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羥基脲制作SD大鼠腎陽(yáng)虛證模型的規(guī)范化研究

發(fā)布時(shí)間:2018-11-14 11:56
【摘要】:一、研究目的 1.探索用羥基脲(Hydroxyacrbamide,Hu)制作SD大鼠腎陽(yáng)虛證動(dòng)物模型的具體方法,包括造模要素的選擇,造模過(guò)程的技術(shù)質(zhì)控,模型穩(wěn)定性研究、模型自然恢復(fù)期的研究,不同造模方法的比較研究等。為腎陽(yáng)虛證的實(shí)驗(yàn)和藥學(xué)研究提供較為標(biāo)準(zhǔn)的中醫(yī)證候動(dòng)物模型。 2.探索符合中醫(yī)學(xué)理論和經(jīng)驗(yàn)的腎陽(yáng)虛證大鼠模型評(píng)價(jià)體系,包括模型病因診斷、癥狀體征診斷、客觀指標(biāo)確立、治療反證等。為腎陽(yáng)虛證動(dòng)物模型和其他中醫(yī)證候動(dòng)物模型規(guī)范化研究提供參考。 二、研究方法 1.理論研究 系統(tǒng)回顧了中醫(yī)證候動(dòng)物模型的發(fā)展概況,對(duì)腎陽(yáng)虛證的基礎(chǔ)理論、腎陽(yáng)虛證動(dòng)物模型的制作方法等方面進(jìn)行了整理,對(duì)羥基脲腎陽(yáng)虛證動(dòng)物模型的研究現(xiàn)狀進(jìn)行了總結(jié)。 2.實(shí)驗(yàn)研究 2.1實(shí)驗(yàn)一:篩選羥基脲腎陽(yáng)虛證大鼠模型的造模方法 本實(shí)驗(yàn)選擇SPF級(jí)雄性SD大鼠,用文獻(xiàn)記載的用藥劑量:190mg/kg、280mg/kg、375mg/kg、450mg/kg造模,分別在第7天、12天、17天、22天連續(xù)采血,做出各劑量組動(dòng)物血清皮質(zhì)醇(Cort)、睪酮(T)、雌二醇(E_2)、甲狀腺素T_3和T_4、環(huán)磷酸腺苷(cAMP)、環(huán)磷酸鳥(niǎo)苷(cGMP)等各項(xiàng)指標(biāo)隨劑量、時(shí)間變化的動(dòng)態(tài)曲線,與空白對(duì)照組作對(duì)照,確定用藥劑量和給藥時(shí)間,篩選出較為規(guī)范的造模方法。 2.2實(shí)驗(yàn)二:羥基脲造模法對(duì)雄性SD大鼠癥狀及其它指標(biāo)的影響 按實(shí)驗(yàn)一篩選的造模方法造模,在造模過(guò)程中對(duì)動(dòng)物進(jìn)行一般情況的觀察,并進(jìn)行耐力耐寒試驗(yàn)、抓取激惹試驗(yàn)、跑步機(jī)試驗(yàn)、曠場(chǎng)試驗(yàn)、母鼠懷孕率等試驗(yàn),與空白對(duì)照組作對(duì)照。通過(guò)對(duì)癥狀的科學(xué)觀察,補(bǔ)充實(shí)驗(yàn)一客觀指標(biāo)檢測(cè)的不足,并進(jìn)一步完善腎陽(yáng)虛證動(dòng)物模型癥狀診斷評(píng)價(jià)體系。
[Abstract]:First, the purpose of the study 1. To explore the specific methods of making the animal model of kidney yang deficiency syndrome with hydroxyurea (Hydroxyacrbamide,Hu) in SD rats, including the selection of model elements, the technical quality control of model making process, the study of model stability, and the study of the natural recovery period of the model. Comparative study of different modeling methods. To provide a more standard animal model of TCM syndromes for the experimental and pharmacological study of kidney-yang deficiency syndrome. 2. To explore the evaluation system of rat model of kidney-yang deficiency syndrome in accordance with the theory and experience of traditional Chinese medicine, including model etiology diagnosis, diagnosis of symptoms and signs, establishment of objective indexes, treatment of adverse evidence, and so on. To provide a reference for the standardization of animal model of kidney yang deficiency syndrome and other animal models of TCM syndrome. Second, research method 1. The development of animal model of TCM syndromes was reviewed systematically, and the basic theory of kidney-yang deficiency syndrome and the method of making animal model of kidney-yang deficiency syndrome were sorted out. The present situation of research on the animal model of kidney yang deficiency syndrome with hydroxyurea was summarized. 2. Experimental study 2.1 experiment 1: screening the model of rat model of kidney yang deficiency syndrome with hydroxyurea. In this experiment, the male SD rats of SPF grade were selected. The dose recorded in the literature: 190mg / kg 280 mg / kg 250 mg 路kg ~ (-1) 路kg ~ (-1) 350 mg 路kg ~ (-1) 路kg ~ (-1). Blood samples were taken on the 7th, 12th, 17th and 22nd days, respectively, and the serum cortisol (Cort), testosterone (T), was made in each dose group. The dynamic curves of estradiol (E _ 2), thyroxine T _ 3 and T _ 4, cyclic adenosine (cAMP), cyclic guanosine phosphate (cGMP) with dose and time were compared with those of the blank control group. The dosage and time of administration were determined, and the more standard modeling method was screened out. 2.2 experiment 2: the effects of hydroxyurea modeling on symptoms and other indexes of male SD rats were studied according to the model making method selected in experiment 1, and the general conditions of the animals were observed during the course of modeling. Endurance cold tolerance test, grasping irritation test, treadmill test, open field test, pregnant rate of female mice were carried out, and compared with the blank control group. Through the scientific observation of the symptoms, the deficiency of the objective index detection was supplemented, and the diagnosis and evaluation system of the symptoms of the animal model of kidney yang deficiency syndrome was further improved.
【學(xué)位授予單位】:廣州中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2005
【分類(lèi)號(hào)】:R-332

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