基于AR/SREBP-1/ACC1信号通路探讨雄激素诱导金黄地鼠皮脂代谢异常的发病机制  

Mechanism of androgen induced abnormal lipid metabolism in golden hamster skin based on AR/SREBP-1/ACC1 signaling pathway

作　　者：任威威 薛兵 方惠敏 王迪 任艳青[1] 杨彩瑞 薛思思 成秀梅[1] REN Weiwei;XUE Bing;FANG Huimin;WANG Di;REN Yanqing;YANG Cairui;XUE Sisi;CHENG Xiumei(Hebei University of Chinese Medicine,Hebei Key Laboratory of Integrative Medicine on Liver Kidney Patterns,Shijiazhuang 050091,China)

机构地区：[1]河北中医学院,河北省肝肾病证研究重点实验室,石家庄050091

出　　处：《实用医学杂志》2020年第8期1010-1014,共5页The Journal of Practical Medicine

基　　金：河北省中医药管理局基金项目(编号:81373514)。

摘　　要：目的通过研究AR/SREBP-1/ACC1信号通路与雄激素诱导的皮脂代谢异常的关系来探讨痤疮的发病机制。方法采用天生具有雄激素依赖特性的雄性金黄地鼠为动物模型,设对照组和双氢睾酮(dihydrotesto-sterone,DHT)组,每组10只,两组金黄地鼠内耳廓分别用无水乙醇和0.1 mg/mL的DHT溶液进行干预。通过HE染色观察耳廓组织病理变化;油红O染色及比色法检测耳廓组织中游离脂肪酸(nonesterified free fatty acids,NEFA)、甘油三酯(TG)含量,分析金黄地鼠耳廓皮脂分泌情况;免疫组化和Western Blot检测金黄地鼠耳廓组织中雄激素受体(androgen receptor,AR)、胆固醇调节元件结合蛋白1(sterol regulatory element binding protein 1,SREBP-1)、乙酰辅酶A羟化酶1(acetyl coenzyme A carboxylase 1,ACC1)蛋白表达水平,探讨皮脂代谢与AR/SREBP-1/ACC1信号通路的关系。结果与对照组比较,DHT组耳廓皮脂腺组织腺叶增大,排列更加紧密,NEFA和TG分泌增多(均P<0.01),免疫组化结果显示AR、SREBP-1、ACC1阳性表达均升高(P<0.05,P<0.01),Western Blot结果显示AR、SREBP-1、ACC1蛋白表达均升高(均P<0.01)。结论雄激素通过AR/SREBP-1/ACC1信号通路的过度激活,使NEFA和TG分泌增多,其可能是痤疮形成的重要发病机制。Objective To explore the pathogenesis of acne by studying the relationship between AR/SREBP 1/ACC1 signaling pathway and androgen induced abnormal lipid metabolism in the skin.Methods The male golden hamster was used as the animal model because of its natural androgen dependence.The control group and DHT group were set up with 10 golden hamsters in each group.The ventral sides of the ears of the golden ham ster in the two groups were intervened with anhydrous ethanol and 0.1 mg/mL dihydrotestosterone(DHT)solution respectively.The pathological changes of auricle were observed by hematoxylin and eosin stain(HE),the content of nonesterified free fatty acids(NEFA)and triglyceride(TG)in ear tissue was detected by oil red O staining and colorimetry,and the lipid secretion of ear skin was analyzed.The expression of androgen receptor(AR),sterol regulatory element binding protein 1(SREBP 1)and acetyl coenzyme A carboxylase 1(ACC1)were detected by immunohistochemistry and Western Blot.The relationship between lipid metabolism and AR/SREBP 1/ACC1 signal ing pathway were studied.Results Compared with the control group,the gland lobes of the sebaceous glands of the ears in DHT group were enlarged and arranged more closely,the secretion of NEFA and TG were increased(P<0.01),the expression of AR,SREBP 1 and acc1 were increased detected by immunohistochemistry(P<0.05,P<0.01),and the expression of AR,SREBP-1 and acc1 were increased detected by Western Blot(P<0.01).Conclusion Androgen can increase the secretion of NEFA and TG through AR/SREBP-1/ACC1 signaling path way,which may be an important pathogenesis of acne.

关 键 词：痤疮 皮脂代谢 雄激素受体(AR) 胆固醇调节元件结合蛋白1(SREBP-1) 乙酰辅酶A羟化酶1(ACC1)R34 

分 类 号：R34[医药卫生—基础医学]