针刺捻转泻法对SI-PHT大鼠下丘脑基因表达谱影响的机理研究

发布时间：2018-02-09 19:12

本文关键词： 基因芯片捻转泻法下丘脑应激性高血压前期　出处：《北京中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的高血压的全球发病率持续上升,高发病率加重了个人、家庭和社会的负担。持续血压升高可导致靶器官心、脑、肾的损害,引起血管重塑,并伴全身的代谢性改变。如果没有及早发现并给予恰当的治疗,就会导致心肌梗死(MI)、脑卒中、肾衰以及死亡。除此之外,高血压还会促进其他疾病的发生发展。现实社会中各种应激源刺激促使高血压发生率升高。JNC-7首次提出"高血压前期"这一概念,其目的就是降低高血压的发生率,这与中医"未病先防"理念基本一致。基于此,本实验通过足底电击结合噪声刺激方法制备应激性高血压前期大鼠模型,以捻转泻法干预,从基因角度探究针刺捻转泻法对应激性高血压前期大鼠的作用机制。方法36只Wistar雄性大鼠随机分为空白组、模型组和捻转泻法组,每组12只。以足底电击结合噪声刺激方法造模,连续11天,空白组不造模。造模期间,每日对捻转泻法组大鼠双侧太冲、曲池行针刺捻转泻法操作,实验前1天,第3、5、7、9、11天测量各组收缩压,并观察行为学变化;11天后,以基因芯片技术检测分析各组下丘脑基因表达谱。结果整个实验过程,各组收缩压升幅均低于20mmHg;空白组收缩压无明显变化(P0.05);第3-11天,模型组和捻转泻法组收缩压均明显升高(与空白组相比,P0.01);第5-11天,捻转泻法组收缩压下降(与模型组相比,P0.01);模型组和捻转泻法组同时伴躁狂等行为学改变。与空白组比较,模型组出现246条异常表达基因,其中93条基因表达上调,153条基因表达下调。(|FC|1.5,P0.05)与模型组比较,捻转泻法组出现145条异常表达基因,其中59条基因表达上调,86条基因表达下调。(|FC|1.5,P0.05)40条基因在模型组与空白组、捻转泻法组与模型组的比较中出现相反表达(|FC|1.5,P0.05);其中,Acsm3、Cgα、CryαB 和 Tshβ 与高血压明显相关(|FC|1.5,P0.05);捻转泻法通过激活Autoimmune thyroid disease(AITD)通路发挥降压效应。结论通过针刺应激性高血压前期(SI-PHT)大鼠双侧太冲+曲池穴,施以捻转泻法,起到了对该模型大鼠的降压效应;同样条件下,经捻转泻法干预的应激性高血压前期大鼠发展为高血压病的风险低于模型组可能性较大。捻转泻法可引起SI-PHT大鼠下丘脑高血压相关基因Acsm3、Cgα、CryαB和Tshβ的差异表达,其可能的生物学机制为差异表达基因的生物学过程、分子功能发生变化,但造模期间的升压机制(模型组与空白组相比)与针刺捻转泻法的降压机制(捻转泻法组与模型组相比)可能不同。血压升高过程中,捻转泻法通过AITD通路实现降压效应,可能机制为甲状腺激素水平升高,引起血管阻力降低,进而导致该组血压升高进程较模型组慢。至于捻转泻法通过AITD通路发挥效应是否同时激活了与高血压发生相关的胰岛素抵抗机制尚不清楚,有待进一步研究。
[Abstract]:Objective the global incidence of hypertension continues to rise, and the high incidence increases the burden on individuals, families and society. A sustained increase in blood pressure can lead to damage to the heart, brain and kidney of the target organs, and to vascular remodeling. Without early detection and proper treatment, it can lead to myocardial infarction, stroke, renal failure, and death. Hypertension also promotes the occurrence and development of other diseases. In real society, various stressors stimulate the increase in the incidence of hypertension. JNC-7 first proposed the concept of "pre-hypertension", which aims to reduce the incidence of hypertension. This is basically consistent with the idea of "prevention before illness" in traditional Chinese medicine. Based on this, the rat model of stress-induced hypertension was established by plantar electric shock combined with noise stimulation, and the method of twirling and diarrhea was used to intervene. Methods 36 Wistar male rats were randomly divided into three groups: blank group, model group and twirling diarrhea group. 12 rats in each group were made by plantar shock combined with noise stimulation for 11 consecutive days, and no model was made in the blank group. During the modeling period, the rats in the twisting and catharsis group were treated with acupuncture twisting and catharsis every day, one day before the experiment. Systolic blood pressure (SBP) was measured in each group at day 3, 5, 5, 7, 9 and 11 days later. After 11 days of behavioral observation, gene expression profiles of hypothalamus in each group were detected and analyzed by gene chip technique. The increase of systolic blood pressure in each group was lower than 20mm Hg.There was no significant change in systolic blood pressure in blank group (P 0.05A). On the 3rd to 11th day, the systolic blood pressure in model group and twisting method group increased significantly (compared with the blank group, P 0.01; 5-11 days, respectively). Compared with the model group, the systolic blood pressure in the twisting and diarrhea group decreased (P 0.01), the behavior changes such as mania and mania in the model group and the twisting method group. Compared with the blank group, 246 abnormal expression genes were found in the model group. 93 genes were up-regulated and 153 genes were down-regulated. (FC 1.5P 0.05) compared with the model group, 145 abnormal genes were found in the twisting diarrhea group, and 59 genes were up-regulated and 86 genes were down-regulated. (FC 1.5P 0.05N 40 genes were expressed in the model group and the blank group, respectively). The reverse expression was found in the twisting diarrhea group and the model group (FC 1.5 P0.05, among which Acsm3Cg 伪 Cry 伪 B and Tsh 尾 were significantly correlated with hypertension (FC 1.5 P 0.05; twisting and diarrhea played a hypotensive effect by activating the Autoimmune thyroid disease AITD) pathway. Conclusion the SI-PHTs may be induced by acupuncture in prehypertensive patients. Bilateral Taichongqu Chi points in rats, The method of twirling and catharsis had the effect of lowering the blood pressure in the model rats; under the same conditions, The risk of developing hypertension in prehypertensive rats treated with twisting and reducing method was lower than that in the model group. Twist reduction method could induce the differential expression of hypothalamic hypertension related gene Acsm3Cg 伪 Cry 伪 B and Tsh 尾 in SI-PHT rats. Its possible biological mechanism is the biological process of differentially expressed genes and the change of molecular function. However, the pressor mechanism during modeling (model group compared with blank group) may be different from that of acupuncture twirling and reducing method (compared with model group). In the process of blood pressure rise, twisting diarrhea method can achieve hypotensive effect through AITD pathway. The mechanism may be the increase of thyroid hormone level and the decrease of vascular resistance. It is not clear whether the twisting method plays a role in activating the mechanism of insulin resistance associated with hypertension through the AITD pathway or not, which remains to be further studied.
【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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