Survey for late-onset hypogonadism among old anti middle-aged males in Shanghai communities

This study sought to investigate late-onset hypogonadism （LOH） in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms （AMS） scale and androgen deficiency in aging males （ADAM） questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors （total testosterone （TT）, free testosterone （fT）, sex hormone-binding globulin （SHBG） and bioavailability of testosterone （Bio-T））. There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results： TT was not related to aging （P〉O.05）; levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.

How to recognize late-onset hypogonadism in men wit sexual dysfunction

Late-onset hypogonadism （LOH） has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone （T） levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T （different thresholds）, sexual parameters, medical history data （delayed puberty, pituitary disease or cryptorchidism） and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.

Erectile function and late-onset hypogonadism symptoms related to lower urinary tract symptom severity in elderly men

The aim of this study was to evaluate the relationship between lower urinary tract symptoms （LUTSs）, erectile dysfunction （ED） and symptomatic late-onset hypogonadism （SLOH） in ageing men in the Aegean region of Turkey. Five hundred consecutive patients 〉40 years old who had been in a steady sexual relationship for the past 6 months and were admitted to one of six urology clinics were included in the study. Serum prostate-specific antigen and testosterone levels and urinary flow rates were measured. All patients filled out the International Prostate Symptom Score and Quality of Life （IPSS-QoL）, International Index of Erectile Function （IIEF） and Aging Males＇ Symptoms （AMS） scale forms. Of the patients, 23.9% had mild LUTSs, 53.3% had moderate LUTSs and 22.8% had severe LUTSs. The total testosterone level did not differ between groups. Additionally, 69.6% had ED. The presence of impotence increased with increasing LUTS severity. Symptomatic late-onset hypogonadism （AMS 〉27） was observed in 71.2% of the patients. The prevalence of severe hypogonadism symptoms increased with the IPSS scores. A correlation analysis revealed that all three questionnaire scores were significantly correlated. In conclusion, LUTS severity is an age-independent risk factor for ED and SLOH. LUTS severity and SLOH symptoms appear to have a strong link that requires etiological and biological clarification in future studies.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators （SARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

Surveys of serum reproductive hormone levels and the prevalence rates of late onset of hypogonadism in Chinese aging males

Objective:To investigate the change patterns of reproductive hormones in serum of aging males and the difference among male age brackets and the prevalence rates of late onset of hypogonadism(LOH) in males in Chinese middle and aging males. Methods:Subjects included 1,498 men aged 40 to 69 from a county,and the serum reproductive hormones of 434 subjects were measured and calculated.In addition,the prevalence rates of LOH were analyzed by cut-off point of total testosterone(TT) and free testosterone(cFT),and screening scales(a questionnaire of androgen deficiency in the aging males(ADAM) and a scale of aging males’ symptoms(AMS)).TT,cFT,bio-available testosterone (Bio-T),luteinizing hormone(LH),sex hormone binding globulin(SHBG),testosterone secretion index(TSI), free testosterone index(FTD,the positive rates of LOH screening,androgen deficiency rates and the clinical prevalence rates of LOH were measured or calculated. Results:The serum TT levels did not change significantly with male aging while serum LH and SHBG levels gradually increased,but cFT,Bio-T,TSI and FTI levels gradually decreased with male aging.There was very significant difference in other six parameters of reproductive hormones(P<0.01),except for serum TT among the four age brackets(P>0.05).There was no correlation between serum TT levels and aging,LH levels(P>0.05). However,there was significantly a positive correlation between serum LH,SHBG and age(P<0.01),while there were negative correlation between cFT,Bio-T,TSI,FTI and age,LH levels(P<0.01).Moreover,SHBG level was positively correlated with LH level(P<0.01). Utilizing the Questionnaire of ADAM and AMS to screen subjects aged 40 to 69 years,mean positive rates of LOH screening were 80.77%and 32.34%respectively.Mean androgen deficiency rates were 14.02%and 43.69% by using TT and cFT cut-off point.In addition,mean LOH clinical prevalence rates of subjects on positive questionnaire results were 37.85%and 15.42%. Conclusion:The serum TT levels did not change significantly with male aging while serum LH,SHBG,cFT, Bio-T,TSI and FTI levels had the gradient change with aging.On the basis of Chinese population,however,the positive rate of LOH screening,androgen deficiency rate and clinical prevalence rate of LOH were obviously higher than that those of the other foreign studies.

Hypogonadism and erectile dysfunction： an overview

In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capasity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintanence of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases （eNOS and nNOS）, and phosphodiesterase type-5 （PDE-5）, which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintanence of penile tissue and erectile physiology as well. Furhermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalance, diagnosis and treatment options of hypogonadism in aging men.

restosterone replacement therapy for late-onsel lypogonadism： current trends in Korea

Testosterone levels in men older than 40 years can decrease at a rate of 1%-2% per year, and reports show that more than 50% of 80-year-old men have testosterone levels consistent with hypogonadism. Late-onset hypogonadism （LOH） is a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms of serum testosterone deficiency. In recent decades, the concept of LOH in ageing men has become familiar in European countries and the United States. It is also a topic of interest and debate throughout Korea. However, most of the data regarding advantages or disadvantages of testosterone replacement therapy （TRT） as treatment for LOH have been primarily obtained from studies on Western populations; therefore, studies of the effects of TRT in Asian men, who may have different serum testosterone compared to Western men, are needed. TRT is commonly prescribed in Korea, despite the paucity of studies on the effects of TRT in Asian populations. Data from various TRT studies based on Korean have shown its efficacy in increasing serum testosterone levels and improving subjective symptoms as assessed by questionnaires. Currently, patches and short-acting intramuscular injections are displaced by gels and long-acting formulations. However, to prevent overdiagnosis and overtreatment, indication for TRT should include both low testosterone levels and symptoms and signs of hypogonadism.

从“天癸-肝肾”论治男性迟发性性腺功能减退症

男性迟发性性腺功能减退症(late onset hypogonadism, LOH)临床症状多样,影响广泛,患病率较高,对中老年男性身心健康危害重大。基于天癸理论,从中医视角辨治LOH具有重要临床价值。天癸源于肾精,受肝脏疏泄而发挥正常功能,天癸竭、肾虚、肝郁三者相互作用共同导致LOH发病。在此过程中,“天癸渐竭”是LOH发病的根本因素;“肾虚肝郁”是LOH发病的主要因素,其中,“肾虚”导致天癸化生乏源而亏虚更甚;“肝郁”则导致天癸疏泄失司而功能失调。“天癸渐竭、肾虚肝郁”构成LOH发病的中医核心病机,因此,治疗上强调未病调天癸,既病调肝肾,以期为LOH的论治提供新思路。

基于“脑-心-肾-精室轴”理论治疗迟发性性腺功能减退症的用药分析

迟发性性腺功能减退症(LOH)是中老年男性的一种常见疾病,可伴随多方面的症状,对患者生活质量有较大影响。“脑-心-肾-精室轴”理论是一种新的中医理论,可解释LOH的发病机制,为LOH的诊断与治疗提供了新的角度,达到身心同调、形神同治的目的。本文基于“脑-心-肾-精室轴”理论对治疗LOH的药物进行了简要的梳理与介绍。

Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population

Background Late onset hypogonadism negatively impacts on men＇s psychological well-being This study was conducted to examine the interrelationship among symptoms of testosterone deficiency, psychological well-being, and quality of life.Methods Eligible subjects were randomized into active treatment and control groups, and were asked to complete the following questionnaires at baseline and month 6： aging male＇s symptoms （AMS） rating scale,

Late-onset hypogonadism： beyond testosterone

Late-onset hypogonadism is defined as a combination of low testosterone （T） levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell （dys）function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone （LH） and 25-hydroxyvitamin D levels. These markers help in identifying the so-called ＂subclinical＂ hypogonadism （normal T, high LH levels）. Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option （cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D） in these patients. We studied 66 patients with classic hypogonadism （total T [TT] 〈12 nmol I-~, LH 〉 8 IU 1-1） （n = 26） and subclinical hypogonadism （TT 〉 12 nmol I-＊, LH 〉 8 IU I-~） （n = 40） and low 25-hydroxyvitamin D （〈50 nmol I-1）. Subjects received cholecalciferol （5000 IU per week） （n = 20） or calcidiol （4000 IU per week） （n -- 46）, and 25-hydroxyvitamin D and parathyroid hormone （PTH） were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PI＂H levels in both groups of men with hypogonadism （primary, n = 16 and subclinical, n = 30）, whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D （calcidiol）, and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.

Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism： a multicenter, randomized controlled trial in Japan （EARTH Study）

Androgen replacement therapy （ART） efficacy on late-onset hypogonadism （LOH） has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores （IPSS）, International Index of Erectile Function-5 （IIEF-5） scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART （n = 169） or control groups （n = 165）. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey （SF-36） scale （P= 0.0318）. ART was also associated with significant decreases in waist circumstance （P = 0.002） and serum triglyceride （TG） （P = 0.013） and with significant increases in whole-body and leg muscle mass volumes （P= 0.071 and 0.0108, respectively）, serum hemoglobin （P 〈 0.001）, IPSS voiding subscore （P = 0.0418）, and the second question on I IEF-5 （P = 0.0049）. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.

雄蚕益肾方对LOH大鼠Leydig细胞胆固醇转运蛋白、睾酮合成酶和SF-1表达的影响

目的:探讨雄蚕益肾方对LOH大鼠Leydig细胞胆固醇转运蛋白、睾酮合成酶和SF-1表达的影响。方法:25只18月龄雄性SD大鼠随机均分为模型组、丙酸睾酮组、雄蚕益肾方-低、中、高剂量组,2月龄雄性SD大鼠5只设为正常组。雄蚕益肾方-低、中、高剂量组分别给予10.4、20.8、41.6 g/(kg·d)体重剂量的雄蚕益肾方配方颗粒剂灌胃;丙酸睾酮组大鼠肌注5.21 mg/(kg·d).体重剂量的丙酸睾酮,每周3次;正常组和模型组给予相同体积的蒸馏水灌胃,均连续28 d。实验结束后取睾丸组织进行Western印迹检测StAR、TSPO、CYP11A1、HSD3B7、HSD17B4和SF-1蛋白表达。结果:模型组大鼠睾丸组织StAR、TSPO、CYP11A1、HSD3B7、HSD17B4蛋白和SF-1表达均显著低于正常组(P<0.05);与模型组相比,雄蚕益肾方-低、中、高各剂量组大鼠睾丸组织StAR、TSPO、CYP11A1、HSD3B7、HSD17B4蛋白和SF-1显著增高(P<0.05)。结论:雄蚕益肾方能上调LOH大鼠睾丸组织胆固醇转运蛋白(StAR、TSPO)、睾酮合成酶(CYP11A1、HSD3B7、HSD17B4)以及上游转录因子SF-1表达水平,可能是其干预LOH的机制之一。

雄蚕益肾方对小鼠睾丸间质细胞氧化应激损伤后铁死亡的影响

目的:探讨雄蚕益肾方含药血清对H2O2诱导小鼠睾丸间质细胞氧化应激损伤后铁死亡的影响。方法:应用H2O2诱导小鼠TM3睾丸间质细胞建立氧化应激损伤模型,将诱导成模的TM3细胞随机分为模型组、雄蚕益肾方组、铁死亡抑制剂Ferrostatin-1组、Ferrostatin-1联合雄蚕益肾方组,分别用空白血清、20%含药血清、2μmol/L Ferrostatin-1、2μmol/L Ferrostatin-1+20%含药血清干预,另设置对照组(正常TM3细胞+空白血清)。观察各组细胞形态,检测各组细胞分泌的睾酮、超氧化物歧化酶(SOD)、活性氧(ROS)、丙二醛(MDA)、铁蛋白重链1(FTH1)、溶质载体家族7成员11(SLC7A11)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶4(GPX4)、脂肪酸辅酶A连接酶4(FACL4)、总铁离子及亚铁离子含量。结果:与模型组比较,对照组ROS、MDA、FACL4、总铁和亚铁离子表达均显著降低(P<0.05),睾酮、SOD、谷胱甘肽、FTH1、SLC7A11及GPX4表达均显著升高(P<0.05);雄蚕益肾方组能显著促进TM3细胞分泌睾酮并上调TM3细胞FTH1、SLC7A11、GPX4、GSH和SOD表达(P<0.05),显著下调ROS、MDA、FACL4、总铁离子和亚铁离子表达(P<0.05)。结论:H2O2暴露后可通过氧化应激诱导小鼠TM3睾丸间质细胞发生铁死亡,雄蚕益肾方可能通过激活SLC7A11/GSH/GPX4轴拮抗TM3细胞氧化应激损伤及铁死亡,这可能是雄蚕益肾方治疗男性迟发性性腺功能减退症的潜在作用机制。

血清25-羟基维生素D及骨钙素水平与老年2型糖尿病合并迟发性性腺功能减退症的关系

目的研究血清25-羟基维生素D[25-hydroxyvitaminD,25(OH)D]及骨钙素(Osteocalcin,OC)水平与老年2型糖尿病(Type 2 diabetes mellitus,T2DM)合并迟发性性腺功能减退症(Late-onset hypogonadism,LOH)的关系。方法以2018年5月—2021年5月新疆医科大学第一附属医院内分泌科收治的120例老年T2DM合并LOH患者为观察组,90例单纯T2DM患者为对照组,选取同时期的60例健康体检者为健康组,研究对象均为男性。采用酶联免疫吸附法(ELISA试剂盒)检测3组血清25(OH)D、OC水平,比较3组血清25(OH)D、OC水平差异。收集观察组与对照组患者相关临床资料进行单因素分析,采用多因素Logistic回归分析T2DM合并LOH的相关影响因素,并绘制受试者工作特征曲线(ROC)分析血清25(OH)D、OC水平对T2DM合并LOH的诊断价值。结果3组血清25(OH)D、OC水平总体比较,差异有统计学意义(P<0.05)。与健康组比较,观察组和对照组25(OH)D、OC水平降低,差异有统计学意义(P<0.05);与对照组比较,观察组糖尿病病程延长,血清25(OH)D、OC、促卵泡生成素(Follicle-stimulating hormone,FSH)、黄体生成素(Luteinizing hormone,LH)、睾酮(Testosterone,T)水平降低,差异有统计学意义(P<0.05)。Logistic回归分析显示,血清25(OH)D、OC、FSH、LH、T水平均是影响T2DM合并LOH患者的相关因素(P<0.05)。血清25(OH)D、OC诊断T2DM合并LOH的最佳截断点分别为38.62 nmol/L、3.95 ng/mL,ROC曲线下面积(AUC)分别为0.865、0.886,敏感度分别为84.17%、85.00%,特异度分别为72.22%、70.00%,二者联合检验的AUC为0.912,敏感度与特异度分别为81.67%、78.89%。结论T2DM合并LOH患者血清25(OH)D、OC水平呈现异常表达,二者均是影响T2DM合并LOH的相关因素,对T2DM合并LOH具有良好诊断价值。

多元化中医理论指导下虫类药在泌尿男科疾病中的应用

虫类药治疗泌尿男科疾病古已有之,目前临床多依据医者经验辨证使用虫类药。本文从多元化中医理论视域出发,总结前人运用虫类药经验,认为在中医理论指导下的虫类药治疗泌尿男科疾病呈多角度、多元化发展,如从“热毒”、“瘀毒”、“芳香透窍”角度指导虫类药治疗慢性前列腺炎,从“肾虚”、“气血失调”、“络病”角度指导虫类药治疗勃起功能障碍等,此种发展趋势符合当前学者辨治泌尿男科疾病的主流思想。同时指出虫类药临床使用应关注的问题,以期为临床运用虫类药治疗泌尿男科疾病提供借鉴思路。

Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Late-onset hypogonadism （LOH） is closely related to secondary androgen deficiency in aged males, but the mechanism remains unclear. In this study, we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity. Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production. In Leydig cells from young and aged rats, treatment with wortmannin, an autophagy inhibitor, inhibited luteinising hormone （LH）-stimulated steroidogenic acute regulatory （STAR） protein expression and decreased testosterone production. In contrast, treatment with rapamycin, an autophagy activator, enhanced LH-stimulated steroidogenesis in Leydig cells from aged, but not young, rats. Intracellular reactive oxygen species （ROS） levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin. Furthermore, an increased level of ROS, induced by H2O2, resulted in LH-stimulated steroidogenic inhibition. Finally, knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells, which were associated with increased intracellular ROS level. These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells, which might be influenced by intracellular ROS levels.

Wnt5a基因沉默对骨髓间充质干细胞向睾丸间质细胞分化的影响

目的 通过siRNA干扰技术研究Wnt5a基因沉默对大鼠骨髓间充质干细胞(BMSCs)向睾丸间质细胞(LC)分化的初步机制。方法 采用流式细胞仪检测由中国科学院干细胞库提供的Sprague Dawley(SD)大鼠骨髓间充质干细胞株表面蛋白(CD29、CD44、CD45、CD90)的表达。BMSCs分为NC组、siRNA1组和siRNA2组,分别转染空载siRNA,Wnt5a-siRNA-1,Wnt5a-siRNA-2;采用RT-qPCR法检测Wnt5a-siRNA转染后Wnt5a及Wnt/β-catenin信号轴中LRP-5、β-catenin、TCF mRNA的表达;采用ELISA法检测Wnt5a-siRNA转染后Wnt5a及Wnt/β-catenin信号轴中LRP-5、β-catenin、TCF的蛋白表达;免疫荧光实验通过检测转染3 d的细胞表面标志物3β-羟化类固醇脱氢酶(3β-HSD),分析BMSCs向LC分化水平;倒置显微镜观察转染5 d细胞的形态学变化。ELISA法检测转染后LC的睾酮生成水平。结果 购买的大鼠BMSCs细胞株表面抗体CD29、CD44及CD90阳性表达及CD45阴性表达符合大鼠BMSCs的特异性抗体特征。与NC组比较,siRNA1组和siRNA2组Wnt/β-catenin信号轴中LRP-5、β-catenin、TCF的mRNA及蛋白表达量下降(P<0.05),睾酮分泌量均显著升高(P<0.05)。siRNA1组和siRNA2组LC特异性标记物3β-HSD染色阳性面积百分比明显高于NC组(P<0.01);细胞转染后形态学变化符合LC的形态特点。结论 Wnt5a-siRNA转染BMSCs细胞可显著抑制Wnt5a的mRNA和蛋白表达;Wnt5a基因沉默通过抑制Wnt/β-catenin信号通路发挥促进BMSCs向LC分化的作用。

男性迟发性性腺功能减退症中西医结合思路与方法探讨

随着人口老龄化进程的加剧,男性迟发性性腺功能减退症(late-onset hypogonadism,LOH)已成为中老年男性的多发病,采取中西医结合方法对本病的治疗与预防具有一定的优势。从辨证与辨病结合、中药与西药结合、宏观与微观结合、“病证结合”动物模型研究、流行病学调查与治未病思想结合5大方面进行探讨。认为在LOH防治与研究中,运用中西医结合思路与方法可提升诊断效率,减少药物不良反应,增强疗效,缩短治疗周期。解释LOH发病的部分中医机制,预测不同人群LOH发病率,早期干预,降低或避免LOH的发生。中西医结合思路与方法在LOH基础与临床研究中的运用,具有一定优势,值得推广运用。

雄蚕益肾方对雄性迟发性性腺功能减退大鼠睾丸组织生物钟基因表达的影响

目的:探讨雄蚕益肾方对雄性迟发性性腺功能减退症(LOH)大鼠睾丸组织细胞生物钟基因表达的影响。方法:48只8周龄雄性SD大鼠随机分为正常组,模型组,丙酸睾酮组,雄蚕益肾方低、中、高剂量组。模型组,丙酸睾酮组,雄蚕益肾方低、中、高剂量组大鼠腹腔注射480 mg/(kg·d)D-半乳糖(D-gal),连续注射56 d进行LOH造模,正常组大鼠每日腹腔注射相同体积生理盐水。造模成功后,雄蚕益肾方低、中、高剂量组分别给予10.4、20.8、41.6 g/(kg·d)体重剂量的雄蚕益肾方中药汤剂灌胃,每组每日均早、晚各灌胃1次;丙酸睾酮组大鼠肌注5.21 mg/(kg·d)体重剂量的丙酸睾酮,每周3次;正常组和模型组给予相同体积的蒸馏水灌胃;各组均连续操作28d。实验结束后,采血离心取上清液ELISA法检测睾酮(T)水平,取睾丸组织进行RT-qPCR、Western印迹分别检测BMAL1、NR1D1、PER2、CRY1、StAR、CYP11A1 mRNA表达量和蛋白表达水平。结果:模型组大鼠血清睾酮水平、睾丸组织BMAL1、NR1D1、PER2、CRY1、StAR、CYP11A1在mRNA表达量和蛋白表达水平均显著低于正常组(P<0.05);与模型组相比,丙酸睾酮组、雄蚕益肾方低、中、高剂量组大鼠血清睾酮显著升高(P<0.05),雄蚕益肾方高剂量组大鼠睾丸组织StAR mRNA表达量、CYP11A1 mRNA表达量和蛋白表达水平显著升高(P<0.05),雄蚕益肾方低、中、高剂量组大鼠睾丸组织StAR蛋白表达水平显著升高(P<0.05),丙酸睾酮组、雄蚕益肾方低、中、高剂量组大鼠睾丸组织BMAL1、NR1D1蛋白表达水平及PER2蛋白表达水平和mRNA表达量显著升高(P<0.05),雄蚕益肾方中、高剂量组大鼠睾丸组织BMAL1 mRNA表达量、CRY1蛋白表达水平显著升高(P<0.05),雄蚕益肾方低、中、高剂量组大鼠睾丸组织NR1D1 mRNA表达量显著升高(P<0.05),丙酸睾酮组、雄蚕益肾方中、高剂量组大鼠睾丸组织CRY1 mRNA表达量显著升高(P<0.05)。结论:雄蚕益肾方能上调LOH大鼠睾丸组织生物钟基因BMAL1、NR1D1、PER2、CRY1以及睾酮合成相关基因StAR、CYP11A1 mRNA表达量和蛋白表达水平,同时提高血清睾酮水平,可能是雄蚕益肾方干预LOH的机制之一。