摘要目的 观察Bmi-1基因对小鼠颌下腺形态与功能的影响,以期研究Bmi-1基因对小鼠颌下腺的增殖与衰老的作用.方法 利用组织学、组织化学及蛋白质印迹法比较分析4周龄12只雄性野生型小鼠(WT)和12只雄性Bmi-1基因敲除小鼠(Bmi-1-/-)颌下腺的重量、唾液分泌、形态、衰老与增殖能力等方面的表型差异.结果 颌下腺重量/体质量比WT小鼠[(1.89±0.15)μg]与Bmi-1-/-[(1.34±0.07) μg]比较,差异有统计学意义(P=0.003);单位体质量静态唾液总流率WT[(0.21±0.02) μg/rnin]及Bmi-1-/-[(0.10±0.02) μg/min]比较,Bmi-1-/-明显降低,差异有统计学意义(P=0.001);Bmi-1-/-颌下腺导管增多、颗粒曲管较明显、管径细、分支少;衰老相关的β-gal染色阳性细胞数增加(WT:0.00,Bmi-1-/-:0.18 ±0.02);此外,细胞增殖相关指标Ki-67阳性细胞百分率降低(WT:0.40 ～0.47,Bmi-1-/-:0.18 ～0.20)(P=0.000);蛋白质印迹法显示细胞周期蛋白p16(WT:1.00±0.12,Bmi-1-/-:0.00 ±0.00)(P =0.003)、蛋白质印迹方法p19(WT:0.97 ±0.09,Bmi-1-/-:5.09±0.21)(P=0.004)表达水平升高.结论 Bmi-1基因缺失可导致小鼠颌下腺呈衰老表型,功能异常.

abstractsObjective To determine the role of Bmi-1 in the submandibular gland (SMG) of mice.Methods SMG of 4-week wild-type(WT) and Bmi-1 null(Bmi-1-/-) mice was analyzed on the weight,salivary flow rate,hematoxylin-eosin staining morphological differences and the changes in proliferation and aging by histology,immunohistochemistry and Western blotting.Results Compared with WT mice,the average static salivary flow rate [WT:(0.21 ±0.02) μg/min,Bmi-1-/-:(0.10 ±0.02) μg/min] (P =0.001) and the submandibular gland weight [WT:(1.89 ± 0.15) μg],Bmi-1-/-:[(1.34 ± 0.07) μg] (P =0.003) of the male Bmi-1-/-mice were significantly decreased,the number of gland duct increased,and the granular convoluted duct showed reduced diameter and branches.More senescence-associated β-galactosidase positive cells existed in SMG of Bmi-1-/-mice (WT:0.00,Bmi-1-/-:0.18 ± 0.02),and Ki-67 immunopositive cells decreased in SMG of Bmi-1-/-mice(WT:0.40 ～ 0.47,Bmi-1-/-:0.18 ～ 0.20) (P =0.000).The expression of p16 (WT:1.00 ± 0.12,Bmi-1-/-:0.00 ±0.00) (P =0.003) and p19(WT:0.97 ±0.09,Bmi-1-/-:5.09 ±0.21) (P =0.004) were up-regulated dramatically in SMG of the Bmi-1-/-mice.Conclusions Bmi-1 gene deficiency causes abnormal function of SMG by inducing senescence phenotype of SMG.