雄激素性秃发患者治疗前后头发中微量元素的变化检测

<正>非那雄胺(商品名:保法止)1998年被美国食品药品管理局(FDA)批准用于治疗雄激素性秃发(androgenic alopecia,AGA),它是Ⅱ型5α还原酶的特异性抑制剂,能不可逆地结合Ⅱ型5α还原酶,从而抑制睾酮转化为二氢睾酮(dihydrotestosterone,DHT),使血清及组织中DHT的浓度显著下降。国外有研究表明,每天1 mg非那雄胺能显著降低DHT水平,且DHT的下降与临床疗效相关,对于DHT偏高的26岁以下患者,在治疗12个月时血清DHT水平可下降50%~([1])。此外,有研究对290例口服非那雄胺的患者随访5年,发现     

雄激素性秃发与相关信号传导通路的研究进展北大核心CSCD

雄激素性秃发(androgeneticalopecia,AGA是一种常见的慢性进行性疾病,当下全世界超过数百万人因AGA受不同程度的身心影响。但尽管发病率很高,AGA临床上的有效治疗手段却相对有限。AGA最主要的病机是高活性睾酮经5-α还原酶作用生成过多双氢睾酮(DHT),二者与雄激素受体结合后引起毛囊萎缩、毛发生长抑制。现有的AGA治疗药物多是以雄激素、5α-还原酶、DHT、雄激素受体等为靶点阻断这一雄激素途径,但药物种类有限及长期使用带来的不良反应都大大降低了患者治疗的依从性。因此,与AGA相关的信号传导通路及其主导因子包括Wnt/β-catenin通路、骨形成蛋白(BMP)通路、成纤维细胞因子(FGF)通路、转化生长因子β(TGF-β)通路、胰岛素样生长因子(IGF)通路等,都有望成为AGA治疗安全增效的新靶点,推动AGA的临床研究及应用进展。     

三七总皂苷对雄激素性脱发小鼠的改善作用及机制研究

目的：明确三七总皂苷（PNS）对雄激素性脱发（AGA）小鼠的治疗效果及其作用机理。方法：40只C57BL/6雄性小鼠随机分为空白组、模型组、阳性组、三七总皂苷组,每组10只。除空白组外其余各组小鼠皮下注射丙酸睾酮溶液建立雄激素性脱发模型后,每组给予相应试剂或蒸馏水处理。对每组脱发区的毛囊数目、终毛毛囊、毳毛毛囊进行计数并计算终毛/毳毛的比值。测定小鼠血清睾酮、血管内皮生长因子（VEGF）的含量以及小鼠皮肤组织VEGF、转化生长因子-β1 （TGF-β1）表达量。结果：与空白组比较,模型组小鼠背部毛发明显稀疏,总毛囊数目、终毛毛囊数目、终毛/毳毛比值、血清和皮肤组织中VEGF表达量明显下降,皮肤组织中TGF-β1表达量显著上升（均P<0.01）;与模型组比较,三七总皂苷组小鼠毛发增多可见大量新生绒毛;小鼠皮肤总毛囊数目、终毛毛囊数目明显增加,终毛/毳毛比值升高;小鼠血清和皮肤组织VEGF表达量明显升高;TGF-β1表达量降低,差异均有统计学意义(均P<0.05)。结论：三七总皂苷对C57BL/6AGA小鼠模型有改善作用,其作用机制可能与上调血清和皮肤组织中VEGF表达以及下调皮肤组织中TGF-β1表达有关。     

雄激素性脱发患者血清雄激素水平测定

采用化学发光法和酶联免疫吸附试验（ELISA）对80例雄激素性脱发（AGA）患者血清睾酮（T）、游离睾酮（FT）和二氢睾酮（DHT）的含量进行检测。结果：男、女患者的FT、DHT水平均高于正常对照组（P〈0．05）。进一步证实了AGA的发病机制与雄激素水平密切相关，提示血清FT和DHT的测定对AGA的临床诊治具有一定的参考意义。     

Expression of BMP type ⅠA receptor in the scalp of AGA patients and its significance

目的:探讨骨形成蛋白Ⅰ型受体(BMPR-Ⅰ)A在正常人及雄激素源性脱发(androgenetic alopecia,AGA)患者头皮毛囊中的表达及其意义.方法:采用Western blot、免疫组化及RT-PCR分析8例AGA患者额顶部脱发区与枕部非脱发区毛囊及11例正常人头皮毛囊中BMPR-ⅠA蛋白及基因水平表达差异;毛囊分组培养,观察双氢睾酮(dihydrotestosterone,DHT)10-9mol/L对BMPR-ⅠA表达及毛囊生长的影响.结果:各组头皮毛囊均可见BMPR-ⅠA阳性染色.与正常毛囊相比,AGA患者脱发区毛囊阳性染色A值降低(P ＜ 0.05).Western blot结果显示,AGA患者头顶部毛囊BMPR-ⅠA含量较正常人下调,目的蛋白与内参灰度比由1.733±0.058下调为0.396±0.036(P ＜ 0.05);AGA枕部毛囊目的蛋白与内参灰度比值为1.574±0.039,与正常人组差异无统计学意义.毛囊培养DHT组与生理盐水对照组相比,目的蛋白与内参灰度比由3.441±0.172下降为0.367±0.026(P ＜ 0.05).RT-PCR结果示,AGA脱发区毛囊BMPR-ⅠA mRNA下调为正常组的53%(P ＜ 0.05),AGA枕部无明显下调;毛囊培养DHT组下调为对照组的13%(P ＜ 0.05).结论:AGA脱发区毛囊与DHT组毛囊BMPR-ⅠA表达均降低,提示BMPR-ⅠA表达下降部分是由DHT升高引起;DHT可引起的毛囊生长减慢及退行性变;BMPR-ⅠA表达下降可能是DHT升高的直接作用或者是AGA生长期与退行期毛囊比例下降的代偿机制;其参与AGA发病可能与毛干及内根鞘形成障碍引起毛发脱落有关.     

Clascoterone对SZ95人皮脂腺细胞增殖、脂质合成和炎症因子表达的影响

目的：明确clascoterone对雄激素作用下人皮脂腺细胞增殖、脂质合成和炎症因子表达的影响,探索其抗痤疮机制。方法：体外培养SZ95人皮脂腺细胞,分为双氢睾酮（DHT）组、clascoterone组,clascoterone+DHT组,CCK8法检测细胞增殖,尼罗红染色检测细胞内中性脂质,蛋白免疫印迹检测脂质合成相关基因表达。酶联免疫吸附检测细胞培养上清液中炎症因子蛋白,RT-qPCR检测细胞因子转录水平。结果：与DHT组相比,clascoterone和DHT共培养24h后细胞数量出现显著下降（P＜0.01）;在亚油酸（LA）作用下,clascoterone+DHT组细胞内中性脂质低于DHT组（P＜0.0001）;此外,clascoterone+DHT组PPARγ、PLIN2、FASN、SCD1等脂质合成相关基因的表达、炎症因子IL-1α、IL-1β、IL-6、IL-8及相应蛋白水平低于DHT组(均P<0.05)。结论：clascoterone体外对人皮脂腺细胞增殖、脂质合成相关基因和炎症因子具有调节作用,可能是其抗痤疮治疗机制之一。     

保法止~(非那雄胺片)

保法止R（Propecia）为每片含有１mg非那雄胺（finasteride的片剂，１９９７年１２月美国FDA批准用于男性型雄激素性脱发。１非那雄胺的药理及药代动力学非那雄胺，其化学名称为N－（１，１－二甲基乙基）－３－氧－４－氮杂－５α－甾－１－烯－１７β－酰胺。是一种合成的甾体类化合物。它是雄激素睾酮代谢成为双氢睾酮过程中的细胞内酶Ⅱ型５α还原酶的特异性抑制剂。非那雄胺对雄激素受体没有亲和力，也没有雄激素样、抗雄激素样、雌激素样、抗雌激素样或促孕作用。对该酶的抑制能阻碍外周组织中睾酮向双氢睾酮的转化，使血清及组织…     

101B对人毛乳头细胞增殖及4种脱发相关基因表达的影响

目的:通过检测101B对体外培养人毛乳头细胞增殖及脱发相关基因表达的影响,分析其可能的抗雄激素性秃发(AGA)效果。方法:体外培养人毛乳头细胞经101B[对照二氢睾酮(DHT)]处理后,采用Cell Counting Kit-8(CCK-8)法检测细胞增殖变化,并筛选4个基因通过实时荧光定量PCR(RT-PCR)方法检测其表达量。结果:101B能促进毛乳头细胞的增殖,0.4%作用浓度下细胞增殖率提高30%;101B抑制5α-还原酶2(SRD5A2)、雄激素受体(AR)、凋亡因子p53与转化生长因子(TGF)-β2的表达,0.5%作用浓度下p53与AR的RNA表达量较空白对照降低40%以上,而101B与DHT共同处理毛乳头细胞能显著抑制DHT对SRD5A2表达的激活作用。结论:101B在体外培养人毛乳头细胞中能通过抑制SRD5A2、AR、p53与TGF-β2基因的作用来发挥抗雄激素的作用。     

Anti-DNP IgE 联合 DNFB 诱导免疫性接触性荨麻疹小鼠模型的建立

目的：利用抗－二硝基苯酚（anti-DNP）IgE单克隆抗体和2,4－二硝基氟苯（DNFB）建立免疫性接触性荨麻疹小鼠模型。方法：将36只BALB／c小鼠随机分成3组,每组12只：造模组小鼠尾静脉注射anti-DNP IgE单克隆抗体,24 h后在小鼠双耳涂DNFB进行激发;单纯IgE组仅注射anti-DNP IgE单克隆抗体,空白对照组小鼠注射生理盐水,均在24 h后在小鼠双耳涂生理盐水。观察小鼠在14 d内的风团、瘙痒、耳朵肿胀度情况,并检测血清中IgE、IL-4、IFN-γ、组胺水平和皮肤病理。结果：造模组全部小鼠产生风团;与其它两组相比,造模组小鼠搔抓次数、耳朵肿胀度及组胺血清水平均明显升高（P值均＜0．01）,但三组间IgE、IL-4、IFN-γ水平无明显差异（P＞0.05）。结论：静脉注射anti-DNP IgE单克隆抗体联合外用DNFB可快速、可靠地建立免疫性接触性小鼠荨麻疹模型。     

中药内服联合非那雄胺治疗男性雄激素性秃发临床观察及依从性分析

目的观察中药内服联合1 mg非那雄胺治疗男性雄激素性秃发(AGA)的疗效。方法青年男性AGA患者共70例,随机分为2组,分别予口服1 mg非那雄胺联合中药、单纯口服中药治疗,观察2组治疗3、6个月时头皮局部症状(油腻、瘙痒、头屑)、毛发生长改善情况。结果中药内服联合1 mg非那雄胺治疗湿热青年男性型脱发28例(剔除脱落7例),止脱率为89.3%,有效率为82.2%;对照组收录27例(剔除脱落8例),止脱率为85.2%,有效率为55.6%,治疗组止脱率较对照组差异无统计学意义(P0.05),治疗组的有效率要高于对照组,差异有统计学意义(P0.05);经6个月治疗后,治疗组与对照组组内头皮油腻、瘙痒、头屑情况较治疗前均有明显好转,差异有统计学意义(P0.05),2组间头发油腻、头屑、头皮瘙痒情况治疗后差异无统计学意义(P0.05);治疗组脱落率为20.0%,对照组脱落率为22.86%,低于单纯口服非那雄胺脱落率;秃发的疗效同秃发的严重程度呈负相关性。结论单纯中药内服可显著改善头皮局部症状(油腻、头屑及瘙痒),毛发生长改善较慢;中药内服联合1 mg非那雄胺治疗AGA可较快的控制秃发情况,缓解头皮症状,提高患者依从性,降低脱落率,提高疗效。     

Androgen responsive genes as they affect hair growth

Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.     

低剂量非那雄胺控制男性型秃发临床观察

目的通过随机双盲对照试验评估每日口服非那雄胺1mg治疗2年有效并满意后,减量为5mg/周及1mg隔1日口服治疗中国男性型秃发的疗效。方法选择非那雄胺治疗2年或2年以上的男性型秃发患者175例,随机分为非那雄胺减量治疗组88例和安慰剂对照组87例,分别口服非那雄胺(1~24周5mg/周,24~48周1mg隔日1次口服)或安慰剂48周。并由皮肤科医师在24~48周时对治疗前、后的头发进行显微照像并评价,同期患者也进行自我评价。结果治疗前、后头发显微照像分析认为,治疗24周时非那雄胺减量治疗组脱发率为48.86%,而安慰剂对照组为98.85%,差异有统计学意义(P<0.05)。治疗48周后非那雄胺减量治疗组的脱发率为73.86%,安慰剂对照组为100%,差异有统计学意义。患者在24周和48周时的自我评价的结果也与之相似。结论低剂量口服非那雄胺维持治疗对中国男性型秃发患者脱发有一定作用。     

参麦注射液对百草枯所致肺损伤的保护作用

目的探讨参麦注射液在百草枯中毒所致肺损伤中的作用。方法120只SD大鼠随机分为百草枯中毒组（APP）,参麦注射液治疗组（SM1,SM2,SM3）。HE染色观察参麦注射液治疗组组织结构变化,采用免疫组织化学法测定各组肺组织中TGF—β1、IL-1β的表达水平。结果百草枯中毒组肺组织充血水肿明显,肺泡破坏严重,治疗组有所减轻;各治疗组与百草枯中毒组之间转化生长因子β-1（TGF—β1）,白细胞介素-1β（IL—1β）水平均较治疗组明显降低,各治疗组随剂量的增加,TGF-β1,IL-1β水平有明显下降,差异有显著性（P〈0．05）。结论参麦注射液在百草枯所致中毒大鼠肺损伤中能使TGF—β1,IL-1β表达水平下调,减轻肺泡炎症和充血程度,减轻百草枯中毒所致肺损伤,延缓和抑制肺纤维化的发生、发展。     

The novel drug CS-891 inhibits 5alpha-reductase activity in freshly isolated dermal papilla of human hair follicles

The local conversion of testosterone (T) to the more potent androgen dihydrotestosterone (DHT) by 5alpha-reductase (5aR) is implicated in the pathogenesis of androgenetic alopecia (AGA). Recently, the clinical effectiveness of finasteride, a selective type II 5aR inhibitor, in treating AGA has been documented, and these clinical studies have shown that circulating DHT is lowered by 60-70% in men taking finasteride. The source of the residual circulating DHT is presumed to be due to type I 5aR activity which is not affected by finasteride. Several novel compounds with potent dual inhibitory activity on both isoenzymes have been described and CS-891 is one of them. This compound may be likewise effective in the prevention or treatment of AGA. As a prerequisite for such an action CS-891 should be able to inhibit 5aR activity in its target tissue: the hair follicles (HF). Here we report on the capability of CS-891 to inhibit 5aR activity in dermal papillae (DP) of human HF.     

Long-term treatment with finasteride 1 mg decreases the likelihood of developing further visible hair loss in men with androgenetic alopecia (male pattern hair loss)

There are no reports on the effects of pharmacologic treatment on the likelihood of developing further visible hair loss in men with androgenetic alopecia (AGA). Our objectives were to examine whether finasteride 1 mg treatment decreases the likelihood of developing further visible hair loss in men with AGA. We conducted an analysis of global photographic assessment data from two Phase III trials in which 1553 men with AGA received finasteride 1 mg/day or placebo for up to 5 years. Finasteride 1 mg treatment led to a 93% decrease relative to placebo in the 5-year likelihood of developing further visible hair loss (95% CI: 89-97%; p < 0.001). We conclude that, in men with AGA, treatment with finasteride 1 mg/day over 5 years led to a marked and sustained decrease in the likelihood of developing further visible hair loss.     

Evaluation of androgens in the scalp hair and plasma of patients with male-pattern baldness before and after finasteride administration

BACKGROUND: Finasteride, a competitive inhibitor of the enzyme 5alpha-reductase II, is widely used as a medical treatment for patients with male-pattern baldness (MPB), which is affected by the distribution of androgenic steroids. It is also notable that the androgenic effect in MPB is different for each region of the head. OBJECTIVES: To study the effect of the drug finasteride, we quantified androgenic steroids in the vertex and occipital scalp hair and in the plasma of patients with MPB. METHODS: The patients with MPB, aged 23-52 years, were treated with finasteride 1 mg daily for 5 months. The hair and plasma samples were hydrolysed, extracted with n-pentane, and derivatized with MSTFA:NH4I:DTE (1000:4:5, v/w/w). We analysed the concentrations of dihydrotestosterone (DHT) and testosterone (T) in the hair and plasma using gas chromatography-mass spectrometry (GC-MS). RESULTS: In the hair, the ratio of DHT/T was decreased in the vertex scalp hair after the individual received finasteride (P < 0.005). However, we found no significant difference in the ratio of DHT/T in the occipital scalp hair before and after individuals received finasteride. Like the results in the vertex scalp hair, the ratio of DHT/T in the plasma was remarkably decreased after finasteride administration (P < 0.001). CONCLUSIONS: This study supports the effect of finasteride in patients with MPB by examining the decreased level of DHT/T in scalp hair and in plasma. Thus, in view of the androgenic effect in the different hair regions, the vertex scalp hair plays a more important role for patients with MPB treated with finasteride than does the occipital hair.     

The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia.

BACKGROUND: Data suggest that androgenetic alopecia is a process dependent on dihydrotestosterone (DHT) and type 2 5alpha-reductase. Finasteride is a type 2 5alpha-reductase inhibitor that has been shown to slow further hair loss and improve hair growth in men with androgenetic alopecia. OBJECTIVE: We attempted to determine the effect of finasteride on scalp skin and serum androgens. METHODS: Men with androgenetic alopecia (N = 249) underwent scalp biopsies before and after receiving 0.01, 0.05, 0.2, 1, or 5 mg daily of finasteride or placebo for 42 days. RESULTS: Scalp skin DHT levels declined significantly by 13.0% with placebo and by 14.9%, 61.6%, 56. 5%, 64.1%, and 69.4% with 0.01, 0.05, 0.2, 1, and 5 mg doses of finasteride, respectively. Serum DHT levels declined significantly (P <.001) by 49.5%, 68.6%, 71.4%, and 72.2% in the 0.05, 0.2, 1, and 5 mg finasteride treatment groups, respectively. CONCLUSION: In this study, doses of finasteride as low as 0.2 mg per day maximally decreased both scalp skin and serum DHT levels. These data support the rationale used to conduct clinical trials in men with male pattern hair loss at doses of finasteride between 0.2 and 5 mg.     

Use of finasteride in the treatment of men with androgenetic alopecia (male pattern hair loss)

Finasteride, a type 2-selective 5alpha-reductase inhibitor, was approved in 1997 as the first oral pharmacologic therapy for the treatment of men with androgenetic alopecia (AGA; male pattern hair loss). Originally developed for the treatment of men with benign prostatic hyperplasia (BPH) at a dose of 5 mg/day, finasteride has a well-established, excellent safety profile. Subsequent studies demonstrated that finasteride was an effective treatment for men with AGA at an optimal dose of 1 mg/day. This report summarizes the published peer-reviewed literature on the use of finasteride in the treatment of men with AGA, including the data on long-term (5 years) use of finasteride in a placebo-controlled clinical trial environment.     

An open, randomized, comparative study of oral finasteride and 5% topical minoxidil in male androgenetic alopecia

BACKGROUND AND AIM: Androgenetic alopecia (AGA) is undoubtedly the most common form of hair loss in males. It is a condition which may cause cosmetic and psychosocial problems in androgen-dependent cases. In this open, randomized and comparative study we evaluated the efficacy of oral finasteride and 5% topical minoxidil treatment for 12 months in 65 male patients with mild to severe AGA. METHODS: We randomly assigned 40 (61.53%) patients to receive 1 mg/day oral finasteride for 12 months, and 25 (38.47%) patients applied 5% topical minoxidil solution twice daily for 12 months. RESULTS: There were no significant differences between the 2 groups considering age, age of onset of hair loss, family history and type of hair loss (p > 0.05). In the clinical evaluation at the endpoint of treatment, the clinical cure rates (i.e. increased intensity of hair) were 80% (32/40) for the oral finasteride group and 52% (13/25) for the 5% topical minoxidil group. Encountered side effects were all mild, and there was no need to stop the treatment. In the group given oral finasteride, side effects were noted in 7 patients: 6 patients suffered from loss of libido, and 1 patient had an increase in other body hairs; irritation of the scalp was seen in 1 patient in the group administered 5% minoxidil. These adverse events disappeared as soon as the treatment was stopped. The laboratory data on both drug groups did not show any statistically or clinically significant intragroup changes from baseline values to the endpoint (p > 0.05), except the level of serum total testosterone which was increased, and free testosterone and serum prostate-specific antigen in the finasteride group which were statistically decreased from baseline values to the endpoint (p < 0.05). CONCLUSION: In this comparative study of systemic finasteride and topical minoxidil, it was concluded that both drugs were effective and safe in the treatment of mild to severe AGA, although oral finasteride treatment was more effective (p < 0.05). Adverse events were not considered important either, and these side effects disappeared as soon as the treatment was stopped.