目的探讨完全弗氏佐剂(CFA)诱导胸腺细胞凋亡对NOD鼠1型糖尿病的预防作用。方法42只3周龄NOD雌鼠随机均分为CFA组和PBS组(n=21),分别给予NOD鼠后足板一次性注射CFA50μl、磷酸盐缓冲液(PBS)50μl,于6、12周(各取5只小鼠)及30周(11只小鼠)时观察胰岛β细胞凋亡、胸腺细胞凋亡、胰岛炎程度和糖尿病发病率。结果与PBS组相比,6周、12周时CFA组胰岛炎积分明显降低(P〈0.01),胰岛β细胞凋亡率明显减少(P〈0.01),而经地塞米松诱导可见更多的胸腺细胞凋亡(P〈0.01)。6周、12周时胰岛炎积分与β细胞凋亡率呈正相关(r=0.511,P〈0.05),与胸腺淋巴细胞凋亡率呈负相关(r=-0.549,P〈0.05);β细胞凋亡率与胸腺淋巴细胞凋亡率呈负相关(r=-0.614,P〈0.01)。30周时,CFA组糖尿病发病率为9.1%(1/11),而PBS组糖尿病发病率为81.8%(9/11),两组间差异具有统计学意义(P=0.001)。结论CFA可通过调节胸腺细胞凋亡,导致胰岛β细胞凋亡的减少,可能是减轻NOD鼠胰岛炎并预防1型糖尿病的机制之一。
Objective To investigate the preventive effect of complete Freunds adjuvant induced thymocyte apoptosis on NOD mice with type 1 diabetes. Methods Forty two female NOD mice of 3 weeks old were randomly divided into complete Freunds adjuvant group (CFA) and phosphate buffer saline group (PBS) (21 each). Animals of CFA group received injection of 50pd CFA at hind foot-pad, and those in PBS group received 50μl PBS at the same location. Five mice of each group were sacrificed at the 6th and 12th week, respectively, and the remainders of each group were sacrificed at the 30th week for the examination of insular 13 cell apoptosis, thymocytes apoptosis, insulitis severity and diabetes incidence. Results Both the insulitis severity score and the 13 cell apoptosis declined ( P〈0. 05, P〈0. 01), while the thymocyte apoptosis increased (P〈0. 01), in CFA group than in PBS group at the 6th and 12th week, respectively. Positive correlation was found between the apoptotic rates of insular 13 cells and the insulitis severity scores at the 6th and 12th week (r=0. 511, P〈2 0.05) ; while negative correlation was also found not only between insulitis severity scores and the thymocyte apoptotic rates at the 6th and 12th week (r=-0. 549,P〈0. 05), but also between the apoptotic rates of 13 cells and the thymocyte apoptotic rates (r= -0. 614, P〈 0. 01). At the 30th week, the incidence of diabetes was 9. 1% (1/11) in CFA group and 81.8% (9/11) in PBS group. Obviously, the diabetes incidence in CFA group was much lower than that in PBS group (P=0. 001). Conclusion By regulating the thyrmcyte apoptosis, CFA may suppress the insular β cell apoptosis, extenuate the insnlitis severity and prevent the development of autoimmune diabetes in NOD mice.