平目汤对格雷夫斯眼病小鼠眼球后脂肪细胞凋亡的影响

Effects of Pingmu Decoction on apoptosis of retrobulbar adipocytes in mice with Graves’ ophthalmopathy

目的探讨平目汤对格雷夫斯眼病小鼠模型眼球后脂肪细胞凋亡的影响及作用机制。方法 BALB/c雌性小鼠随机分为模型组和平目汤低、中、高剂量组,每组15只。采用hTSHR重组质粒免疫BALB/c雌性小鼠建立格雷夫斯眼病小鼠模型。造模成功后,平目汤低、中、高剂量组分别按照7.75 g·kg^-1·d^-1 、15.5 g·kg^-1·d^-1 、31 g·kg^-1·d^-1 生药量灌胃干预,共灌胃8周。观察小鼠眼球后脂肪细胞凋亡情况,以及眼球后脂肪细胞Bax、Bcl-2、Fas、Fasl、Chop、Caspase-12 mRNA及蛋白表达情况。结果与模型组比较,平目汤各组眼球后脂肪细胞凋亡率均升高(P<0.05);除平目汤高剂量组Caspase-12 mRNA外,其余各组Bax、FasL、Chop、Caspase-12 mRNA及蛋白表达水平均升高(P<0.05),以平目汤中剂量组更为明显。结论平目汤可有效促进格雷夫斯眼病小鼠眼球后脂肪细胞的凋亡,其凋亡途径可能为线粒体途径、死亡受体途径与内质网途径共同作用。

Objective To investigate the effects of Pingmu Decoction on apoptosis of retrobulbar adipocytes in a mouse model of Graves’ ophthalmopathy and the mechanism of action. Methods Female BALB/c mice were randomly divided into model group and low-, medium-and high-dose Pingmu Decoction groups, 15 animals in each group. A mouse model of Graves’ ophthalmopathy was established by immunizing the female BALB/c mice with hTSHR recombinant plasmid. After successful modeling, the low-, medium-and high-dose Pingmu Decoction groups were given crude drug at 7.75 g·kg^-1·d^-1, 15.5 g·kg^-1·d^-1 and 31 g·kg-1·d-1 respectively by gavage for 8 weeks. Apoptosis of retrobulbar adipocytes was observed, and the expression of Bax, Bcl-2, Fas, Fasl, Chop, Caspase-12 mRNA and protein of the cells was detected in mice. Results Compared with the model group, the apoptotic rate of retrobulbar adipocytes increased in the Pingmu Decoction Groups(P<0.05). Except for Caspase-12 mRNA in the high-dose Pingmu Decoction group, the expression of Bax, FasL, Chop and Caspase-12 mRNA and protein increased in the remaining groups(P<0.05), even more evident in the medium-dose Pingmu Decoction group. Conclusion Pingmu Decoction promotes apoptosis of retrobulbar adipocytes in mice with Graves’ ophthalmopathy, and the apoptotic pathway may be the combined action of the mitochondrial pathway, death receptor pathway and endoplasmic reticulum pathway.