外周血RBP-4和尿IP-10、Mig、OPG含量在移植腎腎功能恢復(fù)和急性排斥反應(yīng)中的臨床研究
發(fā)布時(shí)間：2018-08-13 13:43
【摘要】：第一部分腎移植術(shù)后早期持續(xù)監(jiān)測(cè)外周血視黃醇結(jié)合蛋白-4的臨床意義 目的：探討腎移植術(shù)后受者早期外周血中視黃醇結(jié)合蛋白-4含量與移植腎功能恢復(fù)水平的相關(guān)性。 方法：采用回顧性巢式病例對(duì)照研究，將經(jīng)臨床診斷為急性排斥反應(yīng)的受者20例列為排斥組（AR組），腎功能延遲恢復(fù)者20列例為DGF組，腎功能恢復(fù)良好者20例列為對(duì)照組（Control組）。對(duì)60例患者的外周血視黃醇結(jié)合蛋白-4（RBP-4）、血肌酐（SCr）、血尿素氮（BUN）等三系Biomarker指標(biāo)，通過免疫透射比濁法、肌氨酸氧化酶法等操作平臺(tái)進(jìn)行持續(xù)動(dòng)態(tài)監(jiān)測(cè)，并對(duì)數(shù)據(jù)進(jìn)行縱橫對(duì)比分析。 結(jié)果：急性排斥組、腎功能延遲恢復(fù)組的RBP、Cr均明顯高于對(duì)照組，BUN的兩兩組間差異無統(tǒng)計(jì)學(xué)意義；急性排斥組中除BUN外其余指標(biāo)在處于排斥時(shí)間段內(nèi)與處于非排斥時(shí)間段內(nèi)有顯著性差異；腎功能延遲恢復(fù)組中，RBP、Cr在腎功能異常期的指標(biāo)與正常期指標(biāo)有顯著性差異；外周血視黃醇結(jié)合蛋白-4與血清肌酐、尿素氮成正相關(guān)；總之無論在急性排斥組還是在腎功能延遲恢復(fù)組，外周血視黃醇結(jié)合蛋白-4出現(xiàn)改變的時(shí)間均早于血肌酐變化的時(shí)間，在提示腎功能變化的時(shí)間上存在一定優(yōu)勢(shì)。 結(jié)論：外周血視黃醇結(jié)合蛋白-4在AR組、DGF組以及對(duì)照組中均與血清肌酐呈正性相關(guān)；臨床DGF嚴(yán)重程度與RBP-4含量高度相關(guān)，DGF越嚴(yán)重，外周血RBP-4測(cè)定值也越高；AR組中，RBP-4出現(xiàn)升高時(shí)間早于血肌酐變化，DGF組中，RBP-4出現(xiàn)下降的時(shí)間同樣早于血肌酐變化。最終本中心通過一系列持續(xù)序貫研究，認(rèn)為RBP-4為一獨(dú)立于血肌酐的Biomarker指標(biāo)，并希望其能廣泛應(yīng)用于早期腎移植術(shù)后人群腎功能的持續(xù)監(jiān)測(cè)中。 第二部分尿液IP-10、Mig和OPG檢測(cè)在移植腎急性排斥反應(yīng)中的應(yīng)用 目的：檢測(cè)患者尿液IP-10、Mig和OPG水平，探討這三個(gè)指標(biāo)在診斷移植腎急性排斥反應(yīng)中的臨床應(yīng)用價(jià)值。 方法：排斥組與對(duì)照組與第一部分受者相同，尿液樣本為同期同批次留取。對(duì)兩組術(shù)后連續(xù)30天的每天晨尿樣本，利用Luminex100流式熒光檢測(cè)儀和Plexmark三聯(lián)腎損傷標(biāo)志物試劑盒檢測(cè)30天內(nèi)每天的尿液IP-10、Mig和OPG的水平。并對(duì)兩組尿液中IP-10、Mig和OPG水平進(jìn)行統(tǒng)計(jì)學(xué)分析比較，是否在診斷移植腎急性排斥反應(yīng)中有意義。 結(jié)果：尿液IP-10和Mig水平在移植腎急性排斥腎功能損害的患者中均有高表達(dá)，OPG表達(dá)水平在兩組患者中無明顯差異。1、排斥組的尿液IP-10峰值水平為（317.10±61.99）pg/mL，明顯高于對(duì)照組的（5.33±1.40）pg/mL（P0.01)；排斥組的尿液Mig峰值水平為（451.00±29.01）pg/mL，亦明顯高于對(duì)照組的（22.16±5.96）pg/mL（P0.01)；排斥組尿OPG的峰值水平為（375.55±28.22）pg/mL，，對(duì)照組為（325.0±14.94）pg/mL，而兩組的差異無統(tǒng)計(jì)學(xué)意義（P0.05)。2、排斥組尿IP-10和Mig水平在不同的時(shí)刻與血肌酐濃度有較明顯的相關(guān)性，OPG與血肌酐未呈現(xiàn)明顯的相關(guān)性。IP-10水平與血肌酐濃度的相關(guān)性的決定系數(shù)R2=0.7835， P0.01； Mig水平與血肌酐濃度的相關(guān)性的決定系數(shù)R2=0.7731，P0.01；OPG水平與血肌酐濃度相關(guān)性的決定系數(shù)R2=0.0221，P0.05。3、排斥組在排斥時(shí)間段尿IP-10、Mig的水平顯著高于非排斥時(shí)間段尿IP-10、Mig的水平，尿OPG水平排斥前后差異無統(tǒng)計(jì)學(xué)意義。4、排斥組尿IP-10水平升高時(shí)間比血肌酐濃度升高時(shí)間提前（2.64±0.7426）天；尿液Mig水平升高比血肌酐濃度升高提前（2.6±0.7331）天。5、激素沖擊治療后，尿液IP-10、Mig從高表達(dá)急劇下降，比血肌酐濃度下降時(shí)間要早。 結(jié)論：1、尿液IP-10和Mig水平升高與移植腎急性排斥反應(yīng)相關(guān)，在腎功能損害到一定程度的患者中均有升高表達(dá)，是移植腎功能異常的動(dòng)態(tài)診斷指標(biāo)，尤其對(duì)急性排斥反應(yīng)、腎小管壞死有提前預(yù)示作用，且其升高的時(shí)間比血肌酐濃度升高時(shí)間早2-3天。2、尿液趨化因子IP-10和Mig表達(dá)水平，移植腎損害越嚴(yán)重，水平表達(dá)值越高，但隨著腎功能改善，水平表達(dá)值能靈敏的明顯下降，對(duì)激素沖擊治療效果的顯示時(shí)間比血肌酐顯示要早。3、尿液中各項(xiàng)生物學(xué)標(biāo)志物各有特點(diǎn)，同時(shí)存在自身的局限性。能否在今后的進(jìn)一步研究中，依據(jù)各指標(biāo)的優(yōu)缺點(diǎn)，建立聯(lián)合應(yīng)用的“biomark譜”。最終達(dá)到優(yōu)勢(shì)互補(bǔ)、預(yù)測(cè)病情、指導(dǎo)治療和監(jiān)測(cè)療效的目的。尿液IP-10和Mig水平檢測(cè)對(duì)于移植腎急性排斥有意義，可以提前預(yù)示移植腎急性排斥反應(yīng)，且能提前顯示激素沖擊治療效果，可以作為無創(chuàng)性、獨(dú)立指標(biāo)來預(yù)測(cè)急性排斥反應(yīng)的發(fā)生，并有顯示藥物治療效果的作用。
[Abstract]:Part I Clinical Significance of Early Continuous Monitoring of Retinol-binding Protein-4 in Peripheral Blood after Renal Transplantation
Objective: To investigate the correlation between retinol binding protein-4 (RBP-4) level in peripheral blood and renal function recovery in early stage after renal transplantation.
Methods: A retrospective nested case-control study was conducted. Twenty patients with acute rejection diagnosed clinically were classified as rejection group (AR group), 20 patients with delayed recovery of renal function as DGF group, and 20 patients with good recovery of renal function as control group (Control group). Urea nitrogen (BUN) and other three-system biomarker indicators were monitored continuously and dynamically by immune transmission turbidimetry, creatine oxidase and other operating platforms, and the data were compared and analyzed.
Results: RBP and Cr in acute rejection group and delayed renal function recovery group were significantly higher than those in the control group, and there was no significant difference between the two groups of BUN; RBP and Cr in acute rejection group were significantly different from those in non-rejection group except BUN; RBP and Cr in delayed renal function recovery group were significantly different from those in non-rejection group. Retinol binding protein-4 in peripheral blood was positively correlated with serum creatinine and urea nitrogen. In conclusion, the change of retinol binding protein-4 in peripheral blood was earlier than that of serum creatinine in acute rejection group and delayed recovery group. There is a certain advantage in time.
Conclusion: Retinol binding protein-4 in peripheral blood was positively correlated with serum creatinine in AR, DGF and control groups; the severity of clinical DGF was highly correlated with RBP-4 content; the more severe DGF was, the higher the RBP-4 level in peripheral blood was; RBP-4 increased earlier than serum creatinine in AR group, and RBP-4 decreased the same time in DGF group. Finally, through a series of continuous sequential studies, we concluded that RBP-4 is a biomarker independent of serum creatinine, and we hope it can be widely used in the continuous monitoring of renal function in early renal transplant recipients.
The second part is the application of urine IP-10, Mig and OPG in acute rejection of renal allograft.
Objective: To investigate the clinical value of urinary IP-10, Mig and OPG in the diagnosis of acute renal allograft rejection.
Methods:The urine samples of the rejection group and the control group were taken in the same batch at the same time.The urine samples of the two groups were collected at the same time.The urine levels of IP-10,Mig and OPG were detected by Luminex 100 flow fluorescence detector and Plexmark triple kidney injury marker kit for 30 days after operation. Statistical analysis and comparison of IP-10, Mig and OPG levels showed whether there was any significance in the diagnosis of acute rejection of renal allografts.
Results: Urinary IP-10 and Mig levels were significantly higher in patients with acute renal allograft rejection and no significant difference in OPG expression was found between the two groups. The peak level of urinary OPG in rejection group was (375.55+28.22) pg/mL, while that in control group was (325.0+14.94) pg/mL. There was no significant difference between the two groups (P 0.05). There was a significant correlation between the levels of urinary IP-10 and Mig in rejection group and serum creatinine concentration at different times. There was no significant correlation between serum creatinine and IP-10 level. The correlation between IP-10 level and serum creatinine concentration was determined by R2 = 0.7835, P 0.01; Mig level and serum creatinine concentration was determined by R2 = 0.7731, P 0.01; OPG level and serum creatinine concentration was determined by R2 = 0.0221, P 0.05.3, urinary IP-10, Mig in rejection group during rejection period. The levels of urinary IP-10 and Mig in rejection group were significantly higher than those in non-rejection group, and there was no significant difference before and after rejection of OPG. The increase of urinary IP-10 in rejection group was earlier than that of serum creatinine (2.64.7426) days; the increase of urinary Mig was earlier than that of serum creatinine (2.6.7331) days. P-10, Mig decreased dramatically from high expression, earlier than that of serum creatinine.
Conclusion: 1. Increased urinary IP-10 and Mig levels are associated with acute renal allograft rejection, and both of them are up-regulated in patients with renal impairment to a certain extent. They are dynamic diagnostic indicators of renal allograft dysfunction, especially for acute rejection and tubular necrosis, and their time of increase is longer than that of serum creatinine. The expression level of urine chemokine IP-10 and Mig was 2-3 days earlier. The more serious the renal allograft damage was, the higher the expression level was. However, with the improvement of renal function, the sensitivity of the expression level decreased significantly. The display time of hormone shock therapy was earlier than that of serum creatinine. Whether we can establish the biomark spectrum of combined application according to the merits and demerits of each index in the future research, and ultimately achieve the purpose of complementary advantages, predicting the condition, guiding the treatment and monitoring the curative effect. Repulsion can be used as a noninvasive, independent index to predict the occurrence of acute rejection, and has a significant effect of drug therapy.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R699.2
本文編號(hào)：2181165
[Abstract]:Part I Clinical Significance of Early Continuous Monitoring of Retinol-binding Protein-4 in Peripheral Blood after Renal Transplantation
Objective: To investigate the correlation between retinol binding protein-4 (RBP-4) level in peripheral blood and renal function recovery in early stage after renal transplantation.
Methods: A retrospective nested case-control study was conducted. Twenty patients with acute rejection diagnosed clinically were classified as rejection group (AR group), 20 patients with delayed recovery of renal function as DGF group, and 20 patients with good recovery of renal function as control group (Control group). Urea nitrogen (BUN) and other three-system biomarker indicators were monitored continuously and dynamically by immune transmission turbidimetry, creatine oxidase and other operating platforms, and the data were compared and analyzed.
Results: RBP and Cr in acute rejection group and delayed renal function recovery group were significantly higher than those in the control group, and there was no significant difference between the two groups of BUN; RBP and Cr in acute rejection group were significantly different from those in non-rejection group except BUN; RBP and Cr in delayed renal function recovery group were significantly different from those in non-rejection group. Retinol binding protein-4 in peripheral blood was positively correlated with serum creatinine and urea nitrogen. In conclusion, the change of retinol binding protein-4 in peripheral blood was earlier than that of serum creatinine in acute rejection group and delayed recovery group. There is a certain advantage in time.
Conclusion: Retinol binding protein-4 in peripheral blood was positively correlated with serum creatinine in AR, DGF and control groups; the severity of clinical DGF was highly correlated with RBP-4 content; the more severe DGF was, the higher the RBP-4 level in peripheral blood was; RBP-4 increased earlier than serum creatinine in AR group, and RBP-4 decreased the same time in DGF group. Finally, through a series of continuous sequential studies, we concluded that RBP-4 is a biomarker independent of serum creatinine, and we hope it can be widely used in the continuous monitoring of renal function in early renal transplant recipients.
The second part is the application of urine IP-10, Mig and OPG in acute rejection of renal allograft.
Objective: To investigate the clinical value of urinary IP-10, Mig and OPG in the diagnosis of acute renal allograft rejection.
Methods:The urine samples of the rejection group and the control group were taken in the same batch at the same time.The urine samples of the two groups were collected at the same time.The urine levels of IP-10,Mig and OPG were detected by Luminex 100 flow fluorescence detector and Plexmark triple kidney injury marker kit for 30 days after operation. Statistical analysis and comparison of IP-10, Mig and OPG levels showed whether there was any significance in the diagnosis of acute rejection of renal allografts.
Results: Urinary IP-10 and Mig levels were significantly higher in patients with acute renal allograft rejection and no significant difference in OPG expression was found between the two groups. The peak level of urinary OPG in rejection group was (375.55+28.22) pg/mL, while that in control group was (325.0+14.94) pg/mL. There was no significant difference between the two groups (P 0.05). There was a significant correlation between the levels of urinary IP-10 and Mig in rejection group and serum creatinine concentration at different times. There was no significant correlation between serum creatinine and IP-10 level. The correlation between IP-10 level and serum creatinine concentration was determined by R2 = 0.7835, P 0.01; Mig level and serum creatinine concentration was determined by R2 = 0.7731, P 0.01; OPG level and serum creatinine concentration was determined by R2 = 0.0221, P 0.05.3, urinary IP-10, Mig in rejection group during rejection period. The levels of urinary IP-10 and Mig in rejection group were significantly higher than those in non-rejection group, and there was no significant difference before and after rejection of OPG. The increase of urinary IP-10 in rejection group was earlier than that of serum creatinine (2.64.7426) days; the increase of urinary Mig was earlier than that of serum creatinine (2.6.7331) days. P-10, Mig decreased dramatically from high expression, earlier than that of serum creatinine.
Conclusion: 1. Increased urinary IP-10 and Mig levels are associated with acute renal allograft rejection, and both of them are up-regulated in patients with renal impairment to a certain extent. They are dynamic diagnostic indicators of renal allograft dysfunction, especially for acute rejection and tubular necrosis, and their time of increase is longer than that of serum creatinine. The expression level of urine chemokine IP-10 and Mig was 2-3 days earlier. The more serious the renal allograft damage was, the higher the expression level was. However, with the improvement of renal function, the sensitivity of the expression level decreased significantly. The display time of hormone shock therapy was earlier than that of serum creatinine. Whether we can establish the biomark spectrum of combined application according to the merits and demerits of each index in the future research, and ultimately achieve the purpose of complementary advantages, predicting the condition, guiding the treatment and monitoring the curative effect. Repulsion can be used as a noninvasive, independent index to predict the occurrence of acute rejection, and has a significant effect of drug therapy.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R699.2
【參考文獻(xiàn)】
相關(guān)期刊論文 前5條
1 蔣宇光;彭文翰;陳江華;;術(shù)前血清IP-10、Mig和BLC水平與移植腎排異關(guān)系的研究[J];內(nèi)蒙古醫(yī)學(xué)院學(xué)報(bào);2010年04期
2 張婉芬;張昌明;劉春蓓;秦衛(wèi)松;鄭春霞;曾科;劉志紅;;尿液microRNAs作為局灶節(jié)段性腎小球硬化疾病活動(dòng)生物標(biāo)志物的研究[J];腎臟病與透析腎移植雜志;2013年04期
3 ;Journal of Clinical Rehabilitative Tissue Engineering Research[J];Neural Regeneration Research;2011年15期
4 邢利;張翥;蔡文利;曲青山;苗書齋;王凱;;尿單核細(xì)胞趨化蛋白1與腎移植后急性排斥反應(yīng):有相關(guān)性嗎?[J];中國組織工程研究與臨床康復(fù);2010年05期
5 楊秀利;儲(chǔ)以微;鄧富剛;熊思東;;IP10對(duì)機(jī)體抗腫瘤免疫應(yīng)答的增強(qiáng)作用及其機(jī)制[J];中國免疫學(xué)雜志;2006年02期
本文編號(hào)：2181165
本文鏈接：http://sikaile.net/yixuelunwen/mjlw/2181165.html
最近更新
教材專著
