环孢素A对小鼠牙龈上皮细胞凋亡的影响

Effects of cyclosporin A on apoptosis of gingival keratinocytes in mice

目的探讨环孢素A(CsA)导致牙龈上皮增厚的机制。方法选取美国癌症研究所(ICR)雄性小鼠,随机均分为实验(T)组和对照(C)组。T组胃饲30 mg/(kg.d)的CsA橄榄油溶液,C组仅给橄榄油。给药1、2、4、6周后处死小鼠,取下颌前牙牙龈及腭中部黏膜组织标本,制备切片。用末端转移酶介导的三磷酸脱氧尿苷缺口末端标记实验(TUNEL)检测牙龈上皮的口腔龈上皮、龈缘-沟内上皮和腭黏膜上皮细胞凋亡率。结果T组1、2周时,龈缘-沟内上皮细胞凋亡率显著降低,且TUNEL阳性细胞主要分布于上皮表层,棘层和基底层少见,而C组阳性细胞则可见于牙龈上皮各层;4、6周时两凋亡率无明显变化。各观察时间,小鼠口腔龈上皮细胞和腭黏膜上皮细胞凋亡率改变无统计学差异。结论CsA早期对小鼠牙龈上皮细胞调亡有明显抑制作用,提示其诱导小鼠牙龈上皮增生早期可能与牙龈上皮细胞的凋亡抑制有关。

Objective To investigate the mechanism of cyclosporin A（CsA）-induced murine gingival epithelial hyperplasia. Methods 6- week-old male, ICR mice received CsA dissolved in olive oil （30 mgCsA/kg body weight） daily through gastric feeding. Mice were chosen randomly to sacrifice after 1, 2, 4, 6 wk, respectively. 4 μm serial longitudinal-sections were processed in the gingivae of central incisors and the palatal mucosa, then determined the apoptotic rates of the keratinocytes in such parts as oral epithelium （OE）, oral sulcular epithelium （OSE） of gingivae and palatal mucosa by in situ TUNEL assay. Results After 1 and 2 wk, the apoptotic rates of keratinocytes in OSE were significantly decreased in the test group while there were no statistical differences between the two groups after 4 wk and 6 wk. Moreover, TU^EL-positive cells were mainly seen in the superficial layers in the test group, whereas in the inner being they were also seen in the control. And there were no significant changes in the percentages of apoptotic epithelia in OE and palatal mucosa at any observation time. Conclusion CsA can inhibit the apoptosis of keratinocytes in OSE at early time. This indicates that the mechanism of CsA - induced gingival epithelial overgrowth may be associated with its inhibiting apoptosis of keratinocytes in OSE.