阴茎海绵体平滑肌细胞表型转化和勃起功能障碍的相关研究进展
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摘要
勃起功能障碍(ED)与阴茎海绵体平滑肌细胞(CCSMC)表型转化密切相关。CCSMC表型转化表现为一种CCSMC由"收缩型"向"合成型"或"增殖型"改变的趋势,α平滑肌肌动蛋白(α-SMA)、平滑肌肌球蛋白重链(SMMHC)、碱性调宁蛋白、肌滑蛋白、肌间线蛋白等可作为收缩型CCSMC分子标志物,波形蛋白、骨桥蛋白、I型胶原蛋白等可作为合成型或增殖型CCSMC分子标志物。目前,以CCSMC表型转化作为切入点进行研究相对较多的是双侧海绵体神经损伤所致的神经源性ED和糖尿病性ED,亦可见动脉性ED、高血压性ED的少许报道;另外,缺氧、血小板源性生长因子、烟草燃烧气体等外界因素直接作用于大鼠或CCSMC时亦会导致CCSMC表型转化。本文将根据目前的研究报道,对CCSMC表型转化与ED相关研究进行系统回顾。
Erectile dysfunction( ED) is closely related with the phenotypic modulation of corporal cavernosum smooth muscle cells( CCSMC),a transitional tendency of CCSMCs switching from the contractile phenotype to the synthetic or proliferative phenotype. The molecular markers of contractile CCSMCs include α-SMA,SMMHC,Calponin,Smoothelin,and Desmin,while those of synthetic or proliferative CCSMCs involve Vimentin,Osteopontin,and Collagen I. Current studies show that phenotypic transformation of CCSMCs is related to the pathophysiological processes of different types of ED,such as bilateral cavernous nerve injury-induced ED,diabetes mellitus-associated ED,arterial ED,hypertension-associated ED,and so on. In addition,such external factors as hypoxia,platelet-derived growth factor,and tobacco combustion gas may directly affect rats or CCSMCs and consequently lead to phenotypic conversion of CCSMCs. This article presents a systematic review of the studies on the correlation of phenotypic transition of CCSMCs with ED.
Erectile dysfunction( ED) is closely related with the phenotypic modulation of corporal cavernosum smooth muscle cells( CCSMC),a transitional tendency of CCSMCs switching from the contractile phenotype to the synthetic or proliferative phenotype. The molecular markers of contractile CCSMCs include α-SMA,SMMHC,Calponin,Smoothelin,and Desmin,while those of synthetic or proliferative CCSMCs involve Vimentin,Osteopontin,and Collagen I. Current studies show that phenotypic transformation of CCSMCs is related to the pathophysiological processes of different types of ED,such as bilateral cavernous nerve injury-induced ED,diabetes mellitus-associated ED,arterial ED,hypertension-associated ED,and so on. In addition,such external factors as hypoxia,platelet-derived growth factor,and tobacco combustion gas may directly affect rats or CCSMCs and consequently lead to phenotypic conversion of CCSMCs. This article presents a systematic review of the studies on the correlation of phenotypic transition of CCSMCs with ED.
引文
[1] Zhang X,Yang B,Li N,et al. Prevalence and risk factors for erectile dysfunction in Chinese adult males. J Sex Med,2017,14(10):1201-1208.
[2]邓吉坤,谭艳.缺氧性ED模型阴茎海绵体微结构改变的研究进展.中华男科学杂志,2016,22(10):932-937.
[3]邓吉坤,谭艳.缺氧条件下自噬导致CCSMC表型转化机制的研究进展.中华男科学杂志,2016,22(11):1025-1029.
[4]刘文彬,张海波,王涛,等. Myocardin基因与勃起功能障碍相关的研究进展.中国男科学杂志,2017,31(1):65-68.
[5]陈建国,姜睿.平滑肌收缩机制及其与勃起功能障碍的关系.中华男科学杂志,2018,24(2):172-175.
[6] Owens GK,Kumar MS,Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev,2004,84(3):767-801.
[7] Beamish JA,He P,Kottke-Marchant K,et al. Molecular regulation of contractile smooth muscle cell phenotype:Implications for vascular tissue engineering. Tissue Eng Part B Rev,2010,16(5):467-491.
[8] Yafi FA,Jenkins L,Albersen M,et al. Erectile dysfunction.Nat Rev Dis Primers. 2016,2:16003.
[9] Weyne E,Mulhall J,Albersen M. Molecular pathophysiology of cavernous nerve injury and identification of strategies for nervefunction recovery after radical prostatectomy. Curr Drug Targets,2015,16(5):459-473.
[10] Yang F,Zhao JF,Shou QY,et al. Phenotypic modulation of corpus cavernosum smoothmuscle cells in a rat model of cavernous neurectomy. PLo S One,2014,9(8):e105186.
[11]刘山山,吕伯东,赵剑锋,等.缺氧对SD大鼠阴茎海绵体平滑肌细胞表型转化的影响.浙江中医药大学学报,2013,37(7):897-901.
[12] Lv B,Zhao J,Yang F,et al. Phenotypic transition of corpus cavernosum smooth muscle cells subjected to hypoxia. Cell Tissue Res,2014,357(3):823-833.
[13] Zhang X,Zhao JF,Zhao F,et al. The protective effect of salidroside on hypoxia-induced corpus cavernosum smooth muscle cell phenotypic transformation. Evid Based Complement Alternat Med,2017,2017:3530281.
[14] Yan JF,Huang WJ,Zhao JF,et al. The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypictransition of corpus cavernosum smooth muscle in rats. PLo S One,2017,12(2):e0172191.
[15] Zhang X,Zhao F,Zhao JF,et al. PDGF-mediated PI3K/AKT/β-catenin signaling regulates gap junctions in corpus cavernosum smooth muscle cells. Exp Cell Res,2018,362(2):252-259.
[16]罗金泰,余文俊,韦安阳,等.血小板源性生长因子-BB对SD大鼠阴茎海绵体平滑肌细胞表型转化影响的初步研究.中华男科学杂志,2015,21(7):593-597.
[17]陈逢志,何书华,单海涛,等.血小板源性生长因子-BB对大鼠阴茎海绵体平滑肌细胞增殖、迁移及表型转化的影响.南方医科大学学报,2015,35(7):971-976.
[18] Zhang HB,Wang ZQ,Chen FZ,et al. Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats. Andrology,2017,5(4):798-806.
[19] Castela,Costa C. Molecular mechanisms associated with diabetic endothelial erectile dysfunction. Nat Rev Urol,2016,13(5):266-274.
[20] Sullivan CJ,Teal TH,Luttrell IP,et al. Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats. Physiol Genomics,2005,23(2):192-205.
[21] He SH,Wei AY,Yang Y,et al. Reduced expression of myocardin and serum responsefactor in the cavernous tissue of diabetic rats. Andrologia,2012,44(Suppl 1):518-522.
[22] Wei AY,He SH,Zhao JF,et al. Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction. Int J Impot Res,2012,24(5):196-201.
[23] He S,Zhang T,Liu Y,et al. Myocardin restores erectile function in diabetic rats:Phenotypic modulation of corpus cavernosum smooth muscle cells. Andrologia,2014,47(3):303-309.
[24] Zhang X,Kanika ND,Melman A,et al. Smooth muscle myosin expression,isoform composition,and functional activities in rat corpus cavernosum altered by the streptozotocin-induced type 1diabetes. Am J Physiol Endocrinol Metab,2012,302(1):E32-E42.
[25]何书华,韦安阳,叶挺宇,等.降钙素基因相关肽对糖尿病性ED大鼠阴茎海绵体平滑肌细胞表型转化的影响.中华男科学杂志,2011,17(10):913-917.
[26]杨勇,胡存利,邱海峰.内皮素-1在糖尿病性勃起功能障碍大鼠阴茎海绵体平滑肌细胞表型转化中作用.中华实用诊断与治疗杂志,2014,28(6):559-561.
[27]李煜罡,潘恩山,朱晓光.益肾活血汤对糖尿病性ED大鼠阴茎海绵体平滑肌细胞calponin 1和OPN表达的影响.中国男科学杂志,2013,27(6):13-18.
[28]张硕.五味子醇甲对糖尿病勃起功能障碍大鼠勃起功能及平滑肌细胞表型转化蛋白影响的研究(硕士论文).石家庄:河北医科大学,2017.
[29]崔莉.复方玄驹胶囊对ED大鼠CCSMC中H1CaP、OPN、TGF-β1及超微结构的影响研究(硕士论文).成都:成都中医药大学,2013.
[30]于军桥,曾政光,周仕轶,等.中药益坎胶囊对动脉性勃起功能障碍大鼠阴茎海绵体平滑肌细胞表型转化的影响.中华男科学杂志,2014,20(10):916-921.
[31]韦安阳,吴威武,吴浩彬,等.高血压大鼠阴茎海绵体平滑肌细胞表型转化.南方医科大学学报,2009,29(5):925-928.
[32]程祎,韦安阳,吴威武,等.硒对高血压勃起功能障碍大鼠阴茎海绵体平滑肌表型逆转化的影响.实用医学杂志,2015,31(11):1738-1740.
[33] Liu L,Li E,Li F,et al. Effect of testosterone on the phenotypic modulation of corpus cavernosum smooth muscle cells in a castrated rat model. Urology,2017,103:273. e1-273. e6.
[34]黄晓军,吕伯东,陈刚.红景I号方对低氧大鼠阴茎海绵体平滑肌细胞表型转化的影响.中华中医药学刊,2012,30(9):2027-2029.
[35]陈逢志.血小板源性生长因子BB下调myocardin在低氧诱导的大鼠阴茎海绵体平滑肌细胞表型转化中的作用(硕士论文).广州:南方医科大学,2015.
[36]韦安阳,杨勇,何书华,等. miR-145在糖尿病性勃起功能障碍大鼠发病机制中的作用.南方医科大学学报,2011,31(6):1051-1054.
[37] Luo J,Liu L,Wu Z,et al. The effects of miRNA-145 on the phenotypic modulation of rat corpus cavernosum smooth muscle cells. Int J Impot Res,2017,29(6):229-234.
[38] Verze P,Margreiter M,Esposito K,et al. The link between cigarette smoking and erectile dysfunction:A systematic review. Eur Urol Focus,2015,1(1):39-46.
[39]程祎,吴威武,李杰,等.吸烟大鼠阴茎海绵体平滑肌表型转化的研究.齐齐哈尔医学院学报,2015,36(15):2187-2188.
[2]邓吉坤,谭艳.缺氧性ED模型阴茎海绵体微结构改变的研究进展.中华男科学杂志,2016,22(10):932-937.
[3]邓吉坤,谭艳.缺氧条件下自噬导致CCSMC表型转化机制的研究进展.中华男科学杂志,2016,22(11):1025-1029.
[4]刘文彬,张海波,王涛,等. Myocardin基因与勃起功能障碍相关的研究进展.中国男科学杂志,2017,31(1):65-68.
[5]陈建国,姜睿.平滑肌收缩机制及其与勃起功能障碍的关系.中华男科学杂志,2018,24(2):172-175.
[6] Owens GK,Kumar MS,Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev,2004,84(3):767-801.
[7] Beamish JA,He P,Kottke-Marchant K,et al. Molecular regulation of contractile smooth muscle cell phenotype:Implications for vascular tissue engineering. Tissue Eng Part B Rev,2010,16(5):467-491.
[8] Yafi FA,Jenkins L,Albersen M,et al. Erectile dysfunction.Nat Rev Dis Primers. 2016,2:16003.
[9] Weyne E,Mulhall J,Albersen M. Molecular pathophysiology of cavernous nerve injury and identification of strategies for nervefunction recovery after radical prostatectomy. Curr Drug Targets,2015,16(5):459-473.
[10] Yang F,Zhao JF,Shou QY,et al. Phenotypic modulation of corpus cavernosum smoothmuscle cells in a rat model of cavernous neurectomy. PLo S One,2014,9(8):e105186.
[11]刘山山,吕伯东,赵剑锋,等.缺氧对SD大鼠阴茎海绵体平滑肌细胞表型转化的影响.浙江中医药大学学报,2013,37(7):897-901.
[12] Lv B,Zhao J,Yang F,et al. Phenotypic transition of corpus cavernosum smooth muscle cells subjected to hypoxia. Cell Tissue Res,2014,357(3):823-833.
[13] Zhang X,Zhao JF,Zhao F,et al. The protective effect of salidroside on hypoxia-induced corpus cavernosum smooth muscle cell phenotypic transformation. Evid Based Complement Alternat Med,2017,2017:3530281.
[14] Yan JF,Huang WJ,Zhao JF,et al. The platelet-derived growth factor receptor/STAT3 signaling pathway regulates the phenotypictransition of corpus cavernosum smooth muscle in rats. PLo S One,2017,12(2):e0172191.
[15] Zhang X,Zhao F,Zhao JF,et al. PDGF-mediated PI3K/AKT/β-catenin signaling regulates gap junctions in corpus cavernosum smooth muscle cells. Exp Cell Res,2018,362(2):252-259.
[16]罗金泰,余文俊,韦安阳,等.血小板源性生长因子-BB对SD大鼠阴茎海绵体平滑肌细胞表型转化影响的初步研究.中华男科学杂志,2015,21(7):593-597.
[17]陈逢志,何书华,单海涛,等.血小板源性生长因子-BB对大鼠阴茎海绵体平滑肌细胞增殖、迁移及表型转化的影响.南方医科大学学报,2015,35(7):971-976.
[18] Zhang HB,Wang ZQ,Chen FZ,et al. Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats. Andrology,2017,5(4):798-806.
[19] Castela,Costa C. Molecular mechanisms associated with diabetic endothelial erectile dysfunction. Nat Rev Urol,2016,13(5):266-274.
[20] Sullivan CJ,Teal TH,Luttrell IP,et al. Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats. Physiol Genomics,2005,23(2):192-205.
[21] He SH,Wei AY,Yang Y,et al. Reduced expression of myocardin and serum responsefactor in the cavernous tissue of diabetic rats. Andrologia,2012,44(Suppl 1):518-522.
[22] Wei AY,He SH,Zhao JF,et al. Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction. Int J Impot Res,2012,24(5):196-201.
[23] He S,Zhang T,Liu Y,et al. Myocardin restores erectile function in diabetic rats:Phenotypic modulation of corpus cavernosum smooth muscle cells. Andrologia,2014,47(3):303-309.
[24] Zhang X,Kanika ND,Melman A,et al. Smooth muscle myosin expression,isoform composition,and functional activities in rat corpus cavernosum altered by the streptozotocin-induced type 1diabetes. Am J Physiol Endocrinol Metab,2012,302(1):E32-E42.
[25]何书华,韦安阳,叶挺宇,等.降钙素基因相关肽对糖尿病性ED大鼠阴茎海绵体平滑肌细胞表型转化的影响.中华男科学杂志,2011,17(10):913-917.
[26]杨勇,胡存利,邱海峰.内皮素-1在糖尿病性勃起功能障碍大鼠阴茎海绵体平滑肌细胞表型转化中作用.中华实用诊断与治疗杂志,2014,28(6):559-561.
[27]李煜罡,潘恩山,朱晓光.益肾活血汤对糖尿病性ED大鼠阴茎海绵体平滑肌细胞calponin 1和OPN表达的影响.中国男科学杂志,2013,27(6):13-18.
[28]张硕.五味子醇甲对糖尿病勃起功能障碍大鼠勃起功能及平滑肌细胞表型转化蛋白影响的研究(硕士论文).石家庄:河北医科大学,2017.
[29]崔莉.复方玄驹胶囊对ED大鼠CCSMC中H1CaP、OPN、TGF-β1及超微结构的影响研究(硕士论文).成都:成都中医药大学,2013.
[30]于军桥,曾政光,周仕轶,等.中药益坎胶囊对动脉性勃起功能障碍大鼠阴茎海绵体平滑肌细胞表型转化的影响.中华男科学杂志,2014,20(10):916-921.
[31]韦安阳,吴威武,吴浩彬,等.高血压大鼠阴茎海绵体平滑肌细胞表型转化.南方医科大学学报,2009,29(5):925-928.
[32]程祎,韦安阳,吴威武,等.硒对高血压勃起功能障碍大鼠阴茎海绵体平滑肌表型逆转化的影响.实用医学杂志,2015,31(11):1738-1740.
[33] Liu L,Li E,Li F,et al. Effect of testosterone on the phenotypic modulation of corpus cavernosum smooth muscle cells in a castrated rat model. Urology,2017,103:273. e1-273. e6.
[34]黄晓军,吕伯东,陈刚.红景I号方对低氧大鼠阴茎海绵体平滑肌细胞表型转化的影响.中华中医药学刊,2012,30(9):2027-2029.
[35]陈逢志.血小板源性生长因子BB下调myocardin在低氧诱导的大鼠阴茎海绵体平滑肌细胞表型转化中的作用(硕士论文).广州:南方医科大学,2015.
[36]韦安阳,杨勇,何书华,等. miR-145在糖尿病性勃起功能障碍大鼠发病机制中的作用.南方医科大学学报,2011,31(6):1051-1054.
[37] Luo J,Liu L,Wu Z,et al. The effects of miRNA-145 on the phenotypic modulation of rat corpus cavernosum smooth muscle cells. Int J Impot Res,2017,29(6):229-234.
[38] Verze P,Margreiter M,Esposito K,et al. The link between cigarette smoking and erectile dysfunction:A systematic review. Eur Urol Focus,2015,1(1):39-46.
[39]程祎,吴威武,李杰,等.吸烟大鼠阴茎海绵体平滑肌表型转化的研究.齐齐哈尔医学院学报,2015,36(15):2187-2188.