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目的:观察高糖刺激对人肾小球系膜细胞（HMC）A类清道夫受体（SR-A）表达的影响，并初步探讨SR-A介导HMC在高糖环境下发生炎症损伤的相关机制。方法:将体外培养的HMC按照其培养基中D-葡萄糖浓度分为正常糖组和高糖组（葡萄糖浓度分别为5.5 mmol/L和30 mmol/L），并以甘露醇组作为高渗对照，在高糖组瞬时转染SR-A小干扰RNA（siSR-A）并设置转染对照组（siNC）。运用蛋白免疫印迹法检测各组SR-A、核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）、白细胞介素（IL）1β蛋白含量，免疫荧光技术检测SR-A，实时荧光定量PCR检测各组NLRP3、半胱氨酸天冬氨酸特异性蛋白水解酶-1（Caspase-1）、IL-1β、纤连蛋白（FN）、Ⅳ型胶原（ColⅣ）、α-平滑肌肌动蛋白（α-SMA）、内质网应激标志物葡萄糖调节蛋白（GRP）78 基因mRNA，酶法检测Caspase-1相对活性，酶联免疫吸附法检测细胞培养基中IL-1β浓度，流式细胞术检测细胞周期。运用单因素方差分析和 SNK n q检验进行统计分析。n 结果:高糖组HMC中SR-A蛋白水平高于正常糖组和甘露醇组（1.23±0.21比0.68±0.10，1.23±0.21比0.78±0.13，均n P<0.05），高糖组SR-A蛋白平均荧光强度，NLRP3和IL-1β的蛋白水平，NLRP3、Caspase-1、IL-1β的 mRNA水平，Caspase-1相对活性和IL-1β浓度均高于正常糖组和甘露醇组（均n P<0.05）。沉默SR-A基因后，高糖siNC组SR-A蛋白水平高于高糖siSR-A组和正常糖siNC组（1.23±0.10比0.20±0.01，1.23±0.10比0.87±0.01，均n P<0.01）。高糖siNC组NLRP3、IL-1β蛋白水平和NLRP3、Caspase-1、IL-1β、FN、ColⅣ、α-SMA、GRP78 mRNA水平和HMC细胞周期中DNA合成期占比也均明显高于高糖siSR-A组和正常糖siNC组（均n P<0.05）。n 结论:高糖可以通过上调SR-A表达促进HMC异常增殖、系膜基质产生增加和发生氧化应激，加重细胞炎症损伤，这一过程可能与SR-A调节NLRP3-Caspase-1-IL-1β通路相关。“,”Objective:To investigate the effect of high glucose on scavenger receptor-A (SR-A) in human glomerular mesangial cells (HMC) and explore the mechanism of inflammatory injury mediated by SR-A in HMC cultured in high-glucose medium.Methods:According to the concentration of D-glucose in culture medium, HMC were divided into normal glucose group (5.5 mmol/L) and high glucose group (30 mmol/L), with mannitol group as hypertonic control. High glucose group was transfected with SR-A small interfering RNA (siSR-A) and the transfection control (siNC) group were set up. Western blotting technology was used to detect the levels of SR-A, NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-1β (IL-1β) protein. Immunofluorescent staining was applied to measure the SR-A in HMC. The mRNA of NLRP3, Caspase-1, IL-1β, FN, ColⅣ, α-SMA and GRP78 were detected by real-time quantitative PCR. The relative activity of Caspase-1 was detected by enzyme method and the concentration of IL-1β in culture medium was detected by enzyme linked immunosorbent assay. Flow cytometry was used to measure the cell cycles of HMC. One-way ANOVA and SNK-q test were used for statistical analysis.Results:The protein level of SR-A in high glucose group was higher than that in normal glucose group and mannitol group (1.23±0.21 n vs. 0.68±0.10, 1.23±0.21 n vs. 0.78±0.13, all n P<0.05). In addition, mean fluorescence intensity of SR-A, protein levels of NLRP3 and IL-1β, mRNA of NLRP3, Caspase-1 and IL-1β, relative activity of Caspase-1 as well as the concentration of IL-1β in high glucose group were all significantly higher than those in normal glucose group and mannitol group (alln P<0.05).After transfection induced silencing, SR-A protein in high glucose siNC group was higher than that in high glucose siSR-A group and normal glucose siNC group (1.23±0.10n vs. 0.20±0.01, 1.23±0.10 n vs. 0.87±0.01, all n P<0.01). In high glucose siNC group, the NLRP3, IL-1β proteins, the NLRP3, Caspase-1 and IL-1β mRNA, all of the mRNA levels of FN, ColⅣ, α-SMA, GRP78 and the proportion of DNA synthesis phase were all higher than those in high glucose siSR-A group and normal glucose siNC group (alln P<0.05).n Conclusion:High glucose can promote abnormal cell proliferation, increase mesangial matrix production and enhance oxidative stress response through upregulating SR-A expression, and ultimately aggravate cellular inflammatory damage in HMC, which may be associated with NLRP3-Caspase-1-IL-1β pathway regulated by SR-A expression.