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[目的]探讨miR-138-5p在氯化锰(MnCl2)诱导人神经母细胞瘤SH-SY5Y细胞自噬中的作用及其机制.[方法]以生理盐水处理组作为对照,0.125、0.25、0.5、1 mmol/L MnCl2染毒SH-SY5Y细胞6h后,利用MTT法检测细胞活力;0.25和0.5 mmol/LMnCl2处理细胞6h后,采用Western blot检测自噬相关蛋白LC3和Beclin1的表达;MnCl2染毒6h后,使用反转录PCR和Western blot检测miR-138-5p和组蛋白脱乙酰酶SIRT1 mRNA以及蛋白表达的变化;使用miRNA模拟物转染细胞实现miR-138-5p过表达,然后0.25 mmol/L MnCl2染毒6h,检测SIRT1 mRNA和蛋白的表达以及自噬相关蛋白LC3和Beclin1的变化.[结果] MnCl2可剂量依赖性地降低SH-SY5Y细胞活力(趋势x2=12.42,P＜0.05).与对照组相比,0.25、0.5 mmol/LMnCl2染毒后,自噬相关蛋白LC3-Ⅱ/LC3-Ⅰ值和Beclin1表达水平明显增加(P＜0.05);miR-138-5p表达下调,SIRT1 mRNA及蛋白表达上调(均P＜0.05).miR-138-5p过表达后,相比未过表达的MnCl2染毒组,SIRT1 mRNA及蛋白表达均出现下调,自噬相关蛋白LC3-Ⅱ/LC3-Ⅰ值及Beclin1蛋白表达也相应下调(P＜0.05).[结论] miR-138-5p过表达可通过调节SIRT1的表达抑制锰诱导的SH-SY5Y细胞自噬.“,”[Objective] To investigate the role and mechanism of miR-138-5p in autophagy induced by manganese chloride (MnCl2) in human neuroblastoma SH-SY5Y cells.[Methods] SH-SY5Y cells were treated with 0.125,0.25,0.5,and 1 mmol/L MnCl2,respectively.Control cells were treated with normal saline.After 6 h of the treatmem,MTF test was used to detect the cell viability of SH-SY5Y cells.After 6 h of the treatment,Western blot was used to detect the expression of autophagy related proteins LC3 and Beclin1,reverse transcription PCR (RT-PCR) and western blot were used to detect the expression of miR-138-5p and the mRNA and protein expressions of histone deacetylase SIRT1.Then the cells were transfected by miRNA mimics to induce overexpressed miR-138-5p,and treated with 0.25 mmol/L MnCl2 for 6h to detect the expressions of SIRT1 at mRNA and protein levels and the expressions of autophagy related proteins LC3 and Beclin1.[Results] MnCl2 dose-dependently suppressed the viability of SH-SY5Y cells (trend x2=12.42,P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio and Beclin1 expression level were significantly elevated in the 0.25 and 0.5 mmol/L MnCl2-treated cells compared with the controls (P＜ 0.05).MnCl2 down-regulated the expression of miR-138-5p,and up-regulated the mRNA and protein expressions of SIRT1 (P＜0.05).Furthermore,the cells with overexpressed miR-138-5p showed decreased expression of SIRT1 both at mRNA and protein levels and decreased expressions of LC3-Ⅱ/LC3-Ⅰ and Beclin1 protein (P＜ 0.05).[Conclusion] Overexpression of miR-138-5p suppresses manganese-induced autophagy by modulating the expression of SIRT1.