电针对应激性前期高血压大鼠肾脏基因表达谱的影响研究

发布时间：2018-07-01 13:07

本文选题：电针 + 高血压前期　；参考：《北京中医药大学》2017年硕士论文

【摘要】：[研究目的]现代生活节奏的加快,工作压力和社会竞争性的增强,越来越多的人长期处于精神紧张焦虑状态使得应激性高血压的患病率逐年增加。2003年美国JNC-7第一次提出"高血压前期(Prehypertension)"即收缩压在120-139mmHg之间或舒张压在80-89 mmHg之间的阶段。研究表明高血压前期与心血管事件的发生呈正相关,甚至会开始有血管,心,脑,肾等靶器官损害。针刺干预可以在高血压前期这个关键阶段有效遏制高血压的发生并对肾脏等靶器官进行保护,为维护人类健康具有重要意义。本研究利用基因芯片技术、生物信息学分析技术深入探究电针对应激性高血压前期的干预效果及其干预机制,为高血压病的防治提供新的依据。[研究方法]将36只雄性Wistar大鼠(9周龄,220±30g)随机分为空白组,模型组和电针+模型3组,每组12只。运用足底电击结合噪声的刺激方法对模型组与电针组大鼠进行11天的造模,制备应激性高血压前期大鼠模型,并对电针组实施电针干预。分别在电针治疗前以及接受刺激后的第3、5、7、9、11天测量三组大鼠收缩压,并于造模和治疗结束后进行取材,采用Gene Chip Rat Gene 2.0 ST芯片技术检测三组大鼠肾组织基因表达谱的改变,筛选出差异表达基因(P0.05,Fold Changes1.5 or Fold Changes =-1.5)。运用 GO 功能富集分析(Gene Ontology)和 KEGG 通路富集分析(Kyoto Encyclopedia of Genes and Genomes)等生物信息学分析技术对差异基因进行生物学功能与通路的富集分析。[实验结果]造模开始后,空白组血压保持稳定;第3天,模型组血压开始上升120mm Hg,至第11天,血压持续升高(P0.01)。针刺干预第5天开始,针刺组血压低于模型组(P0.05)。针刺组血压虽然没有降至正常,但与模型组相比较差异有统计学意义(P0.05)。基因组注释(Genome annotation)是利用生物信息学方法和工具,对基因组所有基因的生物学功能进行高通量注释。GO功能富集分析把所有的差异表达基因映射到GO数据库的每个条目上,通过计算确定每个条目所对应的差异表达基因的数目,给出两样本间差异表达基因所参与的主要生物学功能,发现电针组与模型组的差异基因与氯离子通道复合体复杂离子通道,氯离子结合,氯离子通道活性,受体活性等功能有关。KEGG信号通路分析显示模型组有7条通路被激活,与模型组比较电针组有2条通路被激活。经文献检索发现神经受体通路(Neuroactive ligand-receptor action)与高血压发病及电针降压密切相关,并有GABRB3基因在此条通路上表达。根据电针组差异表达基因的分析可见GABRB3,CFTR,CISH基因,常出现在富集功能和信号通路中,经文献检索发现这3个基因和高血压的发病密切相关。电针降压机制可能是通过参与调控这3个关键基因的功能表达及其信号转导通路来实现.[实验结论]1.对应激性的高血压前期大鼠进行电针曲池和太冲穴的干预有降压效应。2.电针曲池和太冲穴影响应激性的高血压前期大鼠肾组织基因表达谱。3.电针曲池和太冲穴可能通过GABRB3,CFTR,CISH基因的调控和神经受体活性通路(Neuroactive ligand-receptor action)降压。
[Abstract]:[Objective] to accelerate the pace of modern life, work stress and social competitiveness, more and more people are in a state of prolonged mental anxiety and anxiety. The prevalence of stress hypertension has increased year by year in.2003, American JNC-7 first proposed "prehypertension (Prehypertension)" that is, systolic pressure is between 120-139mmHg or diastolic pressure. 80-89 mmHg stage. The study shows that prehypertension is positively related to the occurrence of cardiovascular events, and may even begin to damage target organs such as blood vessels, heart, brain and kidney. Acupuncture intervention can effectively restrain the occurrence of hypertension and protect the kidney and other target organs at this critical stage of prehypertension, which is important for the maintenance of human health. This study used gene chip technology and bioinformatics analysis technique to explore the intervention effect and intervention mechanism of electroacupuncture corresponding to pre induced hypertension in order to provide a new basis for the prevention and treatment of hypertension. [research methods] randomly divided 36 male Wistar rats (9 weeks old, 220 + 30g) into blank group, model group and electroacupuncture + model 3. In group 12, the model group and the electroacupuncture group were made for 11 days by the stimulation of the foot shock and the noise. The stress prehypertension rat model was prepared and the electroacupuncture intervention was carried out in the electroacupuncture group. The systolic pressure of three groups of rats was measured before the electroacupuncture treatment and the 3,5,7,9,11 day after the stimulation, and the model and treatment were made and treated. After the treatment, Gene Chip Rat Gene 2 ST chip was used to detect the changes of gene expression profiles in the renal tissue of three groups of rats, and the differential expression genes (P0.05, Fold Changes1.5 or Fold Changes =-1.5) were screened. Omes) and other bioinformatics analysis techniques to enrich the biological functions and pathways of the differential genes. [experimental results] the blood pressure in the blank group remained stable after the model was started. On the third day, the blood pressure of the model group began to rise 120mm Hg, and the blood pressure continued to rise (P0.01) at the end of the day (P0.01). The blood pressure in the acupuncture group was lower than the model group (P0.05) at the beginning of fifth days. The blood pressure in the acupuncture group was not reduced to normal, but the difference between the model group and the model group was statistically significant (P0.05). The genome annotation (Genome annotation) was the use of bioinformatics methods and tools to map all the differential expression genes to the GO number by high flux annotated.GO function enrichment analysis of the biological functions of all genes in the genome. According to each item of the library, the number of differentially expressed genes corresponding to each item was calculated, and the main biological functions of the differentially expressed genes between the two samples were given. The difference of the gene between the electroacupuncture group and the model group and the complex ion channel of the chloride channel complex, the chloride ion binding, the chloride channel activity, and the receptor were found. Activity and other function related.KEGG signaling pathway analysis showed that 7 pathways were activated in the model group. Compared with the model group, 2 pathways were activated in the electroacupuncture group. It was found that the neural receptor pathway (Neuroactive ligand-receptor action) was closely related to hypertension and electroacupuncture, and the GABRB3 gene was expressed in this pathway. According to the analysis of the differentially expressed genes in the electroacupuncture group, GABRB3, CFTR, and CISH genes are often found in the enrichment function and signal pathway. The 3 genes are closely related to the pathogenesis of hypertension through literature retrieval. The mechanism of electroacupuncture decompression may be realized by the function expression and signal transduction pathway involved in the regulation of the 3 key genes. Conclusion]1. corresponds to the intervention of Electroacupuncture of Qu Chi and Tai Chi in prehypertensive rats with induced hypertension. The gene expression profiles of renal tissue in prehypertensive rats with the effect of.2. electroacupuncture and Tai Chung acupoints.3. electroacupuncture Chi Chi and Tai Chung acupoint may be regulated by GABRB3, CFTR, CISH gene and neural receptor activity pathway (Neuroactive). Ligand-receptor action) depressurization.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R245

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