本文選題：慢性腎功能衰竭　切入點：復腎功方　出處：《重慶醫(yī)科大學》2016年碩士論文　論文類型：學位論文

【摘要】：背景:慢性腎功能衰竭(Chronic Renal Failure,CRF)是由先天或后天原因導致的慢性進行性腎實質損害,致使腎臟功能嚴重受損的臨床綜合征,主要表現為氮質血癥、代謝產物潴留、水電解質紊亂、酸堿平衡失調和全身各系統(tǒng)癥狀,為腎臟疾病持續(xù)發(fā)展的最終歸宿。據有關統(tǒng)計,全球終末期腎功能衰竭靠透析維持生命者多達360萬人,而中國各種腎臟病人有4000余萬人,每年新發(fā)生的慢性腎功能衰竭患者則有10-30萬人左右。有人預測,未來10年世界慢性腎功能衰竭患者治療費用至少需要1.1萬億美元,如此龐大的費用已使政府感到棘手。中醫(yī)藥防治慢性腎功能衰竭療效確切,而復腎功方是首屆國醫(yī)大師、著名中醫(yī)學家、全國名老中醫(yī)郭子光教授經過60余年來臨床驗證總結出來的、治療慢性腎功能衰竭確有卓著療效的經驗方。因此,研究復腎功方對CRF大鼠腎臟的保護作用,可為中醫(yī)藥治療CRF尋找新的治療靶點提供實驗依據,而本課題研究對于深入挖掘國醫(yī)大師臨床經驗具有十分重要的臨床實用價值、社會經濟價值及科學研究價值。目的:為了研究復腎功方對慢性腎功能衰竭大鼠腎臟的保護作用,本課題檢測了慢性腎功能衰竭大鼠腎組織α-SMA、E-cadherin及Nephrin等蛋白的表達,分別從抗腎纖維化、保護腎小管及足細胞等角度,探討復腎功方保護慢性腎功能衰竭大鼠腎臟的作用機制,以期為開發(fā)一個安全有效的治療crf的中成藥提供實驗基礎。方法:取雄性sd大鼠55只,適應性飼養(yǎng)1周后,隨機分為5組:正常組,模型組,復腎功方低、中、高劑量組,每組11只。正常組常規(guī)飼養(yǎng),其余各組大鼠食用含0.5%腺嘌呤飼料,每只大鼠按1天食入20g料塊計算,連續(xù)21d。造模21天后,隨機抽取各組大鼠1只,摘取眼球采血,分離血清,檢測scr和bun等指標以驗證造模是否成功。造模成功后,所有大鼠均停用含0.5%腺嘌呤的飼料,改用常規(guī)飼料。從造模成功后第1天起,正常組和模型組給予ns20ml?kg-1體重灌胃,復腎功方低、中、高劑量組分別以4、8、16g生藥?kg-1體重灌胃復腎功方煎劑,每日1次,連續(xù)30d。治療30d后,末次給藥后禁食不禁水12h,按20%烏拉坦5ml?kg-1進行麻醉,摘取眼球采血3-5ml,靜置1-2h,4000r?min-1離心10min,分離血清,取上清液,低溫4℃保存待檢測用。頸椎脫臼處死大鼠,打開腹腔取出腎臟,并做檢測前組織的相關處理。he染色和masson染色檢測腎組織形態(tài)學改變和腎間質纖維化程度,免疫組化及westernblotting檢測α-sma及e-cadherin蛋白的表達,免疫熒光及rt-pcr檢測nephrinmrna的表達。結果:與正常組比較,模型組大鼠腎組織α-sma表達明顯上調(p0.05),e-cadherin及nephrin表達明顯下調(p0.05);與模型組比較,復腎功方各劑量組腎組織α-sma表達明顯下調(p0.05),e-cadherin及nephrin蛋白表達則顯著上調(p0.05)。光鏡下正常組大鼠腎小管和腎小球結構正常,未見明顯組織學改變;模型組大鼠腎小球變形萎縮,球囊閉塞,腎小管萎縮,管腔明顯擴大,間質纖維化明顯,間質炎性細胞彌漫浸潤。經復腎功方治療后,復腎功方低劑量組大鼠腎小球、腎小管萎縮及間質纖維化有所減輕,間質炎性細胞彌漫浸潤;復腎功方中劑量組大鼠腎小球、腎小管萎縮及間質纖維化明顯減輕,間質炎性細胞浸潤減輕;復腎功方高劑量組大鼠腎臟病理改變顯著減輕,間質炎細胞浸潤明顯減輕。結論:復腎功方對CRF大鼠腎臟的保護作用,可能通過復腎功方抗腎纖維化、保護腎小管及足細胞等作用來實現的,其機制可能與復腎功方抑制腎組織α-SMA的表達,以及上調腎組織E-cadherin及Nephrin的表達有關。
[Abstract]:Background: chronic renal failure (Chronic Renal Failure, CRF) is caused by congenital or acquired causes chronic progressive renal damage, resulting in serious damage to renal function in clinical syndrome, mainly for azotemia, metabolite retention, electrolyte disturbances, acid-base imbalance and systemic symptoms, as the final incidence of kidney disease development. According to statistics, the global end-stage renal failure on dialysis to sustain life as many as 3 million 600 thousand people, and China all kidney patients more than 4000 people, chronic renal failure patients can occur each year there are about 10-30 million. It is predicted that the next 10 years the world in patients with chronic renal failure treatment costs at least $1 trillion and 100 billion, huge costs have made the government feel difficult. The curative effect of Chinese medicine in treating chronic renal failure and renal function exactly, is the first Chinese Medical University Division, national famous traditional Chinese medicine doctor, Professor Guo Ziguang after 60 years of clinical verification summed up the experience of the treatment of chronic renal failure has outstanding curative effect. Therefore, the research of complex renal function of renal protective effect of CRF rats for the TCM treatment of CRF to find new therapeutic targets for on the basis of experiment, and this research has very important clinical value for the dig Chinese medicine master clinical experience, social and economic value and scientific research value. Objective: To study the complex renal function of chronic renal failure rat renal protective effect, we detected the renal tissue of rats with chronic renal failure alpha -SMA, the expression of E-cadherin and Nephrin protein, respectively, from the anti renal fibrosis and protect renal tubular cells and foot angle, to investigate the chronic renal failure rat kidney complex mechanism of renal protection, in order to 涓哄紑鍙戜竴涓畨鍏ㄦ湁鏁堢殑娌葷枟crf鐨勪腑鎴愯嵂鎻愪緵瀹為獙鍩虹.鏂規(guī)硶:鍙栭泟鎬d澶ч紶55鍙，

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