目的：探讨G蛋白偶联受体160（GPR160）信号通路对高糖环境下雪旺氏细胞（SCs）损伤的保护作用。方法：培养SCs细胞系RSC96，Control组使用DMEM培养基，150 mmol·L^-1葡萄糖（GLU）组将DMEM培养基中的GLU浓度换为150 mmol·L^-1。小干扰RNA-GPR160敲降质粒组（siGPR160）和阴性对照组（siNC）分别转染150 mmol·L^-1 GLU组的RSC96细胞。四甲基偶氮唑蓝（MTT）法检测细胞活力；流式细胞术分析细胞中Ca²⁺水平和凋亡率变化；透射电子显微镜观察内质网（ER）超微结构；蛋白质印迹法和（或）实时荧光定量PCR （qRT-PCR）法检测细胞中GPR160/可卡因和安非他明调节的转录肽（CARTp）信号通路的表达、C/EBP-同源蛋白（CHOP）相关的生长阻滞以及DNA损伤诱导蛋白34（GADD34）、ER氧化还原酶1α（Ero1α）、CHOP上游的蛋白需肌醇酶1（IRE1α）和X-框结合蛋白1（XBP-1）的表达。结果：与Control组比较，150 mmol·L^-1的GLU抑制RSC96细胞活力，诱导细胞凋亡率和Ca²⁺水平增加（均P<0.05），促进细胞中ER出现碎片形态，150 mmol·L^-1的GLU还增加GPR160、CARTp、GADD34、Ero1α、IRE1α、XBP-1的表达量（均P<0.05）；用siGPR160敲降GPR160后，不仅下调CARTp、GADD34、Ero1α、IRE1α、XBP-1的表达量（均P<0.05），还上调RSC96细胞活力（P<0.05），降低了细胞凋亡率和Ca²⁺水平（均P<0.05），并使细胞中ER形态趋于完整。结论：敲降GPR160蛋白能通过抑制GPR160信号通路改善高糖环境下SCs凋亡和ER应激损伤。

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