本文選題：雷公藤多苷片 + 蛋白尿�。� 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景在過去十年中,抗血管形成治療已廣泛應(yīng)用于臨床,貝伐珠單抗(bevacizumab,BEV)為新型抗血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)的人源化單克隆抗體,通過選擇性與VEGF結(jié)合,阻止VEGF與其受體的結(jié)合,阻斷下游信號通道,起到抗新生血管形成的作用,進(jìn)而抑制腫瘤生長。蛋白尿是貝伐珠單抗不良反應(yīng)之一,可導(dǎo)致抗血管形成治療中斷或延遲,嚴(yán)重蛋白尿患者則需要永久停止抗血管生成治療,嚴(yán)重影響臨床療效。多項(xiàng)研究表明雷公藤多苷片(Tripterysium wilfordii polyglucoside,TWP)可以通過保護(hù)足細(xì)胞改善糖尿病腎病的蛋白尿,在中-重度蛋白尿的治療中,發(fā)揮獨(dú)特優(yōu)勢,具有作用時(shí)間短、起效速度快、持續(xù)有效等特點(diǎn)。本研究觀察TWP對貝伐珠單抗誘導(dǎo)小鼠腎損傷的保護(hù)作用并探討其作用機(jī)制。目的研究血管形成抑制劑之一貝伐珠單抗誘導(dǎo)小鼠蛋白尿的形成機(jī)制,探索雷公藤對貝伐珠單抗誘導(dǎo)的小鼠蛋白尿的干預(yù)作用及可能作用機(jī)制。方法30只健康清潔級小鼠分為5組:Control組、BEV組(貝伐珠單抗60mg/kg·w-1i.v)、BEV+TWP1(BEV 60mg/kg·w-1 i.v+TWP 4mg/kg/d-1)、BEV+TWP2(BEV60mg/kg·w-1 i.v+TWP 8mg/kg/d-1)、BEV+TWP3(BEV 60mg/kg·w-1 i.v+TWP16mg/kg/d-1),Control組給予尾靜脈注射相同體積的生理鹽水。4周末收集小鼠24-h尿液,檢測尿蛋白總量;收集小鼠血液標(biāo)本,檢測血液中血肌酐(CREA)、尿素氮(BUN)、谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)等生化指標(biāo)。最后處死小鼠,留取腎組織,HE染色方法檢測腎組織病理變化,電鏡方法檢測足細(xì)胞超微結(jié)構(gòu),免疫組化、Western blot方法檢測腎組織VEGF、podocin、nephrin蛋白表達(dá),quantitative PCR方法檢測VEGF m RNA、podocin m RNA、nephrin m RNA表達(dá);結(jié)果BEV組24-h尿蛋白量顯著高于Control組;與BEV組比較,BEV+TWP2、BEV-TWP3組24-h尿蛋白量明顯減少,差異有統(tǒng)計(jì)學(xué)意義(P0.01);BEV+TWP1 24-h尿蛋白量無明顯差異。5組AST、ALT、BUN、GREA無明顯差異(P0.05)。腎組織病理變化:Control組小鼠腎組織結(jié)構(gòu)正常;BEV+TWP1組未見明顯病理改變;BEV組小鼠腎小球內(nèi)皮細(xì)胞萎縮,呈空泡狀結(jié)構(gòu)改變;BEV+TWP2、BEV-TWP3組腎小球結(jié)構(gòu)較BEV組明顯改善。電鏡下觀察到Control組小鼠腎組織呈正常結(jié)構(gòu)足細(xì)胞,而BEV組足細(xì)胞廣泛融合;BEV+TWP2、BEV-TWP3組小鼠足細(xì)胞較BEV組有明顯改善。免疫組化結(jié)果顯示Control組、BEV+TWP2、BEV-TWP3組小鼠腎組織VEGF的表達(dá)呈中、強(qiáng)陽性,BEV組小鼠呈弱陽性或陰性;在VEGF、nephrin、podocin蛋白及m RNA表達(dá)量方面,BEV組較Control組顯著下降,BEV+TWP2、BEV-TWP3較BEV組明顯升高,差異有統(tǒng)計(jì)學(xué)意義(P0.01);BEV+TWP1組無明顯差異(P0.05)。結(jié)論貝伐珠單抗下調(diào)VEGF、nephrin、podocin蛋白及m RNA表達(dá),從而損傷腎小球?yàn)V過膜,導(dǎo)致蛋白尿。而雷公藤多苷片具有促進(jìn)足細(xì)胞修復(fù)、減少蛋白尿的作用,其部分機(jī)制可能與提高VEGF、nephrin、podocin蛋白及m RNA表達(dá)量有關(guān)。
[Abstract]:Background in the past decade, anti-angiogenesis therapy has been widely used in clinical practice. Bevacizumab Bev) is a novel humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which binds selectively to VEGF. Blocking the binding of VEGF to its receptors, blocking downstream signal channels, and inhibiting angiogenesis, thus inhibiting tumor growth. Proteinuria is one of the adverse reactions of bevacizumab, which can lead to the interruption or delay of anti-angiogenesis therapy, while the severe proteinuria patients need to stop anti-angiogenesis therapy permanently, which seriously affects the clinical efficacy. A number of studies have shown that Tripterysium wilfordii polyglucoside TWP) can improve proteinuria in diabetic nephropathy by protecting podocytes. Tripterysium wilfordii polyglucoside can play a unique role in the treatment of moderate to severe proteinuria. Sustained effectiveness and so on. The aim of this study was to observe the protective effect of TWP on the renal injury induced by bevacizumab in mice and to explore its mechanism. Objective to study the mechanism of mouse proteinuria induced by bevacizumab, one of the angiogenesis inhibitors, and to explore the effect of Tripterygium wilfordii on mouse proteinuria induced by bevacizumab. Methods Thirty healthy clean mice were divided into 5 groups: the control group (60mg/kg w-1i.v TWP) TWP1(BEV 60mg/kg w-1 i.v TWP 4mg / kg / d -1 TWP 8mg / kg TWP3(BEV 60mg/kg w-1 i.v TWP 8mg / kg TWP3(BEV 60mg/kg w-1 i.v TWP16mgkgkg-1 + control group. The urine samples were collected for 24-h at the end of the week by injecting the same volume of physiological saline into the caudal vein. The serum creatinine (creatinine), urea nitrogen (bun), alanine aminotransferase (alt) and aspartate aminotransferase (AST) in blood of mice were detected. Finally, the mice were killed, the pathological changes of renal tissue were detected by HE staining, the ultrastructure of podocin was detected by electron microscopy, and the expression of VEGFpodocin nephrin protein was detected by immunohistochemical Western blot method. The expression of VEGF m RNApodocin m RNA-nephrin RNA was detected by quantitative PCR method. Results compared with BEV group, the urine protein content of BEV group was significantly higher than that of Control group, and that of BEV WP2BEV-TWP3 group was significantly lower than that of BEV group, and there was no significant difference in 24 h urinary protein content between BEV group and BEV group (P 0.05). There were no obvious pathological changes in the glomerular endothelial cells of the mice in the control group, and the glomerular structure in the BEV TWP2BEV-TWP3 group was significantly improved than that in the BEV group. The normal structure of podocyte was observed in the kidney of Control group under electron microscope, while the podocyte in BEV group was significantly improved compared with that in BEV group, and the podocyte fusion of BEV TWP2BEV-TWP3 group was better than that of BEV group. The results of immunohistochemistry showed that the expression of VEGF in the kidney tissue of the Control group was slightly positive or negative, and the expression of VEGF nephrinpodocin protein and m RNA in the BEV group was significantly lower than that in the Control group, and the expression of TWP2BEV-TWP3 in the BEV group was significantly higher than that in the BEV group. There was no significant difference in P0.01BV TWP1 group (P 0.05). Conclusion bevacizumab can down-regulate the expression of VEGF nephrinpodocin protein and m RNA, which may damage the glomerular filtration membrane and lead to proteinuria. However, Tripterygium wilfordii polyglycoside can promote podocyte repair and reduce proteinuria, which may be related to the increase of VEGF nephrinpodocin protein and m RNA expression.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R965

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 成遠(yuǎn);馬興群;江超;陳映霞;;雷公藤多苷治療貝伐珠單抗導(dǎo)致蛋白尿1例[J];現(xiàn)代腫瘤醫(yī)學(xué);2016年19期

2 江超;陳映霞;秦叔逵;楊愛珍;馬興群;成遠(yuǎn);曹夢苒;聞妹;;雷公藤多苷干預(yù)舒尼替尼引起的小鼠腎足細(xì)胞凋亡及相關(guān)蛋白表達(dá)的機(jī)制研究[J];安徽醫(yī)科大學(xué)學(xué)報(bào);2016年06期

3 蘆琨;劉國玲;沈永杰;宋瑋;李宜川;;雷公藤多苷對糖尿病腎病大鼠腎臟炎性損傷的保護(hù)作用[J];中藥藥理與臨床;2015年03期

4 陳衛(wèi)東;常保超;張燕;楊萍;劉磊;;雷公藤多苷對糖尿病大鼠腎組織缺氧誘導(dǎo)因子-1α及內(nèi)皮素-1表達(dá)的影響[J];南方醫(yī)科大學(xué)學(xué)報(bào);2015年04期

5 李平;皇甫春榮;湯春輝;;雷公藤多苷治療小兒紫癜性腎炎療效及對患兒免疫功能的影響[J];中國臨床藥理學(xué)雜志;2014年10期

6 劉國玲;沈永杰;尤麗菊;宋瑋;蘆琨;李宜川;;雷公藤多苷降低糖尿病腎病大鼠炎性細(xì)胞因子的表達(dá)[J];細(xì)胞與分子免疫學(xué)雜志;2014年07期

7 張奕星;袁斌;徐建亞;周立華;孔飛;武青;;丹芍顆粒Ⅲ對紫癜性腎炎大鼠血尿、蛋白尿和腎組織nephrin及podocin的影響[J];醫(yī)學(xué)研究生學(xué)報(bào);2014年04期

8 賈守薇;劉韜;黃紅兵;;分子靶向抗腫瘤藥物的不良反應(yīng)及其處理對策[J];腫瘤藥學(xué);2014年01期

9 趙靜;李航;張力;鐘巍;李龍蕓;文煜冰;王孟昭;;四例貝伐單抗所致腎損害臨床和病理特征分析[J];中國醫(yī)學(xué)科學(xué)院學(xué)報(bào);2012年02期

10 葛永純;謝紅浪;李世軍;侯金花;章海濤;史明君;劉志紅;;雷公藤多苷治療糖尿病腎病的前瞻性隨機(jī)對照臨床試驗(yàn)[J];腎臟病與透析腎移植雜志;2010年06期

相關(guān)會(huì)議論文 前1條

1 董興剛;;雷公藤治療蛋白尿30年回顧與展望[A];第五屆全國雷公藤學(xué)術(shù)會(huì)議論文匯編[C];2008年

，

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