胰高血糖素样肽-1通过抑制核因子κB信号通路减轻血管周围脂肪组织中NLRP3炎性小体依赖性炎症。
GLP-1 alleviates NLRP3 inflammasome-dependent inflammation in perivascular adipose tissue by inhibiting the NF-κB signalling pathway.
作者信息
Chen Xiangheng, Huang Qiuling, Feng Juling, Xiao Zhongsheng, Zhang Xiaoling, Zhao Lei
机构信息
Department of Gastrointestinal Surgery, The First Affiliated Hospital, University of South China, Hengyang, China.
Research Lab of Translational Medicine, Heng Yang Medical School, University of South China, Hengyang, China.
出版信息
J Int Med Res. 2021 Feb;49(2):300060521992981. doi: 10.1177/0300060521992981.
OBJECTIVES
To study the effect of glucagon-like peptide 1 (GLP-1) on NLR family pyrin domain containing 3 (NLRP3) inflammasome-induced inflammation in perivascular adipose tissue (PVAT) of Zucker diabetic fatty (ZDF) rats and the underlying role of nuclear factor (NF)-κB signalling.
METHODS
Thirty ZDF rats were randomly divided into three study groups: DM (0.9% saline, subcutaneously); DM+GLP-1 (liraglutide, s.c.); and NF-κB+GLP-1 (betulinic acid then liraglutide, s.c.). Ten Zucker lean rats were examined as normal controls. PVAT from ZDF (DM) rats was examined for inflammasome mRNA. Protein levels of NLRP3, cleaved caspase-1, caspase-1, gasdermin D (GSDMD), interleukin (IL)-1β and IL-18 in PVAT were compared between control, DM and DM+GLP-1 groups. Protein levels of NLRP3, IL-1β, IL-18 and NF-κB in PVAT were compared between control, DM, DM+GLP-1 and NF-κB+GLP-1 groups.
RESULTS
The inflammasome most abundantly expressed in ZDF rat PVAT was . NLRP3, cleaved caspase-1, IL-1β, IL-18, and GSDMD were markedly upregulated in DM versus control tissue, and GLP-1 reversed this effect. Inhibition of NLRP3 inflammasome-associated inflammation by GLP-1 was lost by activation of NF-κB with betulinic acid.
CONCLUSION
GLP-1 may alleviate NLRP3 inflammasome-dependent inflammation in PVAT by inhibiting NF-κB signalling.
目的
研究胰高血糖素样肽1（GLP-1）对 Zucker 糖尿病脂肪（ZDF）大鼠血管周围脂肪组织（PVAT）中含 NOD 样受体蛋白 3（NLRP3）炎性小体诱导的炎症的影响以及核因子（NF）-κB 信号传导的潜在作用。
方法
将 30 只 ZDF 大鼠随机分为三个研究组：糖尿病组（皮下注射 0.9%生理盐水）；糖尿病+GLP-1 组（皮下注射利拉鲁肽）；NF-κB+GLP-1 组（先皮下注射桦木酸，然后皮下注射利拉鲁肽）。将 10 只 Zucker 瘦大鼠作为正常对照进行检查。检测 ZDF（糖尿病）大鼠 PVAT 中的炎性小体 mRNA。比较对照组、糖尿病组和糖尿病+GLP-1 组 PVAT 中 NLRP3、裂解的半胱天冬酶-1、半胱天冬酶-1、gasdermin D（GSDMD）、白细胞介素（IL）-1β和 IL-18 的蛋白水平。比较对照组、糖尿病组、糖尿病+GLP-1 组和 NF-κB+GLP-1 组 PVAT 中 NLRP3、IL-1β、IL-18 和 NF-κB 的蛋白水平。
结果
在 ZDF 大鼠 PVAT 中表达最丰富的炎性小体是 。与对照组织相比，糖尿病组中 NLRP3、裂解的半胱天冬酶-1、IL-1β、IL-18 和 GSDMD 明显上调，而 GLP-1 逆转了这种作用。用桦木酸激活 NF-κB 可消除 GLP-1 对 NLRP3 炎性小体相关炎症的抑制作用。
结论
GLP-1 可能通过抑制 NF-κB 信号传导减轻 PVAT 中 NLRP3 炎性小体依赖性炎症。
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