本文選題：高血壓大鼠　切入點(diǎn)：滋陰潛陽法　出處：《皖南醫(yī)學(xué)院》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:實(shí)驗(yàn)通過對(duì)二腎一夾腎性高血壓大鼠(2K1C-RHR)模型的復(fù)制,觀察滋陰潛陽方藥對(duì)模型大鼠的降壓作用,并觀察胸腺與脾臟中AT1R、PKA、CREB蛋白表達(dá)和血清中IL-2含量的變化。通過研究滋陰潛陽方藥對(duì)高血壓大鼠AT1受體介導(dǎo)的信號(hào)通路的影響,探討神經(jīng)、免疫、內(nèi)分泌三大系統(tǒng)在高血壓病的病理過程中發(fā)揮著整體作用及滋陰潛陽方藥在2H1C-RHR中的降壓機(jī)制,進(jìn)一步闡述滋陰潛陽方藥降壓、調(diào)節(jié)神經(jīng)免疫的作用靶點(diǎn)。方法:篩選復(fù)制成功的模型大鼠60只,隨機(jī)分為模型組、氯沙坦鉀組、天麻鉤藤組和滋陰潛陽低、中、高組,以及正常對(duì)照組與假手術(shù)組共8組,每組10只大鼠。分別對(duì)各組大鼠進(jìn)行相應(yīng)處理后,觀察檢測(cè)各項(xiàng)的客觀指標(biāo)。采用動(dòng)物無創(chuàng)血壓測(cè)量分析儀測(cè)量用藥前后大鼠的血壓,觀察各組大鼠的血壓變化情況;AT1R、CREB、PKA采用免疫組織化學(xué)法測(cè)定,IL-2采用ELISA法測(cè)定,HE染色觀察各組大鼠右腎的形態(tài)變化。數(shù)據(jù)統(tǒng)計(jì)方法:實(shí)驗(yàn)數(shù)據(jù)均以均數(shù)±標(biāo)準(zhǔn)差((?)±s)表示,多組間數(shù)據(jù)比較采用單因素方差分析,兩組間數(shù)據(jù)比較采用t檢驗(yàn),并且用SPSS18.0軟件包進(jìn)行處理,P0.05、P0.01為差異顯著,有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、滋陰潛陽法對(duì)2K1C-RHR收縮壓的影響:造模后2周,模型組及各用藥組大鼠的收縮壓均明顯升高,與假手術(shù)組、正常組比較,有統(tǒng)計(jì)學(xué)意義(P0.01);且SBP值≥160mm Hg,造模前后收縮壓差值絕對(duì)值≥20mm Hg,表明模型復(fù)制成功;用藥4周后,滋陰潛陽各劑量組(32、16、8g/kg)、氯沙坦鉀組和天麻鉤藤組大鼠SBP均明顯降低,與模型組比較,有統(tǒng)計(jì)學(xué)意義(P0.01)。2、滋陰潛陽法對(duì)2K1C-RHR腎組織病理學(xué)的影響:從腎臟的形態(tài)上觀察到,模型組右側(cè)受夾腎臟,與左側(cè)腎臟相比明顯萎縮,表面凹凸不平,壞死區(qū)域質(zhì)地較硬為灰黃色,未壞死區(qū)為暗紅色;左側(cè)腎臟表面光滑,呈暗紅色,體積較假手組明顯增大。從HE染色病理切片上顯示,模型組大鼠的腎小球萎縮趨勢(shì)明顯,腎小管發(fā)生變性并且排列紊亂;而滋陰潛陽方(低、中、高)組大鼠均有不同程度的改善。因而表明滋陰潛陽方各劑量組對(duì)腎臟具有一定的保護(hù)作用。3、滋陰潛陽法對(duì)2K1C-RHR血清IL-2的影響:模型組大鼠血清中IL-2含量明顯降低(P0.01);與模型組相比,各用藥組均能明顯升高血清中IL-2含量,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。4、滋陰潛陽法對(duì)2K1C-RHR胸腺、脾臟中AT1R、PKA和CREB表達(dá)的影響:(1)AT1R表達(dá)情況:模型組大鼠脾臟、胸腺中AT1R表達(dá)明顯升高(P0.01);與模型組相比,各用藥組均能降低脾臟、胸腺中AT1R表達(dá),差異有統(tǒng)計(jì)學(xué)意義(P0.01)。(2)PKA表達(dá)情況:模型組大鼠脾臟、胸腺中PKA表達(dá)明顯升高(P0.01);與模型組相比,各用藥組均能降低脾臟、胸腺中PKA表達(dá),差異有統(tǒng)計(jì)學(xué)意義(P0.01)。(3)CREB表達(dá)情況:模型組大鼠脾臟、胸腺中CREB表達(dá)明顯升高(P0.01);與模型組相比,各用藥組均能降低脾臟、胸腺中CREB表達(dá),差異有統(tǒng)計(jì)學(xué)意(P0.01)。結(jié)論:1、滋陰潛陽方具有較為顯著的降壓效果。2、滋陰潛陽方能夠保護(hù)靶器官腎臟。3、2K1C-RHR存在免疫系統(tǒng)調(diào)節(jié)的紊亂,滋陰潛陽方能夠提高外周血中炎癥因子IL-2水平,結(jié)合其對(duì)RAS系統(tǒng)的影響,表明滋陰潛陽方藥可能通過神經(jīng)免疫內(nèi)分泌系統(tǒng)的角度發(fā)揮其對(duì)機(jī)體的整體調(diào)節(jié)作用。4、滋陰潛陽方藥同時(shí)降低胸腺和脾臟AT1R、CREB、PKA的表達(dá),提示對(duì)淋巴細(xì)胞AT1受體介導(dǎo)的G蛋白-cAMP-PKA信號(hào)通路的影響可能是其對(duì)高血壓大鼠機(jī)體整體調(diào)節(jié)作用機(jī)制之一。
[Abstract]:Objective: through the experiment on two kidney one clip renal hypertensive rats (2K1C-RHR) model, observe the antihypertensive effect of Ziyin Qianyang Decoction on the rat model, and observe the AT1R, thymus and spleen in PKA, change of IL-2 content and expression of CREB protein in the serum. Through the influence of yin and Yang. The medicine on signal pathway of AT1 receptor induced hypertensive rats by the nerve, immunity, play the overall effect and mechanism of antihypertensive prescription of nourishing yin and Yang in the 2H1C-RHR three system in the pathological process of endocrine hypertension, further elaborated the Yin and Yang recipe buck, targets of regulation of neural immune. Copy the successful model: screening of 60 rats were randomly divided into model group, losartan group, Tianmagoutengyin group and Yin and Yang, low, high group and normal control group and sham operation group 8 group, 10 rats in each group. The rats were respectively. Should be treated objectively. The detection indexes were observed by animal noninvasive blood pressure of rats before and after blood pressure analyzer medication, blood pressure changes were observed; AT1R, CREB, PKA by immunohistochemistry assay, IL-2 was determined by ELISA method, to observe the morphological changes of the right kidney of the rats with HE staining methods: statistical data. The experimental data are mean standard deviation ((?) + s) said that the data were compared by single factor variance analysis, the data of the two groups were compared with t test, and SPSS18.0 software was used for processing, P0.05, P0.01 are significantly different, with statistical significance. Results: 1, Ziyinqianyang systolic blood pressure effects on 2K1C-RHR: 2 weeks after modeling, the systolic pressure of model group and each treatment group rats were significantly increased, and the sham operation group, normal group, with statistical significance (P0.01); and the SBP value is more than 160mm Hg, systolic blood pressure difference before and after modeling The absolute value is more than 20mm Hg, showed that the model was established successfully; after 4 weeks of medication, the Yin and Yang of each dose group (32,16,8g/kg), losartan group and Tianmagoutengyin rats in group SBP were significantly decreased, compared with the model group, there was statistical significance (.2, P0.01) Ziyinqianyang effect on 2K1C-RHR in renal tissue pathology study: from the kidney morphology observed in model group, the right kidney by the clip, compared with left renal atrophy, uneven surface, hard texture and gray areas of necrosis, no necrosis and dark red; the left kidney surface smooth, dark red, the volume was significantly higher than control group. HE staining showed that the pathological increase from section, glomerular atrophy trend of rats in model group obviously, renal tubular degeneration and arranged in disorder; and Ziyin Qianyang recipe (low, high) improved in different degree. So that group to have the Yin and yang side groups have on the kidney The protective effect of.3, effect of Ziyinqianyang on serum 2K1C-RHR IL-2: significantly decreased the serum levels of IL-2 rats in the model group (P0.01); compared with the model group, the treatment group can significantly increase the content of IL-2 in serum, the difference was statistically significant (.4, P0.01) Ziyinqianyang in 2K1C-RHR thymus. In the spleen of AT1R, expression of PKA and CREB: (1) the expression of AT1R in spleen of rats in the model group, the expression of AT1R was significantly increased in the thymus (P0.01); compared with the model group, the treatment group can reduce the expression of AT1R in spleen, thymus, the difference was statistically significant (P0.01) (2). The expression of PKA in spleen of rats in the model group, the expression of PKA was significantly increased in the thymus (P0.01); compared with the model group, the treatment group can reduce the expression of PKA in spleen, thymus, the difference was statistically significant (P0.01). (3) the expression of CREB in spleen model group rats significantly increased the expression of CREB in the thymus (P0.01) and model; Group, the treatment group can reduce the expression of CREB in spleen, thymus, there was statistically significant difference (P0.01). Conclusion: 1, yin and Yang has.2 significant antihypertensive effect, nourishing yin and yang can regulate the immune system disorders exist to protect the target organ of.3,2K1C-RHR in kidney, yin and yang to inflammatory factors the IL-2 level increased in the peripheral blood, combined with its impact on the RAS system, that Ziyin Qianyang decoction may regulate.4 by neuroimmunoendocrine system angle play an important role in the whole body, nourishing yin and Yang prescription while reducing the thymus and spleen AT1R, CREB, PKA expression, suggesting that effects on G protein -cAMP-PKA lymphocyte signaling pathway mediated by AT1 receptor may be the body of hypertensive rats overall adjustment mechanism.

【學(xué)位授予單位】：皖南醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R259

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