Clusterin蛋白和Bim蛋白在非梗阻性无精症睾丸组织中的表达及意义
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摘要
目的探讨Clusterin蛋白和Bim蛋白在非梗阻性无精症睾丸组织中的表达及意义。方法收集2014年2月至2018年8月广东省计划生育科学技术研究所的32例非梗阻性无精症睾丸组织标本作为无精症组,外伤切除睾丸组织标本30例作为对照组,采用免疫组织化学法检测各组睾丸组织Clusterin蛋白和Bim蛋白的表达情况,比较各组表达阳性率和表达强度。结果非梗阻性无精症患者睾丸组织内Clusterin蛋白和Bim蛋白主要在生精细胞胞质内表达,阳性表达者表现为生精细胞内极细胞膜不均匀颗粒样或团块样棕褐色染色物质。无精症组Clusterin蛋白表达阳性率低于对照组[65. 6%(21/32)比100. 0%(30/30)](P <0. 05)。无精症组Bim蛋白表达阳性率高于对照组[56. 3%(18/32)比26. 7%(8/30)](P <0. 05)。相关分析结果显示,非梗阻性无精症睾丸组织中Clusterin蛋白与Bim蛋白表达呈负相关(rs=-0. 391,P=0. 004)。结论非梗阻性无精症患者睾丸组织存在Clusterin蛋白表达缺失及Bim蛋白过表达现象,其可能与少精子症的发生、进展有关,并且Clusterin蛋白及Bim蛋白可能存在相互调控关系。
Objective To investigate expression of Clusterin protein and Bim protein in testicular tissue of nonobstructive azoospermia and analyze its clinical significance. Methods A total of 32 cases of testicular tissue specimens with non-obstructive azoospermia in Science and Technology Research Institute of Family Planning in Guangdong Province were selected from Feb. 2014 to Aug. 2018,and were divided into an azoospermia group( n = 32),while 30 normal testicular tissue specimens were selected as a control group( n = 30). Expression of Clusterin and Bim protein in testicular tissue of each group was detected by immunohistochemistry. Positive rate and expressive intensity of Clusterin and Bim protein were compared between the groups. Results In non-obstructive azoospermia patients,Clusterin protein and Bim protein were mainly expressed in the cytoplasm of spermatogenic cells,and those with positive expression showed heterogeneous granular or mass-like brownish staining substance in the inner polar cell membrane of spermatogenic cells. Positive rate of Clusterin protein was lower in the azoospermia group than that in the control group[65. 6%( 21/32) vs 100. 0%( 30/30) ]( P <0. 05). Positive rate of Bim protein was higher in the azoospermia group than that in the control group[56. 3%( 18/32) vs26. 7%( 8/30) ]( P < 0. 05). Correlation analysis showed that there was a negative correlation between expression of Bim and Cluster in non-obstructive azoospermia( rs=-0. 391,P = 0. 004). Conclusion Bim protein is over expressed and Clusterin expression is loss in testicular tissues of non-obstructive azoospermia patients,which may be related to occurrence and progression of oligospermia,and there may be mutual regulation between Clusterin protein and Bim protein.
Objective To investigate expression of Clusterin protein and Bim protein in testicular tissue of nonobstructive azoospermia and analyze its clinical significance. Methods A total of 32 cases of testicular tissue specimens with non-obstructive azoospermia in Science and Technology Research Institute of Family Planning in Guangdong Province were selected from Feb. 2014 to Aug. 2018,and were divided into an azoospermia group( n = 32),while 30 normal testicular tissue specimens were selected as a control group( n = 30). Expression of Clusterin and Bim protein in testicular tissue of each group was detected by immunohistochemistry. Positive rate and expressive intensity of Clusterin and Bim protein were compared between the groups. Results In non-obstructive azoospermia patients,Clusterin protein and Bim protein were mainly expressed in the cytoplasm of spermatogenic cells,and those with positive expression showed heterogeneous granular or mass-like brownish staining substance in the inner polar cell membrane of spermatogenic cells. Positive rate of Clusterin protein was lower in the azoospermia group than that in the control group[65. 6%( 21/32) vs 100. 0%( 30/30) ]( P <0. 05). Positive rate of Bim protein was higher in the azoospermia group than that in the control group[56. 3%( 18/32) vs26. 7%( 8/30) ]( P < 0. 05). Correlation analysis showed that there was a negative correlation between expression of Bim and Cluster in non-obstructive azoospermia( rs=-0. 391,P = 0. 004). Conclusion Bim protein is over expressed and Clusterin expression is loss in testicular tissues of non-obstructive azoospermia patients,which may be related to occurrence and progression of oligospermia,and there may be mutual regulation between Clusterin protein and Bim protein.
引文
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[13]Dubey SK,Hejtmancik JF,Krishnadas SR,et al.Evaluation of genetic polymorphisms in clusterin and tumor necrosis factoralpha genes in South Indian individuals with pseudoexfoliation synd-rome[J].Curr Eye Res,2015,40(12):1218-1224.
[14]Plotton I,Sanchez P,Durand P,et al.Decrease of both stem cell factor and clusterin mRNA levels in testicular biopsies of azoospermic patients with constitutive or idiopathic but not acquired spermatogenic failure[J].Hum Reprod,2006,21(9):2340-2345.
[15]Salehi M,Akbari H,Heidari MH,et al.Correlation between human clusterin in seminal plasma with sperm protamine deficiency and DNA fragmentation[J].Mol Reprod Dev,2013,80(9):718-724.
[16]Fukuda T,Miyake H,Enatsu N,et al.Seminal level of clusterin in infertile men as a significant biomarker reflecting spermatogenesis[J].Andrologia,2016,48(10):1188-1194.
[17]O'Bryan MK,Baker HW,Saunders JR,et al.Human seminal clusterin(SP-40,40).Isolation and characterization[J].J Clin Invest,1990,85(5):1477-1486.
[18]Grabow S,Kueh AJ,Ke F,et al.Subtle Changes in the Levels of Bcl-2 Proteins Cause Severe Craniofacial Abnormalities[J].Cell Rep,2018,24(12):3285-3295.
[19]Lin X,Shen J,Dan P,et al.RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells[J].Signal Transduct Target Ther,2018,31(3):23-29.
[20]Yue D,Sun X.Idelalisib promotes Bim-dependent apoptosis through AKT/Fox O3a in hepatocellular carcinoma[J].Cell Death Dis,2018,9(10):935-943.
[2]Ali MH,Soliman M,Metwally A,et al.Cytogenetic analysis and endocrine profile in patients with nonobstructive azoospermia or severe oligozoospermia[J].Afr J Urol,2018,24(3):212-215.
[3]林云华,姜永光,方微,等.Bim1在前列腺癌中的表达及临床意义[J].首都医科大学学报,2016,37(3):323-326.
[4]Liu G,Zhang H,Hao F,et al.Clusterin Reduces Cold IschemiaReperfusion Injury in Heart Transplantation Through Regulation of NF-κB Signaling and Bax/Bcl-xL Expression[J].Cell Physiol Biochem,2018,45(3):1003-1012.
[5]肖小旺,文甲明,陈厚仰,等.Clusterin蛋白在男性不育症睾丸组织中的表达及意义[J].中国男科学杂志,2010,24(2):19-22.
[6]成克伦,李廷超,箭华勇,等.睾丸性不育症中Bim蛋白的表达[J].海南医学,2011,22(22):7-8.
[7]张卫星,秦俊昌,王瑞,等.D射线损伤对睾丸Claudin-11mRNA表达的影响[J].中华男科学杂志,2013,19(4):306-310.
[8]郝小燕,张金彪,王雪涛,等.严重少精子症和无精子症患者Y染色体微缺失和生殖激素水平分析[J].中国优生与遗传杂志,2017,25(10):49-50.
[9]陈小艳,陈平,徐畅,等.DAZL基因多态性位点(A260G、A386G)与无精子症和少精子症的关联性Meta分析[J].中华男科学杂志,2015,21(4):345-356.
[10]葛少钦,Jeanine Grifin,刘丽华,等.特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性[J].遗传,2013,35(5):616-622.
[11]王亚轩,常学良,瞿常宝,等.特发性少精子症生精细胞增殖与凋亡变化的研究[J].河北医科大学学报,2005,26(2):99-101.
[12]黄健红,黄乘,林飞鸿,等.少精子症患者性激素水平与生殖细胞凋亡的关系[J].广东医学,2008,29(5):771-772.
[13]Dubey SK,Hejtmancik JF,Krishnadas SR,et al.Evaluation of genetic polymorphisms in clusterin and tumor necrosis factoralpha genes in South Indian individuals with pseudoexfoliation synd-rome[J].Curr Eye Res,2015,40(12):1218-1224.
[14]Plotton I,Sanchez P,Durand P,et al.Decrease of both stem cell factor and clusterin mRNA levels in testicular biopsies of azoospermic patients with constitutive or idiopathic but not acquired spermatogenic failure[J].Hum Reprod,2006,21(9):2340-2345.
[15]Salehi M,Akbari H,Heidari MH,et al.Correlation between human clusterin in seminal plasma with sperm protamine deficiency and DNA fragmentation[J].Mol Reprod Dev,2013,80(9):718-724.
[16]Fukuda T,Miyake H,Enatsu N,et al.Seminal level of clusterin in infertile men as a significant biomarker reflecting spermatogenesis[J].Andrologia,2016,48(10):1188-1194.
[17]O'Bryan MK,Baker HW,Saunders JR,et al.Human seminal clusterin(SP-40,40).Isolation and characterization[J].J Clin Invest,1990,85(5):1477-1486.
[18]Grabow S,Kueh AJ,Ke F,et al.Subtle Changes in the Levels of Bcl-2 Proteins Cause Severe Craniofacial Abnormalities[J].Cell Rep,2018,24(12):3285-3295.
[19]Lin X,Shen J,Dan P,et al.RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells[J].Signal Transduct Target Ther,2018,31(3):23-29.
[20]Yue D,Sun X.Idelalisib promotes Bim-dependent apoptosis through AKT/Fox O3a in hepatocellular carcinoma[J].Cell Death Dis,2018,9(10):935-943.