Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLR family pyrin domain containing 3 (NLRP3) inflammasome in diabetic rats
硫酸乙酰肝素在糖尿病大鼠中通过下调NLRP3炎症小体抑制炎症反应并促进伤口愈合
Abstract
enBackground
Heparan sulfate (HS) attenuates the inflammatory response and improves diabetic wound healing in rats. However, the specific mechanisms by which HS suppresses inflammation are not clear. Given that NLR family pyrin domain containing 3 (NLRP3) is a major receptor involved in innate immune regulation, the aim of the present study was to elucidate the effects of HS on NLRP3 and proinflammatory cytokines in diabetic wounds.
Methods
Full-thickness wounds were created on the back of diabetic rats. The experimental group received HS treatment (1 mg/kg, i.m., on Days 0 and 7), whereas the control group received vehicle (0.1% dimethylsulfoxide in 0.9% NaCl). Expression of NLRP3 and its downstream effector molecules, namely cleaved interleukin (IL)-1β, IL-18, tumor necrosis factor (TNF)-α, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), proteinase inhibitor 9, and caspase-12, in the wound tissues was examined.
Results
Treatment with HS accelerated wound healing in diabetic rats. Rats treated with HS exhibited decreased activation of cleaved IL-1β, IL-18, and TNF-α, as well as decreased expression of NLRP3 and ASC. In addition, HS increased levels of proteinase inhibitor 9 and caspase-12.
Conclusions
Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLRP3 inflammasome and cleaved IL-1β during the wound healing process in diabetic rats.
摘要
zh背景
硫酸乙酰肝素(heparan sulfate, HS)降低炎症反应并促进糖尿病大鼠的伤口愈合。然而其抑制炎症反应的具体机制仍不明确。NLRP3(NLR family pyrin domain containing 3)是固有免疫调节的主要受体, 本研究旨在阐明硫酸乙酰肝素对糖尿病伤口中的NLRP3及炎症因子表达的影响。
方法
在糖尿病大鼠的后背上制备伤口模型。试验组术后0天和7天时肌肉注射硫酸乙酰肝素治疗(1 mg/kg), 对照组接受生理盐水(0.1%二甲亚砜溶于0.9%的NaCl中)处理。检测伤口组织中NLRP3及其下游效应分子(包括IL-1β、IL-18、TNF-α、ASC、蛋白酶抑制剂-9以及Caspase-12)的表达水平。
结果
硫酸乙酰肝素能加速糖尿病大鼠的伤口愈合。试验组大鼠伤口组织中IL-1β、IL-18和TNF-α的活化水平下降, NLRP3和ASC的表达水平也下降, 同时, 硫酸乙酰肝素能提高蛋白酶抑制剂-9以及Caspase-12的表达水平。
结论
硫酸乙酰肝素在糖尿病大鼠伤口愈合的过程中, 通过抑制NLRP3炎性体以及活化IL-1β水平来抑制炎症反应并且促进伤口愈合。
