ≤0.05,FDR ≤1).GO analysis showed that m RNAs associated with RP11-327 F22.4 and KHSRPP1 were mainly involved in the activations of G-protein coupled peptide receptor and polypeptide receptor.Furthermore,the m RNAs associated with RP11-327 F22.4 and KHSRPP1 were mainly involved in cell activation and response to wounding in the biological process. Whilst,the m RNAs associated with RP11-327 F22.4 and KHSRPP1 were mainly rich in cell plasma membrane or periphery of cells. Pathway analysis discovered that m RNAs associated with RP11-327 F22.4 and KHSRPP1 were mainly concentrated in neuroactive ligand-receptor interaction and calcium signaling pathway. Conclusion RP11-327 F22.4 and KHSRPP1 are lnc RNA differentially expressed in plasma of essential hypertension patients with LVH,and both of them may be potential targets for the prevention and treatment of essential hypertension with LVH.更多还原