知柏地黄丸对UU感染不育患者精子膜功能及uPA的影响
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摘要
目的:男性不育症影响着人类健康及家庭幸福,泌尿生殖道解脲脲原体(UU)感染和男性不育密切相关。目前,医学科研及临床工作者已经在用中医药治疗UU感染性不育症方面进行了有益的探索并取得了一些成果,但其机制有待深入研究。前期研究表明,知柏地黄丸能有效抑制UU生长;能下调生精细胞凋亡;具有抗感染和免疫调节功能。本研究在前期研究基础上,通过观察知柏地黄丸治疗UU感染性不育患者的临床疗效,观察精子膜功能完整性和uPA在用药前后的变化情况,探讨知柏地黄丸对UU感染不育患者精子膜功能和uPA的影响机制。
     方法:将合并UU感染的精子活力低下症不育患者130例,按就诊顺序随机分为知柏地黄丸治疗组(A组)72例与西药对照组(B组)58例。另选择同期就诊的无UU感染精子活力低下症不育患者50例,作为UU感染组治疗前的比较对象。中西药组均治疗3个月,治疗前后检测精液参数,精子膜功能完整性,顶体酶活性及uPA含量并作对比分析,观察临床疗效。
     结果:
     1.UU感染不育组精子活率、活力及正常形态精子百分率均低于非UU感染组(P<0.05),而两组精子密度比较没有明显差异(P>0.05)。A、B两组治疗后精子活率、活力及正常形态百分率比较差异有统计学意义(P<0.05),治疗后A组精子密度升高比B组明显,但两组密度比较无统计学意义(P>0.05)。
     2.UU感染不育组精子总膨胀率及G型精子膨胀率均较非UU感染不育组低,差异有统计学意义(P<0.05);A、B两组治疗后总膨胀率及G型精子膨胀率均提高,治疗组总膨胀率及G型精子膨胀率均优于对照组,差异有统计学意义(P<0.01)。
     3.UU感染不育组顶体酶活性及精子膜uPA含量均较非UU感染不育组低,差异有统计学意义(P<0.05);A、B两组治疗后精子顶体酶活性及uPA含量均明显提高,治疗后两组比较差异有统计学意义(P<0.01)。
     4.知柏地黄丸治疗组UU转阴率为87.5%,西药组UU转阴率为93.1%,两组无明显差异(P>0.05)。知柏地黄丸组治愈率25.71%,总有效率为88.57%,西药组治愈率为13.79%,总有效率为67.25%,两组治愈率和总有效率比较差异有统计学意义(P<0.01)
     结论:UU感染会破坏精子膜完整性,导致精子膜uPA含量降低;知柏地黄丸可以通过抑制UU生长,促进精子膜功能恢复并使精子膜uPA含量上升,提高精子的受精能力,有效治疗UU感染性不育症。
Objective Male infertility affects human health and well-being of families, genitourinary tract Ureaplasma urealyticum (UU) infection is closely related to male fertility. At present, medical researcher and clinical workers have made useful exploration in Chinese medicine for the treatment of UU infection in infertility, and achieved some results, but its mechanism needs further study. Previous studies have shown that, Zhibai Dihuang pill(ZBDHP) can effectively inhibit the growth of UU; can be reduced the apoptosis of spermatogenic cells; anti infection and immune regulation function. In this study, based on previous studies, through the observation of clinical curative effect of ZBDHP treatment of UU infection in infertility patients, to observe the functional integrity of sperm membrane and uPA changes in the situation before and after treatment, To explore the effect of ZBDHP on uPA and the Function of Sperm Membrane in Male Infertility patients with UU-infection.
     Methods30cases of male infertility patients with UU infection were randomly divided into2groups:treatment group of72cases (Group A) were given ZBDHP while control group of58cases (Group B) were given antibiotics.50infertility patients without UU infection were blank group to be compared with the UU infection groups. After3months of treatment, semen parameters, uPA and the functional integrity of sperm membrane were analyzed to observe the clinical efficacy.
     Results
     1. The sperm motility, viability and percentage of normal sperm morphology in UU infection groups were lower than those in non-UU infection group (P<0.05), but the sperm density had no significant differences between groups (P>0.05). After treatment, there were statistically significant differences between Group A and B in sperm viability, vigor and percentage normal morphology difference (P<0.05); the sperm density of Group A was higher than that of Group B but without statistical differences between2groups (P>0.05).
     2. The total rate of sperm expansion and G expansion rate in UU infection groups were lower than those of non-UU infection group; the differences were statistically significant (P<0.05). After treatment, the total expansion rate and G sperm expansion rate of Groups A and B were increased; the total rate of expansion and G expansion rate of sperm in Group A were better than in Group B with statistical difference (P<0.01).
     3. The acrosin activity and sperm membrane uPA content in UU infection groups were lower than those in non-UU infection group; the differences were statistically significant (P<0.05). The sperm acrosin activity and uPA content of Groups A and B were significantly improved after treatment; there was statistically significant difference between2groups (P<0.01).
     4. In ZBDHP group the cure rate was25.71%and the total efficiency was88.57%; in control group the cure rate was13.79%, and the total effective rate was67.25%; the differences between2groups were statistically significant (P<0.01).
     Conclusion UU infection can damage sperm membrane integrity, leading to decrease of sperm membrane uPA content; Zhibai Dihuang pill can eliminated UU, protect the function of sperm membrane and make the sperm membrane uPA content return to normal, so ZBDHP is effective in the treating UU infection in infertility..
引文
1. Dada R, upta NP, ucleherla K. Molecular screening for Yq mierodeletion in men with idiopathic oligozoospermia and azoospermia[J]. Biosci,2003,28(2):163-168.
    2. Gnarpe H, Friberg J. Mycoplasm a and hum -an reproductive failure. I. The occurrence of different Mycoplasm as in couples with reproductive failure [J]. Friberg Jam Job stet Gynecol,1972,114(6):727—731.
    3.郭航,郑海筝,王瑞雪,等.人精子膜功能完整性与精液参数的关系[J].基础医学与临床,2007,27(1):53-56.
    4.世界卫生组织编.谷栩群,陈振文,于和鸣,等译.人类精液及精子-宫颈粘液相互作用实验室检验手册[M].4版.北京:人民卫生出版社,2001:29.
    5.国家中医药管理局.中医病证诊断疗效标准[M].南京:南京大学出版社,1994.
    6. SFDA中药新药临床研究指导原则[M].北京:中国医药科技出版社,2002.
    7.Diemer T, Desjard C. Developmental and genetic disorders in spermatogenesis[J]. Hum Reprod Update,1999,5(1):120-125.
    8.姆巴亚,曾凡钦,陈宜芳.解脲支原体感染泌尿生殖器与射出精液细胞凋亡的关系研究[J].岭南皮肤性病科杂志,2000,7(4):1-3.
    9.Yi J, Yoon BH, Kim EC. Detection and biovar discrimination of Ureaplasma urealytieum by real—time PCR [J]. Mol Cell Probes,2005,19(4):255-260.
    10. McE lreavey K, et al.Y chromosome and male infertility:what is a normal Y chromosome [J]. J Soc Biol,2008,202 (2):135-141.
    11.谷诩群,董兆文,李银太,等.应用聚合酶链反应检测生殖道溶脲脲原体的研究[J].生殖医学杂志,1995,4(3):221.
    12. Sanocka-Maciejewska D, Ciupifiska M, Kurpisz M. Bacterialinfection and semen quality[J]. J Reprod Immunol,2005,67(1-2):51-56.
    13.Shimizu T, Kida Y, Kuwano K. Ureaplasma parvum lipoproteins, including MB antigen, activate NF-{kappa}B through TLR1, TLR2 and TLR6[J]. Microbiology,2008, 154(5):1318—1325.
    14.刘运科,郭彩娇,陈劲松等.解脲脲原体感染对男性不育症患者精液质量的影响[J].实用医学杂志,2001,17(2):116-117.
    15.聂尚丹、杨海霞、李雷生,等.男性不育患者解脲脲原体感染及对精液质量影响[J].济宁医学院学报,2009,32(6):408-409.
    16.蒋超,黄祝,魏杰等.解脲脲原体感染与精子DNA完整性的相关性的研究[J].生殖与避孕,2007,27(11):727-731.
    17. Reichart M, Kahane I, Bartoov B. In vivo and in vitro impairment of human and ram sperm nuclear chromatin integrity by sexually transmitted Ureaplasma urealyticum infection [J]. Biol Reprod,2000,63(4):1041-1048.
    18. Aziz N, Agarwal A, Lewis-Jones I, et al. Cryopreservation of human spermatozoa:comparison of two cryopreservation methods and three cryoprotectants [J]. Fertil Steril,2004,82(4):913-918.
    19.Xu C, LU MG, Feng JS, et al. Germ cell apoptosis inducedby Ureaplasma urealyticum infection[J]. Asian J Androl,2000,2(3):229-32.
    20.朱应武,卢芳国,伍参荣,等.解脲脲原体感染对精子质量的影响[J].实用预防医学,2003,10(6):931-933.
    21.张圣杰.男性解脲脲原体检测与男性不育患者的关系[J].吉林医学,2011,32(27):5643-5644.
    22.段红艳,章晓梅,任平.抗精子抗体对生育力影响的研究进展[J].2006,20(5):62-65.
    23. Reichart M, Levi H, Kahane I, et al. Dual energy metabolism dendent effect of Ureaplasma urealyticum infection on sperm activity[J]. Androl,2001,22(3): 404-412.
    24. Harl XD, Wang Y, Chen JX. A comparetive study on interrelations among microelements, infection of Ureaplasma urealyticum, and male infertility [J]. Arch Androl,2003,49(4):265-269.
    25.杨欣,王琦.溶脲脲原体感染与精液不液化症的相关性研究[J].中国男科学杂志,1998,12(4):222-224.
    26.白勇,李轩,张若愚,等.非细菌性前列腺炎与精子顶体酶活性的相关性及其在不育治疗中的意义[J].临床和实验医学杂志,2007,6(12):10-11.
    27.逯越,陈国卫.解脲脲原体感染对附睾上皮分泌功能影响的研究[J].解剖学研究,2003,25(4):277-278.
    28. Yassa DA, Idriss WK, Atassi ME, et al. The diagnostic value of seminal a-glucosidase enzyme index for sperm motility and fertilizing capacity[J]. Saudi Med J,2001,22(11):987—991.
    29.刘睿智,王忠山,韩淑梅,等.不育患者精浆a-1,4糖苷酶活性与精液参数的关系[J].生殖医学杂志2003,12(4):226-229.
    30. Cui Y H, Zhao R L, Wang Q, et al. Determination of sperm acrosin activity for evalu-ation of male fertility[J]. Asian J Androl,2000,2(3):229-32.
    31.Kodama L, Yam aguchi B, Fukuda J, et al. Increased oxidative deoxyribonucleic acid damage in the sperm atozoa of in fertile male patients[J]. Fertil Steril, 1997,68 (3):519-524.
    32.房磊臣,黄元华,李斌,等.解脲脲原体感染降低精子参数、精子膜功能及顶体酶活性[J].第三军医大学学报,2010,32(16):799-880.
    33.向丽,周铁军,王光西,等.解脲脲原体对人精子形态结构及顶体酶活性的影响[J].现代预防医学,2010,37(9):1735-1737.
    34.刘睿智,左文静沙艳伟,等.解脲支原体感染对精液主要参数和精子顶体酶活性的影响[J].中国优生与遗传杂志,2003,11(4):99-100.
    35.熊承良,吴明章,刘继红,等主编.人类精子学[M].武汉:湖北科学技术出社, 2002:182-189.
    36胡涛,王海燕,高美华,等.沙眼衣原体,溶脲脲原体感染致精浆TNF-A.IL-6升高在男性不育发病中的意义[J].生殖与避孕,1999,12(2):80-84.
    37.孙爱娣,陈开森,黎进,等.男性不育患者支原体感染与精浆IL-4, IFN-Y关系探讨[J].江西医学检验,2007,25(6):536-538.
    38. Kocak I, Yenisey C, Dundar M, Okyay P, Sert er M. Relationship between seminal plasma interleukin-6 and tumor necrosis factor alpha levels with semen parameters in fertile and infertile men[J]. Urol Res,2002,30:263-267.
    39.商学军.解脲支原体感染与生精细胞凋亡[J].男科学报,1999,5(1):21.
    40.岳林.精子膜完整性与精子功能评估的相关性研究[J].中国计划生育学杂志,2005(6):363-364.
    41.宋小青,刘继云,李继红,等.精子膜的完整性与男性不育的相关性研究[J].中国优生与遗传杂志,2008,16(9):110-111.
    42.王勇,韩晓冬,侯亚义,等.解脲脲原体感染与精液质量指标的相关性研究[J].南京大学学报,2001,37(2):228-131.
    43.石建莉,鲁梅格,王一飞,等.溶脲脲原体与人精子膜蛋白交叉反应抗原的研究[J].生殖与避孕,2003,23(3):153-156.
    44.冯耀,黄宇烽.解脲脲原体感染对精子膜功能的影响及机制的初步探讨[J].实用医学杂志,2009,25(18):3074-3076.
    45.徐志喜,李铁强,白慧玲,等.解脲支原体感染对精液及精子膜功能完整性的影响[J].第四军医大学学报,2003,24(2):129-131.
    46.黄勋彬,熊承良,夏文家,等.弱精症男子与正常人精子膜尿激酶型纤溶酶原激活因子含量的研究[J].男性学杂志,1997,11(2):83-85.
    47.熊承良,沈继云,周洁玲,等.尿激酶对弱精症患者精子活力影响的研究[J].生殖医学杂志,1995,4(3):164-166.
    48.15. Huarte J, Belin D, Bosco D, et al. Plasminogen activator and mouse sperm atozoa:urokinase synthesis in the male genital. tract and binding of the enzyme to the sperm cell surface [J]. J Cell Biol,1987,104(5):1281-1289.
    49.熊承良,黄勋彬,夏文家,等.人精子中尿激酶型纤溶酶原激活因子及其受体的分布[J].生殖与避孕,1996,16(6):422-424.
    50. Vihko KK, Penttila TL, Parvinen M, et al. Regulation of urokinase-and tissue-type plasminogen activator gene expression in the rat seminiferous epithelium[J]. Mol Endocrinol,1989,3(1).:52-59.
    51.Liu YX, Du Q, Liu K, et al. Hormonal regulation of plasminogen activator in rat and mouse'seminiferous epithelium [J]. Biol Signals,1995,4(4):232-240.
    52.郑萍,邹如金,刘以训.纤溶酶原激活因子与猕猴精子运动力的关系及其在附睾和附性腺中的表达调节[J].动物学研究,2002,23(1):19-24.
    53. Sitrin RG, Pan PM, Harper HA, et al. U rokinase receptor (CD87) aggregation triggers phosphoinositide hydrolysis andintracellular calcium mobilization in mononuclear phagocytes[J]. J Immunol,1999,163(11):6193-6200.
    54. Kim KS, Hong YK, Joe YA, et al. Anti—angiogenic activity of the recom binant kringle domain of urokinase and its specifie entry into endothelial cells[J]. J Biol Chem,2003,278(13):11449-11456.
    55. Vihko KK, Penttila TL, Parvinen M, et al. Regulation ofurokinase-and tissue-type plasminogen activator gene expression in the rat seminiferous epithelium[J]. Mol Endocrinol,1989,3(1):52-59.
    56. Liu YX, Du Q, Liu K, et al. Hormonal regulation of plas—minogen activator in rat and mouse seminiferous epithelium[J]. Biol Signals,1995,4(4):232—240.
    57.郑萍,邹如金,刘以训.猕猴精浆纤溶酶原激活因子的来源及在精子获能中的作用[J].生理学报,2001,53(1):45-50.
    58. Taitzoglou IA, Chapman DA, Killian GJ. Induction of theacrosome reaction in bull spermatozoa with plasmin[J]. Andrologia,2003,35(2):112—116.
    59.丁晓芳.尿激酶型纤溶酶原激活因子多环节促雄性生育作用及相关机制的实验研究.华中科技大学博士学位论文.2006,Ⅳ-Ⅷ.
    60.熊承良,夏文家,涂仁标,等.精液液化不良男子与正常人精浆尿激酶活性的研究.生殖医学杂志,1994,3(2):87-89.
    61.应俊,姚德洪.尿激酶治疗高黏稠度精液的临床研究.中国男科学杂志,2002,16(2):105-107.
    62.黄勋彬,熊承良,夏文家,等.弱精症男子与正常人精浆和精子膜尿激酶酶活性的研究[J].生殖医学杂志,1996,5(4):207-210.
    63.张奉梅,冯永堂.沙眼衣原体及解脉支原体感染对不育患者精浆sICAM-1及uPA的影响[J].中国免疫学会第五届全国代表大会暨学术会议论文集,333-334.
    64.胡海翔.解脲支原体与男性不育中医辨证关系的研究[J],中国中医基础医学杂志,1996,12(2):37-38.
    65.刘朝圣.知柏地黄汤对UU感染大鼠生精细胞凋亡及线粒体效应因子Caspase-3、 Caspase-9表达的影响.湖南中医药大学博士论文,2009,5.
    66.常改凤,马智超.深圳地区支原体对抗生素耐药性变迁的研究[J].实用预防医学,2003,10(1):7-9.
    67.孟小波.男性不育患者支原体感染检出率及药物敏感分析.医药论坛杂,2006,27(3):54-55
    68.曹玉璞,叶元康.支原体病与衣原体病[M].北京:人民卫生出版社,2000:87-105.
    69.刘忠义,张国威,何云志.解脲脲原体中药药敏试验.中华皮肤科杂志,1996,29(5):349.
    70.田正阳,丁原全,梁学林.中药抗解脲支原体的药敏试验.辽宁中医杂志,2009,36(6):998-999.
    71.沈黎明,喻林冲.解脲支原体对中药有效部位的药敏试验研究.华西药学杂志, 2012,27(3):294-295.
    72董文毅,金冶,李湛民,等.清毒衍宗散治疗解脲支原体性男性不育症38例临床观察.中医杂志,2007,48(6):518-520.
    73万卫民,肖洲南,崔幸琴,等.清精解尤汤治疗精液解脲支原体感染临床观察.中国性科学,2007,16(11):28-29
    74程军,金保方.清毒助育汤治疗解脲支原体致男性不育62例.中医研究,2005,18(12):28-30.
    75.郑佑军.消支护精散治疗解脲支原体感染性不育症的临床研究.中国中医药科技,2002,9(2):69-70.
    76.何清湖,李轩,张迅.知柏地黄汤加味治疗解脲脲原体前列腺炎50例.湖南中医杂志,2003,19(2):48.
    77..李轩.知柏地黄汤治疗解脲脲原体感染性前列腺炎及其提高精子活力的研究.湖南中医学院硕士论文,2003,5.
    78.张迅,何清湖,刘朝圣.知柏地黄汤对解脲脲原体感染大鼠动物模型生殖细胞凋亡及Fas、FasL表达的影响.湖南中医学院学报,2005,25(1):9-11.
    79.卢芳国,何清湖,张波,等.知柏地黄汤对解脲支原体感染大鼠睾丸组织IL-2及TNF-α表达水平的影响.中华中医药杂志,2011,26(3):448-450.
    [1]Shepard Mc Am J Syph[J].1954,38:113-114
    [2]Waites KB et al. Lancet [J].1988,1:17-21
    [3]Gnarpe H, Friberg J. T-mycoplasma as a possible cause for reproductive failure. Nature,1973,242:120
    [4]王勇,祝晓莹,李志军.解脲支原体和沙眼衣原体感染精液的影响.中华医院感染学杂志,2009,19(5):591-592.
    [5]黄静,沈尔明,应群华.精液解脲脲原体感染治疗前后精子质量的观察究.中国优生与遗传杂志,2006;10(6):108
    [6]刘运科,郭彩娇,陈劲松.解脲脲原体感染对男性不育症患者精液质量的影响.实用医学杂志,2001;17(2):116-117
    [7]商学军,徐建平,黄宇峰,等.精液解脲支原体感染与精子运动轨迹图象分析.男 性学杂志,1995:9(3):146
    [8]冯耀,黄宇峰.解脲脲原体感染对精子膜功能的影响及机制的初步探讨.实用医学杂志,2009;25(18):3074-3076
    [9]万长春,商学军,汪弘,等.解脲脲原体感染对精子功能影响的实验研究.临床检验杂志,1999;17(4):215-217
    [10]石建莉,鲁梅格,王一飞,等.溶脲脲原体与人精子膜蛋白交叉反应抗原的研究.生殖与避孕,2003;23(3):153-155
    [11]Reichart M, Kahane I, Bartoov B. Invivo and invitro impairment of human and ram sperm nuclear chromatin integrity by sexually transmitted Ureaplasma urealyticum infection [J]. Biol Reprod,2000,63(4):1041-1048
    [12]Audring H, et al. Ureaplasma Urealyticum and male infertility:an animal model[J].Andrologia,1989,21 (1):661
    [13]徐晨,徐胜,王一飞,等.解脲支原体引起男性不育机理研究(Ⅰ)—精子形态学观察.男性学杂志,1992,6(2):66
    [14]Engel, Baumann B. Des Von mycoplasmen in Hodengewebe Derm mschr.1989,165 (2):593-596
    [15]李宁丽,黄谷良.解脲脲原体细胞致病作用的研究.蚌埠医学院学报,1992;17(3):165-167
    [16]商学军.解脲支原体感染与生精细胞凋亡[J].男科学报,1999,5(1):21
    [17]胡涛,王海燕,高美华,等.沙眼衣原体、溶脲脲原体感染致精浆TNF-a、IL-6升高在男女不育发病中的意义.生殖与避孕.1999,19(2):80-84
    [18]张平,陈仰之,王家平,等.白细胞精子症病人精浆IL-8、CRP水平变化.中华男科学杂志,2001;7(3):193-194
    [19]Billig H, Furufa I, Rivier C, et al. Endocrinology,1995:136(1):5-15
    [20]马守中.精液解脲支原体感染的免疫荧光定位研究[J].男科学报,1998,4(1)12
    [21]查金智.男性生殖道解脲脲原体感染对精液的影响[J].男性学杂志,1997,11(1):13.
    [22]Aziz N, Agarwal A, Lewis-Jones I, et al. Cryopreservation of human spermatozoa:comparison of two cryopreservation methods and three cryoprotectants. Fertil Steril,2004,82(4):913-8
    [23]蒋超,黄祝,魏杰,等.解脲脲原体感染与精子DNA完整性的相关性的研究.生殖与避孕,2007,27(11):727-731
    [24]Xu C, LU MG, Feng JS, et al. Germ cell apoptosis induced by Ureaplasma urealyticum infection. Asian J Androl,2000,2(3):229-32
    [25]王勇,韩晓冬,侯亚义,等.解脲脲原体感染与精液质量指标的相关性研究[J].南京大学学报,2001,37(2):228-131
    [26]Potts JM, Sharma R, Pasqualotto F, et al. Urology.2000,63(6):1775~ 1778
    [27]Desil A, Patricia AQ. Clin microbiol.1991,29:1498
    [28]12.万卫民肖洲南崔幸琴,等.清精解尤汤治疗精液解脲支原体感染临床观察.中国性科学,2007,16(11):28-29.
    [29]彭少芳,杨志忠,林晓芬,等.消炎系列方治疗解脲支原体感染不育症精子形态的电镜观察[J].新中医,2004,36(2):19-20
    [30]朱章珍,梁金芝,冯洪.中药灌肠结合UBIO疗法治疗支原体感染男性不育疗效观察[J].中国临床医药研究杂志,2003,101:10463.
    [31]郑毅春,潘明沃,朱照平.滋阴清热法抑制解脲脲原体原染、提高精子活力的临床观察.中华中医药学刊.2013,31(1):83-84.

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