他克莫司對激素耐藥型腎病綜合征患兒MDR1及其P-gp170表達的影響及意義

發(fā)布時間：2017-12-27 10:10

本文關(guān)鍵詞：他克莫司對激素耐藥型腎病綜合征患兒MDR1及其P-gp170表達的影響及意義　出處：《蘇州大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:檢測原發(fā)性腎病綜合征(INS)患兒不同時間點外周血單個核細胞(PBMC)多藥耐藥基因(MDR1)及其糖蛋白170(P-gp170)的表達情況,探討激素耐藥型腎病綜合征(SRNS)患兒加用他克莫司(TAC)治療后其MDR1及其P-gp170表達的變化和臨床意義。方法:選擇本院住院的原發(fā)性腎病綜合征(INS)患兒36例為研究對象,根據(jù)激素治療效果分成兩組:激素敏感型腎病綜合征(SSNS)組20例和激素耐藥型腎病綜合征(SRNS)組16例;20名健康體檢兒童作為正常對照組(control)。分四個時間點采集外周血標(biāo)本:(1)發(fā)病初未用糖皮質(zhì)激素(GC)時;(2)足量GC治療4周后;(3)SSNS組的GC減量4周后或SRNS組的加用TAC治療4周后;(4)SRNS組的加用TAC治療8周后。進行如下實驗:①實時定量逆轉(zhuǎn)錄聚合酶鏈?zhǔn)椒磻?yīng)(RT-PCR)檢測SRNS和SSNS不同時間點PBMC MDR1m RNA的表達。②流式細胞儀(FCM)檢測SRNS和SSNS不同時間點PBMC中淋巴細胞(Lymphocytes)上P-gp170的表達百分?jǐn)?shù)。③16例SRNS患兒均在激素治療4周后行腎穿刺活檢術(shù),10例正常腎組織為正常腎組織對照組,用免疫組織化學(xué)方法(IHC)檢測腎組織中P-gp170的表達。結(jié)果:(1)INS患兒PBMC MDR1m RNA與Lymphocytes P-gp170的表達呈高度正相關(guān)(r=0.854,P0.01)。(2)GC治療前,INS患兒PBMC MDR1m RNA與Lymphocytes P-gp170表達量均高于Control組,差異具有統(tǒng)計學(xué)意義(P0.05)。(3)足量GC治療4周后,SSNS組和SRNS組患兒PBMC MDR1m RNA及Lymphocytes P-gp170的表達均較治療前明顯升高,差異均具統(tǒng)計學(xué)意義(P0.01)。(4)GC減量4周后,SSNS患兒MDR1m RNA及Lymphocytes P-gp170的表達較前明顯回落,差異均具統(tǒng)計學(xué)意義(P0.01),而與GC治療前無明顯差異性(P0.05)。(5)加用TAC治療4、8周后,SRNS組患兒PBMC MDR1m RNA及Lymphocytes P-gp170的表達均較前明顯回落(P0.01),而加用TAC治療4周后的SRNS患兒兩指標(biāo)的表達量明顯高于GC減量4周后的SSNS患兒(P0.01)。(6)在SRNS組中,TAC治療8周后PBMC MDR1m RNA及Lymphocytes P-gp170的表達量明顯低于4周后(P0.01),且與GC治療前相比,無明顯統(tǒng)計學(xué)差異(P0.05)。(7)SRNS患兒與正常腎組織對照組兒童腎組織中P-gp170主要表達于腎小管及腎間質(zhì),SRNS組腎組織近曲小管和遠曲小管的P-gp170陽性率表達均明顯高于正常腎組織對照組(P0.01),SRNS組內(nèi)近曲小管P-gp170陽性率表達明顯高于遠曲小管(P0.01)。(8)足量GC治療4周后,SRNS患兒Lymphocytes P-gp170的表達量與腎組織近曲小管及遠曲小管P-gp170的表達量均呈正相關(guān)(r=0.547,P0.05;r=0.541,P0.05)。(9)GC治療前,SRNS組患兒PBMC P-gp170的表達量與24小時尿蛋白定量正相關(guān)(r=0.712,P0.01)。結(jié)論:(1)原發(fā)性腎病綜合征患兒PBMC MDR1m RNA與Lymphocytes P-gp170的表達呈高度正相關(guān),即MDR1m RNA表達量越高,其蛋白產(chǎn)物P-gp170表達量越高;(2)激素耐藥型腎病綜合征(SRNS)患兒PBMC MDR1m RNA及其蛋白產(chǎn)物P-gp170的高表達可能參與了激素耐藥的發(fā)生和發(fā)展;(3)SRNS患兒的腎組織P-gp170的高表達可能與激素耐藥有關(guān)。(4)他克莫司可在一定程度上減少SRNS患兒PBMC MDR1m RNA與P-gp170的表達量,可能為逆轉(zhuǎn)腎病綜合征患兒激素耐藥的機制之一。
[Abstract]:Objective: to detect the primary nephrotic syndrome (INS) patients at different time points of peripheral blood mononuclear cells (PBMC) multidrug resistance gene (MDR1) and glycoprotein 170 (P-gp170) expression, to explore the steroid resistant nephrotic syndrome (SRNS) patients with tacrolimus (TAC) and the clinical significance of changes of expression the MDR1 and P-gp170 after treatment. Methods: our hospital with primary nephrotic syndrome (INS) patients with 36 cases as the research object, according to the effect of hormone therapy were divided into two groups: steroid sensitive nephrotic syndrome (SSNS) group and 20 cases of steroid resistant nephrotic syndrome (SRNS) group of 16 cases; 20 healthy children as the normal control group (control). The peripheral blood samples were collected at four time points: (1) when the onset was not used Glucocorticoid (GC), (2) the full dose of GC was treated for 4 weeks; (3) the GC reduction in group SSNS was 4 weeks after treatment, or the SRNS group was treated with TAC for 4 weeks; (4) SRNS group was treated with TAC for 8 weeks. The following experiments were carried out: (1) real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of PBMC MDR1m RNA at different time points of SSNS. (2) flow cytometry (FCM) was used to detect the percentage of P-gp170 expression on the lymphocyte (Lymphocytes) in PBMC at different time points in SRNS and SSNS. (3) 16 children with SRNS underwent renal biopsy after 4 weeks of glucocorticoid treatment, and 10 normal kidney tissues were normal renal tissue control group. The expression of P-gp170 in renal tissue was detected by immunohistochemical method (IHC). Results: (1) the expression of PBMC MDR1m RNA in children with INS was highly correlated with the expression of Lymphocytes P-gp170 (r=0.854, P0.01). (2) before GC treatment, the expression of PBMC MDR1m RNA and Lymphocytes P-gp170 in children with INS was higher than that in Control group, and the difference was statistically significant (P0.05). (3) after 4 weeks of adequate GC treatment, the expressions of PBMC MDR1m RNA and Lymphocytes P-gp170 in SSNS group and SRNS group were significantly increased compared with those before treatment, and the differences were statistically significant (P0.01). (4) after 4 weeks of GC reduction, the expression of MDR1m RNA and Lymphocytes P-gp170 in SSNS children was significantly lower than before. The difference was statistically significant (P0.01), but there was no significant difference between GC and GC (P0.05). (5) after adding TAC for 4 or 8 weeks, the expression of PBMC MDR1m RNA and Lymphocytes P-gp170 in group SRNS was significantly lower than before (P0.01), while the expression of two index in SRNS children treated with TAC for 4 weeks was significantly higher than that in 4 children (4). (6) in group SRNS, after 8 weeks of TAC treatment, the expression of PBMC MDR1m RNA and Lymphocytes P-gp170 was significantly lower than that after 4 weeks (P0.01), and there was no significant difference compared with that before GC treatment (P0.05). (7) SRNS patients and normal renal tissues of children in control group P-gp170 in renal tissue was mainly expressed in renal tubular and interstitial, the positive rate of P-gp170 in renal tissue of SRNS group, the distal and proximal convoluted tubules expression were significantly higher than normal renal tissue of control group (P0.01), was significantly higher than the positive rate of proximal convoluted tubules tubular P-gp170 in the SRNS group (P0.01). (8) after 4 weeks of adequate GC treatment, the expression of Lymphocytes P-gp170 in SRNS children was positively correlated with the expression of P-gp170 in renal proximal tubules and distal tubules (r=0.547, P0.05, r=0.541, P0.05). (9) before GC treatment, the expression of PBMC P-gp170 in the children of group SRNS was positively correlated with the 24 hour urine protein (r=0.712, P0.01). Conclusion: (1) primary nephrotic syndrome in children with PBMC MDR1m RNA and Lymphocytes P-gp170 were highly correlated, MDR1m expression level of RNA is higher, the protein expression of P-gp170 is higher; (2) steroid resistant nephrotic syndrome (SRNS) patients with high expression of PBMC MDR1m RNA and its protein product P-gp170 may be involved in the occurrence and development of hormone resistance; (3) the high expression of SRNS in renal tissue of P-gp170 may be related to hormone resistance. (4) tacrolimus can reduce the expression of PBMC MDR1m RNA and P-gp170 to some extent in children with SRNS, which may be one of the mechanisms of reversing steroid resistance in children with nephrotic syndrome.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R726.9

【相似文獻】

相關(guān)期刊論文前10條

1 顧玲,劉霆,龔玉萍;mdr1單因素耐藥白血病細胞株的構(gòu)建[J];四川大學(xué)學(xué)報(醫(yī)學(xué)版);2005年04期

2 楊驊，曹江，胡汛，鄭樹，，董海濤;用逆轉(zhuǎn)錄多聚酶鏈反應(yīng)法檢測多藥耐藥基因（mdr1）的表達[J];浙江醫(yī)科大學(xué)學(xué)報;1995年02期

3 師以康;吳淑英;黃云虹;甄永蘇;;基因mdr1高表達多藥耐藥腫瘤細胞對力達霉素的藥物敏感性[J];藥學(xué)學(xué)報;2006年12期

4 彭志平;蔣明東;尹曉玲;文明;李少林;;反義寡脫氧核苷酸抑制多藥耐藥基因mdr1表達并逆轉(zhuǎn)耐藥肝癌細胞的體外試驗研究[J];中國藥房;2011年33期

5 黃鳳樓;刁孟元;俞云峰;張斌;;Mdr1基因的C3435T多態(tài)性及其臨床意義[J];海軍醫(yī)學(xué)雜志;2010年01期

6 梁川;吳緒峰;陳慧君;;卵巢癌中MDR1的表達及其臨床意義[J];腫瘤防治研究;2008年10期

7 喻龍姍;張開光;;MDR1在胃癌中的研究進展[J];國際消化病雜志;2012年06期

8 李琳;陳玉清;牛曉娜;張茵;王龍安;;實時熒光定量PCR檢測急性髓細胞白血病患者MDR1和WT1基因表達[J];臨床醫(yī)學(xué);2013年06期

9 林惠忠,陳磊,崔京遠,崔偉,周東風(fēng);多藥耐藥基因MDR1在乳腺癌中的表達及意義[J];中國現(xiàn)代普通外科進展;2005年01期

10 劉景坤;王曼;陸立;張哲;萬發(fā)義;;多藥耐藥基因MDR1在乳腺癌中的表達及意義[J];沈陽部隊醫(yī)藥;1999年04期

相關(guān)會議論文前9條

1 王東寧;黎國偉;黃仁魏;林桂真;林東軍;何易;李旭東;林曲;;急性非淋巴細胞白血病患者P73基因表達及與MDR1表達相關(guān)研究的臨床意義[A];中華醫(yī)學(xué)會第八次全國血液學(xué)學(xué)術(shù)會議論文匯編[C];2004年

2 封其華;楊玉京;宋曉翔;;兒童激素耐藥型腎病綜合征MDR1及P-gp170的表達及臨床意義[A];2012年江浙滬兒科學(xué)術(shù)年會暨浙江省醫(yī)學(xué)會兒科學(xué)分會學(xué)術(shù)年會、兒內(nèi)科疾病診治新進展國家級學(xué)習(xí)班論文匯編[C];2012年

3 封其華;付強;宋曉翔;;原發(fā)性腎病綜合征患兒外周血單個核細胞MDR1及P-gp170的表達[A];第六屆江浙滬兒科學(xué)術(shù)會議暨兒科學(xué)基礎(chǔ)與臨床研究進展學(xué)術(shù)班論文匯編[C];2009年

4 封其華;楊玉京;;兒童激素耐藥型腎病綜合征MDR1及P-gp170的表達及其臨床意義[A];中華醫(yī)學(xué)會第十五次全國兒科學(xué)術(shù)大會論文匯編（上冊）[C];2010年

5 封其華;楊玉京;宋曉翔;;兒童激素耐藥型腎病綜合征MDR1及P-gp170的表達及其臨床意義[A];中華醫(yī)學(xué)會第十七次全國兒科學(xué)術(shù)大會論文匯編（上冊）[C];2012年

6 趙珍珍;金先慶;宿玉璽;;多藥耐藥基因MDR1在體內(nèi)表達分布的實驗研究[A];中國西南地區(qū)第九屆小兒科學(xué)術(shù)會議論文匯編[C];2008年

7 雷瑚儀;趙謝蘭;;NF-κB活化及WT1、MDR1的表達在急性非淋巴細胞性白血病中的臨床意義[A];第10屆全國實驗血液學(xué)會議論文摘要匯編[C];2005年

8 盧振霞;畢林濤;;白血病CD34與MDR1表達的調(diào)控關(guān)系[A];2000全國腫瘤學(xué)術(shù)大會論文集[C];2000年

9 袁亞維;孫愛民;劉英;王志遠;陳龍華;;多藥耐藥基因(mdr1)啟動子-476位點CT變異與鼻咽癌放射敏感性的關(guān)系[A];中華醫(yī)學(xué)會放射腫瘤治療學(xué)分會六屆二次暨中國抗癌協(xié)會腫瘤放療專業(yè)委員會二屆二次學(xué)術(shù)會議論文集[C];2009年

相關(guān)博士學(xué)位論文前3條

1 石毓君;重組腺病毒載體攜帶mdr1反義RNA靶向逆轉(zhuǎn)肝癌細胞多藥耐藥的實驗研究[D];重慶醫(yī)科大學(xué);2004年

2 劉偉;Mdr1在腫瘤化療中療效及骨髓保護的實驗研究[D];重慶醫(yī)科大學(xué);2007年

3 徐近;胰腺癌中多藥耐藥基因MDR1的表達及其轉(zhuǎn)錄調(diào)控研究[D];復(fù)旦大學(xué);2005年

相關(guān)碩士學(xué)位論文前5條

1 楊金露;他克莫司對激素耐藥型腎病綜合征患兒MDR1及其P-gp170表達的影響及意義[D];蘇州大學(xué);2015年

2 付強;原發(fā)性腎病綜合征患兒外周血單個核細胞MDR1及P-gp170的表達[D];蘇州大學(xué);2009年

3 楊玉京;兒童激素耐藥型腎病綜合征MDR1及P-gp170的表達及臨床意義[D];蘇州大學(xué);2010年

4 楊趙娟;MDR1、p53及VEGF的表達與胃癌預(yù)后的相關(guān)性研究[D];遼寧醫(yī)學(xué)院;2011年

5 沈劍;Fas、MDR1與子宮頸癌化療敏感性及預(yù)后的關(guān)系[D];昆明醫(yī)學(xué)院;2003年

本文編號：1341270

資料下載