磺基转移酶预测米诺地尔治疗雄激素性秃发疗效的研究
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摘要
目的:评价磺基转移酶的活性及其mRNA表达量指标用于预测米诺地尔治疗雄激素性秃发(AGA)疗效的可行性。方法:(1)研究选取135例米诺地尔治疗组和10例手术治疗组AGA患者。米诺地尔治疗组患者拔取生长期头发,测量磺基转移酶的活性(用吸光度A值表示)并予以2%米诺地尔于脱发区连续治疗6个月,在初诊和治疗6个月时进行全头毛发照相评估,根据患者治疗前后脱发面积和程度的变化判断疗效,根据疗效进一步分组为改善组98例,控制组23例,无效组14例;(2)手术组AGA患者拔取生长期头发,并用环钻打孔法取其毛囊;米诺地尔组AGA患者只拔取生长期头发,均用实时荧光定量聚合酶链反应(q PCR)检测磺基转移酶的mRNA表达量(用B值表示)。结果:(1)米诺地尔治疗组患者中的改善组、控制组与无效组两两比较,磺基转移酶活性的差异均有统计学意义(P=0.000,P=0.000,P=0.036),(2)预测2%米诺地尔疗效的磺基转移酶活性的最佳阈值是0.430,灵敏度为83%,特异度为95%;(3)毛囊和头发中的磺基转移酶mRNA表达量呈正相关(r=0.703,n=10,P=0.023)。磺基转移酶mRNA表达量和就诊时脱发严重程度呈正相关(r=0.320,n=47,P=0.028)。磺基转移酶mRNA表达量和疗效积分、磺基转移酶的活性均无相关性(r=0.038,n=29,P=0.846;r=-1.515,n=47,P=0.311)。结论:(1)磺基转移酶的活性可以预测2%的米诺地尔治疗AGA的疗效;(2)无创的拔发法可取代传统有创的环钻打孔取毛囊法来检测磺基转移酶mRNA的表达量;(3)磺基转移酶mRNA可能存在转录后水平、翻译水平和翻译后水平的修饰,从而影响了磺基转移酶的活性。
Objective:To determine whether the sulfotransferase activity and its mRNA expression levels can serve as biomarkers for predicting the therapeutic efficacy of minoxidil for androgenic alopecia(AGA).Methods:(1)135 AGA patients treated with minoxidil(minoxidil group)and 10 surgically treated AGA(operation group)were enrolled in this study.In the minoxidil group,hairs at anagen phase were pulled out,and sulfotransferase activity was measured(a value of absorbance).2% of minoxidil was applied the alopecia area for 6 months.Global photography assessment was conducted at initial visit and sixth months of treatment.According to the changes in the affected area and extent of hair loss following the treatment,therapeutic efficacy was graded as improved(98),under control(23) and ineffective groups(14);(2)In operation group,hairs at anagen phase were also pulled out,but hair follicles were obtained using the drill punch method.Hair follicles at anagen phase were also obtained from 47 patients in minoxidil group.Expression levels of sulfotransferase mRNA were assessed by real-time fluorescence quantitative polymerase chain reaction(q PCR).Results:(1)In minoxidil group,sulfotransferase activity differed significantly among improved,under control and the ineffective groups(P=0.000,P=0.000,P=0.036);(2)The best threshold of sulfotransferase activity in predicting efficacy of 2% minoxidil was0.430,with sensitivity of 83%,and the specificity of 95%;(3)Expression levels of sulfotransferase mRNA in hair follicles and hairs correlated positively(r=0.703,n=10,P=0.023).Expression levels of sulfotransferase mRNA correlated positively with the severity of hair loss prior to the treatment(r=0.320,n=47,P=0.028).But there was no association among expression levels of sulfotransferase mRNA,cumulative scores of efficacy and sulfotransferase activity(r=0.038,n=29,P=0.846;r=-1.515,n=47,P=0.311).Conclusions:(1)Sulfotransferase activity can be used to assess the efficacy of 2% minoxidil for AGA;(2)The noninvasive method of pulling hair can substitute for the traditional invasive drill punch method to measure expression levels of sulfotransferase mRNA;(3)Sulfotransferase mRNA may regulate sulfotransferase activity at post-transcriptional,translational and post-translational levels.
Objective:To determine whether the sulfotransferase activity and its mRNA expression levels can serve as biomarkers for predicting the therapeutic efficacy of minoxidil for androgenic alopecia(AGA).Methods:(1)135 AGA patients treated with minoxidil(minoxidil group)and 10 surgically treated AGA(operation group)were enrolled in this study.In the minoxidil group,hairs at anagen phase were pulled out,and sulfotransferase activity was measured(a value of absorbance).2% of minoxidil was applied the alopecia area for 6 months.Global photography assessment was conducted at initial visit and sixth months of treatment.According to the changes in the affected area and extent of hair loss following the treatment,therapeutic efficacy was graded as improved(98),under control(23) and ineffective groups(14);(2)In operation group,hairs at anagen phase were also pulled out,but hair follicles were obtained using the drill punch method.Hair follicles at anagen phase were also obtained from 47 patients in minoxidil group.Expression levels of sulfotransferase mRNA were assessed by real-time fluorescence quantitative polymerase chain reaction(q PCR).Results:(1)In minoxidil group,sulfotransferase activity differed significantly among improved,under control and the ineffective groups(P=0.000,P=0.000,P=0.036);(2)The best threshold of sulfotransferase activity in predicting efficacy of 2% minoxidil was0.430,with sensitivity of 83%,and the specificity of 95%;(3)Expression levels of sulfotransferase mRNA in hair follicles and hairs correlated positively(r=0.703,n=10,P=0.023).Expression levels of sulfotransferase mRNA correlated positively with the severity of hair loss prior to the treatment(r=0.320,n=47,P=0.028).But there was no association among expression levels of sulfotransferase mRNA,cumulative scores of efficacy and sulfotransferase activity(r=0.038,n=29,P=0.846;r=-1.515,n=47,P=0.311).Conclusions:(1)Sulfotransferase activity can be used to assess the efficacy of 2% minoxidil for AGA;(2)The noninvasive method of pulling hair can substitute for the traditional invasive drill punch method to measure expression levels of sulfotransferase mRNA;(3)Sulfotransferase mRNA may regulate sulfotransferase activity at post-transcriptional,translational and post-translational levels.
引文
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[2]雎恒春,孙蔚凌,范卫新.毛囊中磺基转移酶活性与局部外用米诺地尔治疗雄激素性秃发疗效相关性研究[J].临床皮肤科杂志,2017,(6):395-400.
[3]Lee WS,Ro BI,Hong SP,et al.A new classification of pattern hair loss that is universal for men and women:basic and specific(BASP)classification[J].J Am Acad Dermatol,2007,57(1):37-46.
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[5]宋闯,周映,胡莉芳,等.雄激素性秃发患者家族遗传史的临床分析研究[J].临床皮肤科杂志,2015,(12):770-773.
[6]Gupta AK,Charrette A.Topical minoxidil:systematic review and meta-analysis of its efficacy in androgenetic alopecia[J].Skinmed,2015,13(3):185-189.
[7]Han JH,Kwon OS,Chung JH,et al.Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle[J].J Dermatol Sci,2004,34(2):91-98.
[8]Messenger AG,Rundegren J.Minoxidil:mechanisms of action on hair growth[J].Br J Dermatol,2004,150(2):186-194.
[9]Yano K,Brown LF,Detmar M.Control of hair growth and follicle size by VEGF-mediated angiogenesis[J].J Clin Invest,2001,107(4):409-417.
[10]Hsu CL,Liu JS,Lin AC,et al.Minoxidil may suppress androgen receptor-related functions[J].Oncotarget,2014,5(8):2187-2197.
[11]Buhl AE,Waldon DJ,Baker CA,et al.Minoxidil sulfate is the active metabolite that stimulates hair follicles[J].J Invest Dermatol,1990,95(5):553-557.
[12]Baker CA,Uno H,Johnson GA.Minoxidil sulfation in the hair follicle[J].Skin Pharmacol,1994,7(6):335-339.
[13]Goren A,Castano JA,Mccoy J,et al.Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia[J].Dermatol Ther,2014,27(3):171-173.
[2]雎恒春,孙蔚凌,范卫新.毛囊中磺基转移酶活性与局部外用米诺地尔治疗雄激素性秃发疗效相关性研究[J].临床皮肤科杂志,2017,(6):395-400.
[3]Lee WS,Ro BI,Hong SP,et al.A new classification of pattern hair loss that is universal for men and women:basic and specific(BASP)classification[J].J Am Acad Dermatol,2007,57(1):37-46.
[4]中华医学会皮肤性病学分会毛发学组.中国雄激素性秃发诊疗指南[J].临床皮肤科杂志,2014,43(3):182-186.
[5]宋闯,周映,胡莉芳,等.雄激素性秃发患者家族遗传史的临床分析研究[J].临床皮肤科杂志,2015,(12):770-773.
[6]Gupta AK,Charrette A.Topical minoxidil:systematic review and meta-analysis of its efficacy in androgenetic alopecia[J].Skinmed,2015,13(3):185-189.
[7]Han JH,Kwon OS,Chung JH,et al.Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle[J].J Dermatol Sci,2004,34(2):91-98.
[8]Messenger AG,Rundegren J.Minoxidil:mechanisms of action on hair growth[J].Br J Dermatol,2004,150(2):186-194.
[9]Yano K,Brown LF,Detmar M.Control of hair growth and follicle size by VEGF-mediated angiogenesis[J].J Clin Invest,2001,107(4):409-417.
[10]Hsu CL,Liu JS,Lin AC,et al.Minoxidil may suppress androgen receptor-related functions[J].Oncotarget,2014,5(8):2187-2197.
[11]Buhl AE,Waldon DJ,Baker CA,et al.Minoxidil sulfate is the active metabolite that stimulates hair follicles[J].J Invest Dermatol,1990,95(5):553-557.
[12]Baker CA,Uno H,Johnson GA.Minoxidil sulfation in the hair follicle[J].Skin Pharmacol,1994,7(6):335-339.
[13]Goren A,Castano JA,Mccoy J,et al.Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia[J].Dermatol Ther,2014,27(3):171-173.