Nitric Oxide Scavenging and Hydrogen Sulfide Production Synergistically Treat Rheumatoid Arthritis
作者全名："Geng, Wenbo; Liu, Xuezhe; Tao, Bailong; He, Ye; Li, Ke; Gao, Pengfei; Feng, Qian; Zhao, Peng; Luo, Zhong; Cai, Kaiyong"
作者地址："[Geng, Wenbo; Liu, Xuezhe; Li, Ke; Gao, Pengfei; Feng, Qian; Zhao, Peng; Cai, Kaiyong] Chongqing Univ, Minist Educ, Key Lab Biorheol Sci & Technol, Coll Bioengn, Chongqing 400044, Peoples R China; [Tao, Bailong] Chongqing Med Univ, Lab Res Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [He, Ye] Duke Univ, Thomas Lord Dept Mech Engn & Mat Sci, Durham, NC 27708 USA; [Luo, Zhong] Chongqing Univ, Sch Life Sci, Chongqing 400044, Peoples R China"
通信作者："Zhao, P; Cai, KY (通讯作者)，Chongqing Univ, Minist Educ, Key Lab Biorheol Sci & Technol, Coll Bioengn, Chongqing 400044, Peoples R China."
来源：ADVANCED HEALTHCARE MATERIALS
文献类型：Article; Early Access
关键词：H2S; inflammation; NO; rheumatoid arthritis; synergistic treatment
摘要："To restore the disordered endogenous gas levels is an efficient alternative for the treatment of rheumatoid arthritis (RA). Both insufficient hydrogen sulfide (H2S) and excessive nitric oxide (NO) contribute to synovial inflammation. Herein, a new block polymer PEG(10)-b-PNAPA(30)-b-PEG(10) composed of an NO-responsive monomer and a cysteine-triggered H2S donor, which can simultaneously scavenge NO and release therapeutic H2S for RA treatment, is reported. In vitro experiments demonstrate that the polymer exhibits a synergistic effect on suppressing reactive oxygen species levels and pro-inflammatory cytokine production via NF-kappa B signaling pathway. It leads to the polarization of macrophages from M1 to M2 phenotype. Moreover, the released H2S further restrains NO production by suppressing the expression of iNOS. In vivo experiments with an RA rat model show that the system markedly mitigates the synovial inflammation, osteoporosis, and clinical symptoms of RA rats, which is attributed to the combination therapy of H2S release and NO depletion. This work provides new insight into the synergistic treatment of RA and endogenous gas-related diseases."
基金机构："National Natural Science Foundation of China [51825302, 21734002, 52021004, 82102225]; Natural Science Foundation of Chongqing [cstc2021jcyj-cxttX0002]; Fundamental Research Funds for the Central Universities [2021CDJQY-057, 2022CDJXY-026]; [SYXK-PLA-20120031]"
基金资助正文："All animal procedures were approved by the Animal Ethics Committee of Third Military Medical University (SYXK-PLA-20120031). This work was financially supported by National Natural Science Foundation of China (51825302, 21734002, 52021004, and 82102225), Natural Science Foundation of Chongqing (cstc2021jcyj-cxttX0002), and Fundamental Research Funds for the Central Universities (2021CDJQY-057 and 2022CDJXY-026)."