半乳糖凝集素-3在蛛网膜下腔出血小鼠早期脑损伤中的作用与调节小胶质细胞极化相关

Role of galectin-3 in the early brain injury of mice with subarachnoid hemorrhage is associated with the regulation of microglia polarization

目的探讨半乳糖凝集素-3(galectin-3,Gal-3)对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后小胶质细胞极化的影响。方法使用C57BL/6雄性成年小鼠制作SAH或假手术模型,模型制作前48 h侧脑室注射Gal-3 siRNA或阴性对照siRNA。模型制作后24 h进行SAH评分和神经功能评分以及脑含水量和依文思蓝渗出量测定。应用蛋白质印迹分析检测小胶质细胞M1表型标志物[诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、CD11b、肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)]和M2表型标志物[CD206、YM1/2、精氨酸酶-1(arginase-1,Arg1)]表达。结果应用Gal-3 siRNA抑制Gal-3后,神经功能评分显著增加,SAH评分、脑含水量和伊文斯蓝渗出量显著降低(P均<0.001)。蛋白质印迹分析显示,抑制Gal-3后小胶质细胞M1表型标志物iNOS、CD11b和TNF-α表达显著降低,而M2表型标志物CD206、YM1/2和Arg1表达显著增高(P均<0.001)。结论抑制Gal-3表达能减轻SAH后早期脑损伤,其机制可能与调节小胶质细胞从M1表型向M2表型极化有关。

Objective To investigate the effect of galectin-3(gal-3)on microglia polarization after subarachnoid hemorrhage(SAH).Methods C57BL/6 male adult mice were used to induce SAH or sham operation models.Gal-3 siRNA or negative control siRNA was injected into the lateral ventricle 48 h before the model was induced.After 24 h of model preparation,the SAH score,neurological function score,brain water content,and Evans blue exudate were measured.Western blot analysis was used to detect the expressions of M1 phenotypic markers(inducible nitric oxide synthase[iNOS],CD11b,tumor necrosis factor[TNF]-α)and M2 phenotype markers(CD206,YM1/2,arginase-1[Arg1]).Results After using Gal-3 siRNA to inhibit Gal-3,the neurological function score significantly increased,while the SAH score,brain water content,and Evans blue exudate significantly decreased(P<0.001).Western blot analysis showed that the expressions of M1 phenotypic markers(iNOS,CD11b and TNF-α)in microglia were significantly decreased after Gal-3 inhibition,while the expressions of M2 phenotypic markers(CD206,YM1/2 and Arg1)were significantly increased(P<0.001).Conclusion Inhibition of Gal-3 expression can alleviate the early brain injury after SAH,and its mechanism may be associated with regulating the polarization of microglia from M1 to M2 phenotype.