脂联素抑制炎症小体NLRP3表达减轻高糖高脂诱导内皮细胞损伤

Adiponectin decreases endothelial cell injury by inhibiting expression of NLRP3 inflammasome

目的研究脂联素(APN)是否通过抑制炎症小体NLRP3表达减轻高糖高脂所致的内皮细胞损伤。方法将培养的人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)分为6组:对照组、高糖高脂组、对照+NLRP3 siRNA组,高糖高脂组+NLRP3 siRNA组,对照+APN组,高糖高脂+APN组。培养48 h后检测细胞存活率、凋亡率、炎症小体NLRP3表达水平。结果与对照组相比,高糖高脂组细胞存活率显著下降,细胞凋亡显著升高,炎症小体NLRP3表达水平显著升高(均P<0.05);炎症小体NLRP3 siRNA可有效的抑制炎症小体NLRP3的表达,改善高糖高脂引起的内皮细胞损伤(均P<0.05);APN能抑制高糖高脂引起的炎症小体NLRP3表达增多,进而减轻高糖高脂引起的内皮损伤(均P<0.05)。结论炎症小体NLRP3表达增多是高糖高脂诱导人脐静脉内皮细胞凋亡的内在机制,而脂联素可以通过抑制炎症小体NLRP3的过度表达发挥内皮保护作用。

AIM To investigate whether adiponectin （APN） exerts endothelial protection in response to high glucose/high-fat damage through inhibiting expression of NLRP3 inflammasome. METHODS Cultured human umbilical vein endothelial cells （HUVECs） were randomly divided into control group （5 mmoL/L glucose, 20 mmol/L mannitol, 48 h incubation）, high glucose/high-fat group （25 mmol/L glucose, 500 p^mol/L sodium palmitate, 48 h incubation ）, control ＋ siRNA group （5 mmoL/L glucose, 20 mmol/L mannitol and NLRP3 specific siRNA, 48 h incubation）, high glucose/high fat ＋ siRNA group （25 mmol/L glucose, 500 ~moL/L sodium palmitate and NLRP3 specific siRNA, 48 h incubation） , control ＋ APN group （5 mmol/L glucose, 20 mmol/L mannitol and 2 p,g/ml APN, 48 h incubation） and high glucose/ high-fat ＋ APN group （25 mmol/L glucose, 500 p, mol/L sodium palmitate and 2 p,g/ml APN, 48 h incu- bation）. Cells from these groups were harvested for evaluation of cell viability, apoptosis rate and NLRP3 inflammasome expression. RESULTS Compared with control group, cell viability decreased, and NLRP3 inflammasome expression and apoptosis rate increased in high glucose/high-fat group （all P 〈 0. 05 ）. These changes were all reversed by NLRP3 specific siRNA and APN （ all P 〈 0. 05）. CONCLUSION High glucose/high fat leads to increased expression of NLRP3 inflammasome, thereby causing cell injury in HUVECs. APN can protect HUVECs by inhibiting expression of the NLRP3 inflammasome.