平目汤对Graves眼病造模小鼠球后脂肪组织及眼球后脂肪细胞Bax、Bcl-2、Fas、FasL mRNA表达量的影响

Effects of Pingmu Decoction(平目汤)on Adipose Tissue in Eyeballs and Thyroid Morphology and Expressions of Bax,Bel-2,Fas and FasL in Mice with Graves Ophthalmopathy

目的研究平目汤对Graves眼病模型小鼠球后脂肪组织及甲状腺的形态学影响。方法选用180只6周龄BALB/c雌性小鼠,随机分为6组,30只留为空白组,150只造模。通过平目汤不同剂量及地塞米松灌胃28 d,观察各组小鼠眼球后脂肪组织占眼球重量百分比、甲状腺与眼球组织病理及眼球后脂肪细胞Bax、Bcl-2、Fas、FasL mRNA的表达量。结果与模型组相比,平目汤不同剂量与地塞米松干预后眼球后脂肪组织占眼球重量百分比均下降(P<0.05);平目汤低、中、高剂量组BALB/c小鼠眼球后组织病理可见脂肪堆积均较空白组多,较模型组少,脂肪细胞数量减少,单个脂肪细胞截面积增大,淋巴细胞浸润减少,地塞米松组BALB/c小鼠眼球后组织病理可见大量脂肪堆积,伴有大量淋巴细胞浸润,脂肪堆积较空白组与平目汤干预组显著;平目汤不同剂量组小鼠甲状腺滤泡较空白组增大,与模型组大小相仿,部分滤泡腔内物质吸收。滤泡腔可见有数量不等的淋巴细胞浸润,浸润程度较空白组多,较模型组少;与模型组及地塞米松组相比,平目汤低、中、高剂量组Bax mRNA相对表达量均升高;平目汤3组表达量由低到高依次为:平高组<平低组<平中组,相互间均有统计学意义;与模型组相比,其余各组眼球后脂肪细胞Bcl-2 mRNA略有下降,各组间相互间无统计学意义;与模型组相比,其余各组眼球后脂肪细胞Fas mRNA略有升高,各组间相互间无统计学意义;与模型组及地塞米松组相比,平目汤低、中、高剂量组FasL mRNA相对表达量均升高,平目汤不同剂量之间相互比较均无统计学意义。结论平目汤可通过促进球后治疗细胞的凋亡有效抑制Graves眼病小鼠球后脂肪积聚,并改善甲状腺炎性反应,凋亡途径可能是死亡受体途径与线粒体途径的共同作用。

Objective To study the effects of Pingmu Decoction(平目汤) on the adipose tissue in the eyeballs and the thyroid morphology in mice with Graves ophthalmopathy.Methods A total of 180 female mice aged 6 weeks old were randomly divided into six groups and 150 of them were selected to establish the model of graves ophthalmopathy.The mice were intervened by Pingmu Decoction different doses and dexamethasone for 28 days.Then we observed the percentage of adipose tissue in the eyeballs and the histopathology of the thyroid and posterior eye and the expressions of Bax,Bcl-2,Fas and FasL in retrobulbar adipocytes.Results After the intervention,the percentage of the groups were different: blank group < middle dose group of Pingmu Decoction <low dose group of Pingmu Decoction < dexamethasone group < high dose group of Pingmu Decoction < model group.The percentage of weight of the adipose tissue in the eyeball after the different doses of Pingmu Decoction and dexamethasone decreased compared with the model group(P < 0.05).There was a significant decrease in middle and low dose groups of Pingmu Decoction compared with dexamethasone group and high dose group of Pingmu Decoction(P < 0.05).The thyroid tissue HE staining: model group can be seen thyroid lymphocyte infiltration,interstitial hyperplasia significantly.Pingmu Decoction reduced the infiltration of thyroid lymphocytes after different doses of intervention.The thyroid can be seen a small amount of lymphocyte infiltration after dexamethasone treatment.The tissue after the eye ball was stained with HE.Compared with the model group,each group of Pingmu decoction eye tissue adipose tissue accumulation less.There was no significant change in dexamethasone group.Compared with model group and dexamethasone group,the relative expression of Bax mRNA in low,medium and high dose groups of Pingmu Decoction increased;the expression of Bax mRNA in Pingmu Decoction group from low to high was as follows: Pingmu Decoction group < Pingmu Decoction group < Pingzhong group,there were significant differences among them;compared with model group,the expression of Bcl-2 in retrobulbar adipocytes of the other groups decreased slightly,and each group decreased slightly.There was no statistical difference between the two groups.Compared with the model group,Fas gene expression in retrobulbar adipocytes in the other groups increased slightly,but there was no statistical difference among the groups.Compared with the model group and dexamethasone group,the relative expression of FasL gene in the low,middle and high dose groups of Pingmu Decoction increased,and the different doses of Pingmu Decoction were compared with each other.There was no statistical difference.Conclusion Pingmu Decoction can effectively inhibit retrobulbar fat accumulation and improve thyroid inflammatory response by promoting apoptosis of retrobulbar cells in Graves ophthalmopathy mice.Apoptotic pathway may be a combination of death receptor pathway and mitochondrial pathway.