基于“HGF是乙癸同源物质基

发布时间：2018-03-19 09:50

本文选题：男性更年期综合征　切入点：HGF/c-Met　出处：《湖南中医药大学》2015年博士论文　论文类型：学位论文

【摘要】：[目的]1.了解长沙地区城镇男性居民的血清性激素随增龄变化规律,以及男性更年期综合征患病率；2.初步验证“HGF是乙癸同源物质基础”假说；3.探讨“肾肝同治法”干预男性更年期综合征的可能机制。 [方法]1.采用调查问卷形式,结合生化指标及性激素水平测定,logistic回归分析相关危险因素、保护因素；2.构建睾丸间质细胞-肝脏非实质细胞共培养体系,分别以含药血浆(雄蚕益肾疏肝方、金匮肾气丸、逍遥散)稀释0倍、4倍、8倍、16倍后干预,观察上清液中HGF.T含量,细胞中HGF.c-Met.caspase一3等指标；3.复制男性更年期综合征大鼠模型,随机分模型组、丙酸睾酮组、金匮组、逍遥组、雄蚕组,设立正常对照组,连续用药4周后,观察大鼠血清T.HGF,睾丸组织T合成酶(StAR.P450scc.3β-HSD)、HGF/c-Met.caspase一3等指标,HE染色观察睾丸组织形态学变化,电镜观察睾丸间质细胞超微结构。 [结果]1.长沙地区城镇男性居民血清TT.FT.Bio-T.FTI.SHBG水平,均随增龄出现梯度性变化,其中TT.FT.Bio-T.FTI与年龄、SG呈负相关；男性更年期综合征自我评定量表筛查阳性率为37.29%,男性更年期综合征临床总患病率为10.85%；年龄、体重指数、高血压病史、吸烟是男性更年期综合征发病的危险因素,每周有规律锻炼是其保护性因素。2.HGF/c-Met信号通路可能参与介导了睾丸间质细胞-肝脏非实质细胞共培养中睾丸间质细胞T分泌；雄蚕益肾疏肝方、金匮肾气丸、逍遥散含药血浆均能通过HGF/c-Met信号通路影响睾丸间质细胞T分泌,以雄蚕益肾疏肝方作用最强。3.男性更年期综合征大鼠模型睾丸间质细胞T合成能力下降,可能与以下机制有关：T合成酶(StAR.P450scc.3β-HSD)表达下调、HGF/c-Met表达下调、caspase一3表达上调,睾丸间质细胞凋亡增加；雄蚕益肾疏肝方、金匮肾气丸、逍遥散均能通过干预以上机制,增加T合成能力,其中以雄蚕益肾疏肝方作用最强,金匮肾气丸偏重于影响T合成酶活性,逍遥散偏重于影响HGF/c-Met信号通路 [结论]1.随着年龄增长,长沙地区城镇男性居民TT.FT.Bio-T水平下降,男性更年期综合征发病率较高,有规律的运动可有效预防。2.HGF/c-Met可能是联系中医肝、肾的关键物质基础。3.对男性更年期综合征的中医治疗,肾肝同治法优于单纯补肾法、疏肝法。
[Abstract]:[objective] 1. To understand the changes of serum sex hormones with age in urban male residents in Changsha area. And the prevalence rate of male climacteric syndrome 2.The hypothesis that "HGF is the homologous material basis of Edeca" was preliminarily verified. 3. To explore the possible mechanism of intervention of "kidney and liver simultaneous treatment" in male climacteric syndrome. [methods] 1. The risk factors were analyzed by logistic regression analysis in combination with biochemical indexes and sex hormone levels. 2. The co-culture system of testicular interstitial cells and liver non-parenchymal cells was constructed. Plasma containing medicine (male silkworm tonifying kidney and dispersing liver prescription, Jinkui Shenqi pills, Xiaoyao San) was used to dilute 0 times, 4 times, 8 times and 16 times, respectively, to observe the content of HGF.T in supernatant and HGF.c-Met.caspase-3 in cells. The male climacteric syndrome rat model was established. Model group, testosterone propionate group, Jinkui group, free group, male silkworm group were set up as normal control group. After 4 weeks of continuous administration, serum T. HGF, testicular tissue T synthase StAR.P450scc.3 尾 -HSDFc-Met.caspase-3 were stained to observe the morphological changes of testis. The ultrastructure of interstitial cells in testis was observed by electron microscope. [results] 1. The serum TT.FT.Bio-T.FTI.SHBG levels of urban male residents in Changsha area showed gradient changes with age, in which TT.FT.Bio-T.FTI was negatively correlated with age and SG; The positive rate of male climacteric syndrome self-rating scale was 37.29. The total clinical prevalence of male climacteric syndrome was 10.85. Age, body mass index, hypertension history, smoking were the risk factors of male menopausal syndrome. Weekly regular exercise is its protective factor. 2. HGF / c-Met signaling pathway may be involved in mediating T secretion of testicular interstitial cells in co-culture of non-parenchymal cells of the testis, male silkworm Yishen Shugan prescription, Jinkui Shenqi Pill, The plasma of Xiaoyao Powder can affect the T secretion of interstitial cells of testis through HGF/c-Met signal pathway, and the male silkworm Yishen Shugan recipe has the strongest effect. 3. The T synthesis ability of testis interstitial cells in male climacteric syndrome rats is decreased. It may be related to the following mechanisms: the down-regulation of T: synthase StAR.P450scc.3 尾 -HSD-expression and down-regulation of the expression of HGFc-Met up-regulate the expression of caspase-3 and increase the apoptosis of testicular interstitial cells; the male silkworm Yishen Shugan prescription, Jinguishen Qi Pill and Xiaoyao Powder can all intervene through the above mechanisms. Increase the ability of T synthesis, in which male silkworm Yishen Shugan prescription has the strongest effect, Jingui Shenqi Pill focuses on the influence of T synthase activity, and Xiaoyao Powder focuses on affecting HGF/c-Met signal pathway. [conclusion] 1. With the increase of age, the level of TT.FT.Bio-T in urban male residents in Changsha area decreased, and the incidence of male climacteric syndrome was higher. The regular exercise can effectively prevent. 2. HGF / c-Met may be associated with traditional Chinese medicine liver. The treatment of male climacteric syndrome by traditional Chinese medicine is superior to the simple method of tonifying the kidney and soothing the liver.
【学位授予单位】：湖南中医药大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R697.22

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