本文關(guān)鍵詞： 基因芯片 捻轉(zhuǎn)瀉法 下丘腦 應(yīng)激性高血壓前期　出處：《北京中醫(yī)藥大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的高血壓的全球發(fā)病率持續(xù)上升,高發(fā)病率加重了個(gè)人、家庭和社會(huì)的負(fù)擔(dān)。持續(xù)血壓升高可導(dǎo)致靶器官心、腦、腎的損害,引起血管重塑,并伴全身的代謝性改變。如果沒有及早發(fā)現(xiàn)并給予恰當(dāng)?shù)闹委?就會(huì)導(dǎo)致心肌梗死(MI)、腦卒中、腎衰以及死亡。除此之外,高血壓還會(huì)促進(jìn)其他疾病的發(fā)生發(fā)展。現(xiàn)實(shí)社會(huì)中各種應(yīng)激源刺激促使高血壓發(fā)生率升高。JNC-7首次提出"高血壓前期"這一概念,其目的就是降低高血壓的發(fā)生率,這與中醫(yī)"未病先防"理念基本一致。基于此,本實(shí)驗(yàn)通過足底電擊結(jié)合噪聲刺激方法制備應(yīng)激性高血壓前期大鼠模型,以捻轉(zhuǎn)瀉法干預(yù),從基因角度探究針刺捻轉(zhuǎn)瀉法對應(yīng)激性高血壓前期大鼠的作用機(jī)制。方法36只Wistar雄性大鼠隨機(jī)分為空白組、模型組和捻轉(zhuǎn)瀉法組,每組12只。以足底電擊結(jié)合噪聲刺激方法造模,連續(xù)11天,空白組不造模。造模期間,每日對捻轉(zhuǎn)瀉法組大鼠雙側(cè)太沖、曲池行針刺捻轉(zhuǎn)瀉法操作,實(shí)驗(yàn)前1天,第3、5、7、9、11天測量各組收縮壓,并觀察行為學(xué)變化;11天后,以基因芯片技術(shù)檢測分析各組下丘腦基因表達(dá)譜。結(jié)果整個(gè)實(shí)驗(yàn)過程,各組收縮壓升幅均低于20mmHg;空白組收縮壓無明顯變化(P0.05);第3-11天,模型組和捻轉(zhuǎn)瀉法組收縮壓均明顯升高(與空白組相比,P0.01);第5-11天,捻轉(zhuǎn)瀉法組收縮壓下降(與模型組相比,P0.01);模型組和捻轉(zhuǎn)瀉法組同時(shí)伴躁狂等行為學(xué)改變。與空白組比較,模型組出現(xiàn)246條異常表達(dá)基因,其中93條基因表達(dá)上調(diào),153條基因表達(dá)下調(diào)。(|FC|1.5,P0.05)與模型組比較,捻轉(zhuǎn)瀉法組出現(xiàn)145條異常表達(dá)基因,其中59條基因表達(dá)上調(diào),86條基因表達(dá)下調(diào)。(|FC|1.5,P0.05)40條基因在模型組與空白組、捻轉(zhuǎn)瀉法組與模型組的比較中出現(xiàn)相反表達(dá)(|FC|1.5,P0.05);其中,Acsm3、Cgα、CryαB 和 Tshβ 與高血壓明顯相關(guān)(|FC|1.5,P0.05);捻轉(zhuǎn)瀉法通過激活A(yù)utoimmune thyroid disease(AITD)通路發(fā)揮降壓效應(yīng)。結(jié)論通過針刺應(yīng)激性高血壓前期(SI-PHT)大鼠雙側(cè)太沖+曲池穴,施以捻轉(zhuǎn)瀉法,起到了對該模型大鼠的降壓效應(yīng);同樣條件下,經(jīng)捻轉(zhuǎn)瀉法干預(yù)的應(yīng)激性高血壓前期大鼠發(fā)展為高血壓病的風(fēng)險(xiǎn)低于模型組可能性較大。捻轉(zhuǎn)瀉法可引起SI-PHT大鼠下丘腦高血壓相關(guān)基因Acsm3、Cgα、CryαB和Tshβ的差異表達(dá),其可能的生物學(xué)機(jī)制為差異表達(dá)基因的生物學(xué)過程、分子功能發(fā)生變化,但造模期間的升壓機(jī)制(模型組與空白組相比)與針刺捻轉(zhuǎn)瀉法的降壓機(jī)制(捻轉(zhuǎn)瀉法組與模型組相比)可能不同。血壓升高過程中,捻轉(zhuǎn)瀉法通過AITD通路實(shí)現(xiàn)降壓效應(yīng),可能機(jī)制為甲狀腺激素水平升高,引起血管阻力降低,進(jìn)而導(dǎo)致該組血壓升高進(jìn)程較模型組慢。至于捻轉(zhuǎn)瀉法通過AITD通路發(fā)揮效應(yīng)是否同時(shí)激活了與高血壓發(fā)生相關(guān)的胰島素抵抗機(jī)制尚不清楚,有待進(jìn)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 偽 Cry 偽 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 偽 Cry 偽 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.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R245

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