硫化氢通过ADAM17调节脂肪细胞中sFlt-1生成的实验研究  

Experimental study of regulatory effect of hydrogen sulfide on sFlt-1 production in adipocytes through ADAM17

作　　者：胡天晓[1] 王钢[2] 谭擎缨[1] 阮芸[1] 王秀景[1] 姚佳琦[1] 许瑶[1] 王静[1] Hu Tianxiao, Wang Gang, Tan Qingying, Ruan Yun, Wang Xiujing, Yao Jiaqi, Xu Yao, Wang Jing(Department of Endocrinology, Chinese PLA 11th Hospital, Hangzhou 310013, China)

机构地区：[1]解放军第一一七医院内分泌科,杭州310013 [2]第二军医大学生理学教研室,上海200433

出　　处：《中华内分泌代谢杂志》2018年第9期784-789,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金青年项目（81701481）;南京军区医学科技创新经费资助项目（重大专项,14ZX30）

摘　　要：目的 研究硫化氢通过解整合素-金属蛋白酶 17 （ a distintegrin and metalloproteinase 17, ADAM17）对脂肪细胞中可溶性fms样酪氨酸激酶1（ soluble fms-like tyrosine kinase 1, sFlt-1）生成的调节作用.方法 培养3T3-L1细胞株并诱导分化为脂肪细胞,用不同剂量的硫氢化钠（ NaHS）、L-半胱氨酸处理或转染胱硫醚-γ-裂解酶（cystathionine-γ-lyase, CSE）的siRNA、ADAM17的siRNA或用ADAM17的抑制剂、单克隆抗体处理.处理24 h后,测定细胞中ADAM17、CSE的表达量以及sFlt-1的生成量.结果 10、25、50 nmol/L NaHS或0.5、1.0、2.0 μmol/L L-半胱氨酸处理后脂肪细胞中ADAM17的表达量及sFlt-1的生成量均显著降低,且NaHS、L-半胱氨酸剂量越大,细胞中ADAM17的表达量及sFlt-1的生成量越低;转染CSE的siRNA后,2.0 μmol/L L-半胱氨酸减少脂肪细胞中ADAM17的表达及sFlt-1的生成的效应被逆转;转染ADAM17 siRNA或用ADAM17抑制剂及单克隆抗体处理后,脂肪细胞中sFlt-1的生成量均显著降低.结论硫化氢能够通过下调ADAM17的表达来减少脂肪细胞中sFlt-1的生成.Objective To study the effect of hydrogen sulfide on the production of soluble fms-like tyrosine kinase 1 （sFlt-1） through a distintegrin and metalloproteinase 17 （ADAM17） in adipocytes. Methods 3T3-L1 cells were cultured and induced to differentiate into adipocytes, then treated with different doses of sodium hydrogen sulfide （NaHS）, L-cysteine or transfected with cystathionine-γ-lyase （ CSE） siRNA, ADAM17 siRNA or treated with ADAM17 inhibitor, monoclonal antibody. 24 hours after treatment, the expression of ADAM17, CSE, and the production of sFlt-1 were determined. Results After the treatment of 10, 25, 50 nmol/L NaHS or 0. 5, 1. 0, 2. 0 μmol/L L-cysteine, the expression of ADAM17 and the production of sFlt-1 in adipocytes were significantly decreased, the higher dose of L-cysteine and sFlt-1, the lower expression of ADAM17 and the production of sFlt-1; the effect of 2.0 μmol/L L-cysteine decreasing the expression of ADAM17 and the production of sFlt-1 were reversed by transfection of CSE siRNA; after the transfection of ADAM17 siRNA and treatment of ADAM17 inhibitor or monoclonal antibody, the production of sFlt-1 in adipocytes were significantly decreased. Conclusion Hydrogen sulfide can reduce the production of sFlt-1 in adipocytes by downregulating the expression of ADAM17.

关 键 词：肥胖 脂肪细胞 硫化氢 ADAM17 SFLT-1 

分 类 号：R587.2[医药卫生—内分泌]