小剂量环磷酰胺治疗尖锐湿疣对角质形成细胞的干细胞性及分化影响  

Effect of Low-dose Cyclophosphamide on Stem Cell Proliferation and Differentiation of Keratinocytes in Condyloma Acuminata

作　　者：吴佳怿 谌素素 曹育春[2] 张勇[2] WU Jiayi;SHEN Susu;CAO Yuchun;ZHANG Yong(Department of Pathology,Beijing Cancer Hospital,Beijing 100142,China;Department of Dermatology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Wuhan YZY Biopharma Co.Ltd,Wuhan 430075,China)

机构地区：[1]北京大学肿瘤医院病理科,北京100142 [2]华中科技大学同济医学院附属同济医院皮肤科,武汉430030 [3]武汉友芝友生物制药有限公司,武汉430075

出　　处：《医药导报》2020年第10期1375-1378,共4页Herald of Medicine

基　　金：国家自然科学基金资助项目(81472000)。

摘　　要：目的研究小剂量环磷酰胺(CTX)治疗尖锐湿疣(CA)对表皮角质形成细胞(KCs)的干细胞性及分化的影响。方法20例初发CA患者作为对照组(CA组);8例小剂量CTX治疗CA患者为治疗组(CTX组),10例正常包皮环切患者为空白对照组(NS组)。采用免疫组化方法,对比研究表皮干细胞标志物P63和整合素α6(ITGA6)以及成熟KCs标志物K10在3组之间的表达差异。结果P63及ITGA6表达:NS组中主要表达于基底层;CA组表达量较NS组增多(P<0.01),而且表达部位不仅局限于基底层,在靠近基底层的棘层中也存在较多阳性表达;CTX组表达较CA组明显减少(P<0.01),阳性表达位置主要在基底层,而靠近基底层的棘层中仅有少量表达。K10表达:NS组表达于基底层以上的表皮结构中,基底层表达为阴性;CA组表达量较NS组明显减少(P<0.01),基底层不表达;CTX组中表达量较CA组明显增加(P<0.01)。结论小剂量CTX疗法治疗后能使CA疣体中KCs的干细胞性减弱,而细胞终末分化能力增强。Objective To study the mechanisms of low-dose cyclophosphamide(CTX)treatment for condyloma acuminata(CA)on the proliferation and differentiation of keratinocytes in the epidermis of CA.Methods A total of 20 patients with primary CA were selected as CA group,and 8 cases treated with low-dose CTX were selected as the experimental group(CTX group),and 10 normal circumcision patients were selected as the blank control group(NS group).The expression and distribution of epidermal stem cell’s markers including P63,integrinα6(ITGA6)and marker for keratinocytes K10 were tested and compared among the three groups by using immunohistochemistry.Results The immunohistochemical results showed that levels of P63 and ITGA6 in CA group were significantly higher than those in NS group and CTX group.However,the expression of P63 and ITGA6 in the NS group was similar to that in the CTX group.Moreover,the localization of P63 and ITGA6 in CA group was no more than in the basal layer of epidermis,and even more in the spinous layer near the basal layer compared with the other two groups.In addition,K10 and mature keratinocytes’marker was lower in CA group,but significantly increased after the low-dose CTX treatment,which was similar to that in NS group.The localization of K10 also was changed among three groups.K10 was localized upon the basal layer and almost negative in the basal layer,which was significantly decreased in the CA group.Interestingly,after a whole course of low-dose CTX treatment,K10 markedly increased compared to the CA group,and distributed upon the basal layer.Conclusion The epidermal stem cells within the CA warts after taking low-dose cyclophosphamide had less ability to proliferate but were more likely to differentiate,which means that low-dose cyclophosphamide treatment may suppress the proliferation of local epidermal stem cells and promote differentiation.

关 键 词：尖锐湿疣 人乳头瘤病毒 小剂量环磷酰胺疗法 干细胞性 表皮终末分化细胞 

分 类 号：R979.1[医药卫生—药品] R759.5[医药卫生—药学]