本文選題：參草通脈顆粒 + 慢性心力衰竭　； 參考：《遼寧中醫(yī)藥大學(xué)》2017年碩士論文

【摘要】：目的:本實驗通過建立大鼠心肌梗死后心衰模型,隨后分組灌服賴諾普利片和參草通脈顆粒復(fù)方的方法,觀察骨橋蛋白(osteopontin,OPN)在心肌組織及腎臟組織中的表達,探究慢性心力衰竭(chronic heart failure,CHF)的心腎相關(guān)機制,以及參草通脈顆粒對慢性心衰的干預(yù)作用,為中醫(yī)藥心腎同治治療慢性心衰的理念提供科學(xué)依據(jù)。材料與方法:1.制備慢性心衰大鼠模型:選用SPF級12周齡健康雄性SD大鼠6 0只,體重在230g~250g。其中預(yù)留1 5只大鼠進行假手術(shù)(開胸但不行冠狀動脈結(jié)扎),其余4 5只通過結(jié)扎大鼠冠狀動脈左前降支,配合術(shù)后減食、負荷運動的方式制備心肌梗死后慢性心衰大鼠模型。造模后經(jīng)由多普勒超聲心動圖計算,若大鼠左室射血分數(shù)(EF值)≤5 5%,同時動態(tài)心電圖顯示胸前導(dǎo)聯(lián)呈ST-T改變,并伴隨出現(xiàn)明顯精神萎靡,活動度減低,喜歡聚團,毛色無光、脫毛,飲食減少等慢性心衰體征即可納入實驗對象。2.實驗分組及喂養(yǎng):將慢性心衰模型造模成功的2 6只大鼠隨機分為模型組(8只)、中藥組(9只)、西藥組(9只),同時在假手術(shù)大鼠中隨機選取9只組成假手術(shù)組。假手術(shù)組及模型組不灌服藥物,每天給予常規(guī)等容積蒸餾水,劑量為3 ml/次,2次/日;中藥組給予參草通脈顆粒灌胃,劑量為每天每公斤9.2mg生藥;西藥組給予賴諾普利片灌胃,劑量為每天每公斤1.5 mg生藥。持續(xù)給藥喂養(yǎng)28天后再次行彩超檢測,檢測后將所有大鼠麻醉處死,取其血液、心肌組織、腎臟組織待檢。3.檢測方法:采用多普勒超聲心動圖檢測并計算各組大鼠LVID(ed)、LVID(es)、EF和FS數(shù)值,ELISA法測定大鼠血清中BNP濃度,采用Real-time PCR技術(shù)、免疫組化法分別測定假手術(shù)組、模型組、中藥組和西藥組大鼠OPN及OPN mRNA在心肌組織及腎臟組織中的表達水平,并在電鏡下觀察心肌組織形態(tài)結(jié)構(gòu)的改變。結(jié)果:1.模型組較假手術(shù)組LVID(ed)、LVID(es)均增高(P0.01),EF和FS均減低(P0.01);中藥組、西藥組與模型組相比LVI D(ed)、LVID(es)減低,EF、FS增高,組間變化顯著,差異均具有統(tǒng)計學(xué)意義(P0.01);中藥組同西藥組對比,各指標均無顯著差異,無統(tǒng)計學(xué)意義,(P0.05)。2.在心肌和腎臟組織中,模型組中OPN mRNA的表達與假手術(shù)組相比有著明顯升高,P=0.000(P0.01);藥物干預(yù)的兩組較模型組相比OPN mRNA的表達有所下降,差異有統(tǒng)計學(xué)意義(P0.01);中藥組和西藥組中OPN mRNA的表達差異不明顯,沒有統(tǒng)計學(xué)意義,P=0.878(P0.05)。3.較假手術(shù)組相對比,模型組中OPN在心肌和腎臟組織中的表達均明顯升高,組間差異明顯,P=0.000(P0.01);藥物治療的兩組較模型組相比,OPN明顯降低,差異有統(tǒng)計學(xué)意義,(P0.01);將經(jīng)由藥物治療的中藥及西藥組進行對比,OPN在心肌和腎臟組織中的表達差異均不明顯,無統(tǒng)計學(xué)意義,P0.05(心肌組織中p=0.804;腎臟組織中p=0.669)。4.模型組血清中的BNP表達有明顯的升高,約是假手術(shù)組的2.26倍,與假手術(shù)組對照P=0.000,(P0.01),兩組間有顯著差異;經(jīng)由藥物干預(yù)后,BNP的濃度明顯降低,與模型組比較,有統(tǒng)計學(xué)意義(P0.01);中藥組與西藥組組間比較效果相仿,差異無統(tǒng)計學(xué)意義(P0.05)。5.電鏡下觀察,假手術(shù)組心肌肌原纖維排列致密、整齊,明暗帶之間界限清晰整齊,線粒體數(shù)量豐富,其基質(zhì)排列緊密,內(nèi)脊排列致密整齊,形態(tài)清晰可見,糖原顆粒完整豐富;模型組心肌纖維排列紊亂不清,線粒體減少且明顯腫脹,內(nèi)脊結(jié)構(gòu)紊亂或消失,呈明顯空炮化,糖原數(shù)量也相應(yīng)減少;中藥組和西藥組心肌電鏡顯示,雖然心肌纖維排列紊亂,但勉強可見排列形態(tài),線粒體腫脹,內(nèi)脊結(jié)構(gòu)紊亂,較模型組中的一系列病理改變有所改善。結(jié)論:1.通過結(jié)扎大鼠冠狀動脈左前降支及術(shù)后減食、負荷運動的方法制作心肌梗死后慢性心衰模型方法穩(wěn)定可行,可應(yīng)用于慢性心衰的相關(guān)研究。2.通過對各組數(shù)據(jù)進行比較,證明參草通脈顆粒能夠通過下調(diào)心肌及腎臟組織中的OPN及OPN mRNA的表達,抑制心肌及腎臟的纖維化及重構(gòu)。3.通過本實驗可證明,參草通脈顆粒在慢性心力衰竭治療的臨床應(yīng)用上是安全有效的,能夠達到心腎同治的治療目的,其治療效果與賴諾普利相當。
[Abstract]:Objective: to establish a rat model of heart failure after myocardial infarction, and then to group a group of Lisinopril Tablets and Shen Cao Tongmai granule to observe the expression of osteopontin (OPN) in myocardial tissue and renal tissue, and to explore the mechanism of heart and kidney related to chronic heart failure (chronic heart failure, CHF), as well as Shen Cao Tong. The intervention of Mai Granule on chronic heart failure provides a scientific basis for the idea of treating chronic heart failure with Chinese medicine of heart and kidney. Materials and methods: 1. the rat model of chronic heart failure was prepared: 60 healthy male SD rats of SPF grade 12 weeks old were selected, and 15 rats were reserved in 230g~250g. for sham operation (open chest but not coronary artery ligation) The other 45 rats were prepared by ligating the left anterior descending branch of the coronary artery to prepare the rat model of chronic heart failure after myocardial infarction. After the model, the left ventricular ejection fraction (EF) was less than 55%, and the electrocardiogram showed ST-T changes in the prechest lead. The symptoms of chronic heart failure such as aggregation, hair coloring, hair loss, diet reduction and other chronic heart failure were included in.2. experimental group and feeding: 26 rats with chronic heart failure model were randomly divided into model group (8), Chinese medicine group (9) and Western medicine group (9 rats), and 9 randomly selected in the sham operation rats were randomly selected 9. The sham operation group was only made up of the sham operation group. The sham operation group and the model group did not take the medicine. The conventional equal volume distilled water was given daily, the dose was 3 ml/ times, 2 times per day. The Chinese medicine group gave Shencao Tongmai granule gavage, the dose was 9.2mg per kilo a day, and the western medicine group gave Lisinopril Tablets the stomach, the dose was 1.5 mg per kilo a day, and the continuous feeding was 28 days. After the test of color Doppler ultrasound, all rats were killed, and their blood, myocardial tissue and kidney tissue were examined by.3.. The LVID (ED), LVID (ES), EF and FS values were measured and calculated by Doppler echocardiography. ELISA method was used to determine the concentration of BNP in the serum of rats. Real-time PCR technique and immunohistochemical method were used respectively. The expression of OPN and OPN mRNA in the myocardium and kidney tissue of the rats in the sham operation group, the model group, the Chinese medicine group and the western medicine group were measured, and the changes of the morphological structure of the myocardium were observed under the electron microscope. Results: the 1. model group was higher than the sham operation group LVID (ED), LVID (ES) increased (P0.01), EF and FS decreased (P0.01); Chinese medicine group, western medicine group and model group phase Compared with LVI D (ED), LVID (ES), EF, FS increased, the changes between the groups were significant (P0.01), and there was no significant difference between the traditional Chinese medicine group and the western medicine group. (P0.05).2. in the myocardium and kidney tissue, the expression of OPN mRNA in the model group was significantly higher than that in the sham operation group. Compared with the model group, the expression of OPN mRNA decreased in two groups, and the difference was statistically significant (P0.01). There was no significant difference in the expression of OPN mRNA in the traditional Chinese medicine group and the western medicine group. The P=0.878 (P0.05).3. was compared with the sham group. The expression of OPN in the myocardium and kidney tissue in the model group was significantly higher than that in the model group, and the difference between the group and the group was different. Obviously, P=0.000 (P0.01); compared with the model group, the two groups of the drug treatment were significantly lower than the model group, and the difference was statistically significant (P0.01). Compared with the traditional Chinese medicine and the western medicine group, the difference in the expression of OPN in the myocardium and the kidney tissue was not obvious, no systematic significance, P0.05 (p=0.804 in the myocardium in the myocardium, p=0.669 in the kidney).4.. The expression of BNP in the serum of the model group was significantly increased, about 2.26 times of the sham operation group, compared with the sham group P=0.000, (P0.01), and there was a significant difference between the two groups. The concentration of BNP was significantly lower than that in the model group (P0.01), and the effect of the traditional Chinese medicine group and the western medicine group was similar, and the difference was not statistically significant. Under P0.05.5., the myofibrils of the sham operated group were densely arranged and neatly arranged in the sham operation group, with a clear and tidy boundary between the shades, rich mitochondria, tight matrix, dense and neatly arranged internal ridges, a clear and abundant form of the glycogen granules, the disorder of the myofibrils in the model group, and the decrease of mitochondria and obvious swelling of the myocardial fibers in the model group. The internal spinal structure was disorganized or disappeared, and the number of glycogen was reduced. The myocardium of the Chinese medicine group and the western medicine group showed that although the myocardial fibers were arranged in disorder, the arrangement form, the swelling of the mitochondria, the disorder of the internal spinal structure were barely visible, and a series of pathological changes in the model group were improved. Conclusion: 1. by ligating the coronary artery of the rats, the coronary artery was ligated. The method of making the model of chronic heart failure after myocardial infarction is stable and feasible to make the model of chronic heart failure after myocardial infarction. It can be applied to the related study of chronic heart failure. By comparing the data of each group,.2. can inhibit the expression of OPN and OPN mRNA in the myocardium and kidney tissue and inhibit the myocardium and kidney. .3. can be proved to be safe and effective in the clinical application of chronic heart failure in the treatment of chronic heart failure. It can achieve the goal of treating heart and kidney with the same treatment, and the effect of the treatment is equivalent to that of lisinopril.
【學(xué)位授予單位】：遼寧中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R285.5

【參考文獻】

相關(guān)期刊論文 前10條

1 曹景琳;林陽;仇琪;;心腎綜合征心腎相交理論的探討與辨析[J];環(huán)球中醫(yī)藥;2016年12期

2 丁萌;張青云;景陽;張秀琴;楊植;;炎性反應(yīng)因子及凝血因子在下肢深靜脈血栓形成中作用與相關(guān)性分析[J];臨床軍醫(yī)雜志;2016年11期

3 崔向男;楊洪濤;;心腎綜合征的中西醫(yī)研究進展[J];湖南中醫(yī)雜志;2016年10期

4 馬金;張艷;;益氣活血復(fù)方聯(lián)合運動訓(xùn)練對心衰大鼠心肌間質(zhì)及交感神經(jīng)重塑作用機制的研究[J];世界中西醫(yī)結(jié)合雜志;2016年09期

5 韓勇;賀滟;郭立榮;劉萬立;趙紅艷;何婭;;心肌缺血再灌注損傷大鼠中20-HETE對ROS生成及NADPH氧化酶活性的影響[J];現(xiàn)代醫(yī)藥衛(wèi)生;2016年18期

6 劉菊菊;李書國;鄧娟娟;葉明;張丹;彭燕;朱正庭;;高齡大鼠血管鈣化及血管壁骨橋蛋白、骨鈣素表達的研究[J];中國比較醫(yī)學(xué)雜志;2016年09期

7 戴力;王東俠;劉巖;;黃芪多糖對缺血性心肌病患者心功能的影響[J];山東醫(yī)藥;2016年36期

8 姜其鈞;龔志剛;李志剛;丁世芳;;乙醛脫氫酶2通過抗氧化減少氧化型低密度脂蛋白誘導(dǎo)的內(nèi)皮祖細胞凋亡[J];中國動脈硬化雜志;2016年09期

9 賀崢;張磊;金曉明;;腎纖維化發(fā)生的細胞及分子生物學(xué)機制研究進展[J];國際免疫學(xué)雜志;2016年05期

10 王靜靜;楊牧;尤可;;心腎綜合征發(fā)病機制的研究[J];中醫(yī)藥臨床雜志;2016年08期

相關(guān)博士學(xué)位論文 前1條

1 劉海潮;腎上腺髓質(zhì)素對血管緊張素II誘導(dǎo)的大鼠血管外膜成纖維細胞增殖、遷移、轉(zhuǎn)化及膠原生成的影響[D];華中科技大學(xué);2007年

，

本文編號：1957296