Gafter-Gvili Anat, Kalechman Yona, Sredni Benjamin, Gal Rivka, Gafter Uzi
Departments of Nephrology and Pathology, Golda-Hasharon Campus, Rabin Medical Center, Petah Tikva, Israel.
Arch Dermatol Res. 2004 Nov;296(6):265-9. doi: 10.1007/s00403-004-0516-x.
Cyclosporin A (CsA) often causes hair growth in transplant recipients. Our objectives were to evaluate the effect of CsA on follicular hair keratinocyte growth in nude mice by assessing their proliferation in vivo, and to assess the ability of CsA to prevent follicular keratinocyte apoptosis in vivo and chemotherapy-induced keratinocyte apoptosis in vitro.
Nude mice were fed various daily doses of CsA (10-100 mg/kg). Dorsal skin sections stained with hematoxylin and eosin, followed by immunostaining with 4-deoxybromouridine, were examined for determination of hair follicle number and hair follicle keratinocyte proliferation. Follicular keratinocytes were isolated and examined for apoptotic status. Apoptosis was induced in vitro in a keratinocyte cell line by 4-hydroperoxycyclophosphamide. The antiapoptotic effects of various CsA concentrations (0.1-5 microg/ml) were measured by annexin-V/propidium iodide binding.
CsA caused a dose-dependent increase in the number of hair follicles but had no effect on follicular keratinocyte proliferation. Treatment with CsA decreased the number of apoptotic follicular keratinocytes. In vitro, there was a dose-dependent inhibition of the extent of early and late apoptosis of treated keratinocytes.
CsA may induce hair growth by increasing the number of hair follicles and inhibiting apoptosis of follicular keratinocytes, thereby delaying hair follicle regression.
环孢素A(CsA)常导致移植受者毛发增多。我们的目的是通过评估裸鼠体内毛囊角质形成细胞的增殖情况,来评价CsA对其生长的影响,并评估CsA在体内预防毛囊角质形成细胞凋亡以及在体外预防化疗诱导的角质形成细胞凋亡的能力。
给裸鼠每日喂食不同剂量的CsA(10 - 100毫克/千克)。对背部皮肤切片进行苏木精和伊红染色,随后用4-脱氧溴尿苷进行免疫染色,以检测毛囊数量和毛囊角质形成细胞增殖情况。分离毛囊角质形成细胞并检测其凋亡状态。用4-氢过氧环磷酰胺在角质形成细胞系中体外诱导凋亡。通过膜联蛋白-V/碘化丙啶结合法测定不同浓度CsA(0.1 - 5微克/毫升)的抗凋亡作用。
CsA使毛囊数量呈剂量依赖性增加,但对毛囊角质形成细胞增殖无影响。CsA治疗可减少凋亡毛囊角质形成细胞的数量。在体外,CsA对处理过的角质形成细胞早期和晚期凋亡程度有剂量依赖性抑制作用。
CsA可能通过增加毛囊数量和抑制毛囊角质形成细胞凋亡来诱导毛发增多,从而延缓毛囊退化。