三氧化二砷对MRL-lpr狼疮肾炎小鼠淋巴细胞凋亡及相关基因的影响

目的通过检测淋巴细胞凋亡比例、凋亡相关基因表达的变化情况,探讨三氧化二砷对MRL-lpr狼疮肾炎小鼠淋巴细胞凋亡的影响。方法14只MRL-lpr小鼠,随机分为两组,实验组用三氧化二砷隔日腹腔注射,对照组用生理盐水,疗程结束后检测两组小鼠抗双链DNA抗体水平、用流式细胞仪检测两组小鼠脾脏淋巴细胞凋亡情况、逆转录-聚合酶链反应检测基因caspase-3的表达水平及蛋白印记法测bcl-2的蛋白表达。结果实验组抗双链DNA抗体水平显著低于对照组,脾脏淋巴细胞凋亡较对照组明显增多,caspase-3水平亦明显增高,而bcl-2表达减少。结论三氧化二砷能够诱导MRL-lpr狼疮肾炎小鼠自身反应性淋巴细胞发生凋亡,其作用机制可能与激活caspase家族成员、抑制bcl-2等自身基因表达有关。

Effects of arsenic trioxide on lymphocyte apoptosis and its related genes in MRL-lpr mice with lupus nephritis

Objective To investigate the effects of arsenic trioxide on lymphocyte apoptosis in MRL-lpr mice with lupus nephritis, through the observation of apoptotic lymphocytes and gene expression relating to apoptosis. Methods Fourteen MRL-lpr mice were randomly assigned into experimental group or control group. Mice in experimental group were treated with arsenic trioxide and those in control group with saline. Mouse anti-dsDNA antibody titer was detected by ELISA. Apoptotic lymphocytes in spleen were assessed by flow cytometry. Caspase-3 expression was measured by RT-PCR, and bcl-2 expression by western blot. Results Anti-dsDNA antibody titer was significantly lower in experimental group than in control group. More apoptotic cells were found in spleen from mice of experimental group. Caspase-3 RNA was significantly higher in experimental group than in control group, but bcl-2 protein was less in experimental group. Conclusion Arsenic trioxide induces apoptosis of autoimmune lymphocytes in MRL- lpr mice with lupus nephritis, probably through the activation of caspase family and the inhibition of bcl-2 expression.