本文選題：熊果酸 + 阿霉素腎病��； 參考：《福建醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的研究熊果酸對(duì)小鼠阿霉素腎病的影響，探討其可能的機(jī)制，為防止或延緩腎纖維化發(fā)展提供實(shí)驗(yàn)依據(jù)，同時(shí)為臨床防治腎纖維化尋求新的藥物。 方法將雄性Balb/c小鼠隨機(jī)分為4組，，即正常對(duì)照組（Normal組）、阿霉素腎病組（ADN組）、低劑量熊果酸干預(yù)組（LU+ADN組）、高劑量熊果酸干預(yù)組（HU+ADN組），每組10只。實(shí)驗(yàn)第4天，ADN組、LU+ADN組、HU+ADN組小鼠經(jīng)尾靜脈單次注射ADR10mg/Kg創(chuàng)建ADN模型，Normal組予等量生理鹽水。實(shí)驗(yàn)第1~18天，LU+ADN組、HU+ADN組分別予UA25mg/（Kg·d）、50mg/（Kg·d）腹腔注射，Normal組、ADN組予等量溶媒（14%DMSO）。造模后7天，收集24小時(shí)尿液，測(cè)定尿蛋白總量。造模后14天處死，留取血清檢測(cè)SCr、BUN、MDA，HE染色觀察腎臟病變情況，免疫組織化學(xué)法檢測(cè)TGF-β1在腎小管間質(zhì)中的表達(dá)，進(jìn)行半定量分析。 結(jié)果1.一般情況:造模后，ADN組小鼠狀態(tài)略差，進(jìn)食、活動(dòng)等有所減少，精神稍萎靡，LU+ADN組及HU+ADN組小鼠狀態(tài)無(wú)明顯變化。Normal組小鼠體重逐漸增長(zhǎng)。各組小鼠造模后，體重均明顯下降，不同劑量的UA對(duì)體重變化無(wú)明顯影響。2.小鼠24小時(shí)尿蛋白總量:ADN組小鼠較Normal組顯著升高（P＜0.05），HU+ADN組較ADN組顯著下降（P＜0.05）。3.腎功能：各組小鼠SCr、BUN差異均無(wú)統(tǒng)計(jì)學(xué)意義。4.血清MDA：注射ADR的三組小鼠較Normal組顯著升高（P＜0.01），兩治療組MDA水平與ADN組無(wú)顯著差異。5.HE染色: Normal組小鼠腎組織正常。ADN組腎臟表現(xiàn)為局灶性節(jié)段性腎小球硬化，腎小管上皮細(xì)胞腫脹，部分缺如，腎小管明顯擴(kuò)張，管腔內(nèi)充滿均質(zhì)紅染的蛋白管型，間質(zhì)形成纖維化病變；與ADN組相比，LU+ADN組腎臟病變改善不明顯，HU+ADN組腎臟病變較輕。6.免疫組化染色半定量分析:①與Normal組比，ADN組腎間質(zhì)表達(dá)TGF-β1顯著增加（P＜0.05）。②與ADN組比，LU+ADN組TGF-β1表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義；HU+ADN組小鼠TGF-β1表達(dá)顯著下降（P＜0.05）。 結(jié)論1、證實(shí)高劑量熊果酸（50mg/Kg）可以減少阿霉素腎病小鼠的尿蛋白。2、證實(shí)高劑量熊果酸可以抑制阿霉素腎病小鼠腎小管間質(zhì)TGF-β1蛋白的表達(dá)，抑制或延緩腎小球硬化、腎小管間質(zhì)纖維化進(jìn)展，發(fā)揮腎臟保護(hù)作用。3、本實(shí)驗(yàn)為熊果酸作為降低尿蛋白、抗腎纖維化新的藥物開(kāi)發(fā)提供了實(shí)驗(yàn)依據(jù)。
[Abstract]:Objective to study the effect of ursolic acid on adriamycin nephropathy in mice and explore its possible mechanism in order to provide experimental basis for preventing or delaying the development of renal fibrosis and to seek new drugs for clinical prevention and treatment of renal fibrosis. Methods male Balb/c mice were randomly divided into 4 groups: normal control group, adriamycin nephropathy group, low dose ursolic acid intervention group and high dose ursolic acid intervention group. On the 4th day of the experiment, the mice in the adn group were injected with ADR10mg/Kg through the tail vein to create the ADN model. The normal group was given the same amount of normal saline. The mice in the LU ADN group were given the same amount of normal saline by single injection of ADR10mg/Kg through the tail vein. In the first 18 days of the experiment, Hu ADN group was given 50 mg / g / kg UA25mg/(Kg dago in the ADN group, respectively) and the normal group was given the same amount of solute and 14DMSOO in the normal group. After 7 days, 24 hours urine was collected to determine the total amount of urine protein. The rats were killed 14 days after the model. The serum samples were collected to detect the pathological changes of kidney by SCrBUNMDAHE staining, and the expression of TGF- 尾 1 in renal tubulointerstitium was detected by immunohistochemical method, and the expression of TGF- 尾 1 in renal tubulointerstitium was detected by semi-quantitative analysis. Result 1. General conditions: after modeling, the mice in the ADN group were in poor state, eating and activities were decreased, and the mental state of the LU ADN group and Hu ADN group had no obvious change. The body weight of the normal group gradually increased. The body weight of each group of mice decreased significantly after modeling, and the changes of body weight were not affected by UA at different doses. Compared with Normal group, the total urine protein content in 24 hour group was significantly higher than that in Normal group (P < 0.05). The content of urine protein in ADN group was significantly lower than that in ADN group (P < 0.05). Renal function: there was no significant difference of SCrBUN in each group. 4. 4. Serum MDA: compared with the Normal group, the MDA level of the three groups was significantly higher than that of the Normal group (P < 0.01). There was no significant difference between the two groups in the level of MDA. 5. He staining showed that the renal tissue of the Normal group was normal. The kidney of the Normal group showed focal segmental glomerulosclerosis and tubule epithelial cells swelling. The renal tubules were dilated obviously, the tubules were filled with homogeneous red staining protein tubules, and the interstitial fibrosis lesions were formed in the tubules, and the renal lesions in the LU ADN group were not significantly improved compared with those in the ADN group, and the renal lesions in the Hu ADN group were less than that in the Hu ADN group. The expression of TGF- 尾 _ 1 in renal interstitial tissue of Normal group was significantly increased by immunohistochemical staining than that of Normal group (P < 0.05). There was no significant difference in TGF- 尾 _ 1 expression between LU ADN group and ADN group. The expression of TGF- 尾 _ 1 in HU ADN group was significantly lower than that in HU ADN group (P < 0.05). Conclusion 1. It is proved that high dose ursolic acid 50 mg / Kg can reduce urinary protein 0.2 in adriamycin nephropathy mice, and that high dose ursolic acid can inhibit the expression of TGF- 尾 1 protein in renal tubulointerstitial of adriamycin nephropathy mice and inhibit or delay glomerulosclerosis. The progress of renal tubulointerstitial fibrosis (tubulointerstitial fibrosis) plays a protective role in kidney. This experiment provides experimental basis for the development of ursolic acid as a new drug to reduce urinary protein and resist renal fibrosis.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R692

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