摘要目的:探讨下调瞬时受体电位通道M2(TRPM2)表达对氯胺酮诱导的膀胱上皮细胞损伤的影响。方法:将TRPM2小干扰RNA(siRNA-TRPM2)及其阴性对照(siRNA-NC)转染至体外培养的人正常膀胱上皮细胞(SV-HUC-1)中，并用氯胺酮处理，记为si-TRPM2+氯胺酮组(si-TRPM2+Ketamine组)和si-NC+氯胺酮组(si-NC+Ketamine组)，另设氯胺酮组和对照组。采用qRT-PCR法检测SV-HUC-1细胞中的TRPM2表达，CCK-8法检测细胞增殖活性，流式细胞术检测细胞凋亡率，ELISA法检测细胞中的白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和氧化应激指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)等炎症因子水平，Western blot法检测相关蛋白的表达水平。结果:与对照组比较，氯胺酮组的SV-HUC-1细胞增殖活性、SOD、GSH-Px活性及Bcl-2蛋白表达均显著降低(均 P<0.05)，TRPM2的mRNA表达、TNF-α、IL-1β、IL-6水平、MDA含量和细胞凋亡率、Bax、Cleaved Caspase-3蛋白表达以及NLRP3、ASC、Caspase-1蛋白表达均显著升高(均 P<0.05)；si-NC+Ketamine组的上述指标与氯胺酮组比较，差异均无统计学意义(均 P>0.05)；与si-NC+Ketamine组比较，si-TRPM2+Ketamine组的SV-HUC-1细胞增殖活性、SOD、GSH-Px活性及Bcl-2蛋白表达均显著升高(均 P<0.05)，TRPM2的mRNA表达、TNF-α、IL-1β、IL-6水平、MDA含量和细胞凋亡率、Bax、Cleaved Caspase-3蛋白表达以及NLRP3、ASC、Caspase-1蛋白表达均显著降低(均 P<0.05)。 结论:下调TRPM2表达可抑制氯胺酮诱导的膀胱上皮细胞凋亡、炎症反应和氧化应激，进而减轻膀胱上皮细胞损伤，其可能是通过抑制NLRP3炎症小体激活发挥作用。

abstractsObjective:To investigate the effect of down-regulation the expression of transient receptor potential channel M2 (TRPM2) on ketamine induced bladder epithelial cell injury.Methods:TRPM2 small interfering RNA (siRNA-TRPM2) and its negative control (siRNA-NC) were transfected into human normal bladder epithelial cells (SV-HUC-1) cultured in vitro and treated with ketamine, which were recorded as si-TRPM2+ ketamine group (si-TRPM2+ ketamine group) and si-NC+ ketamine group (si-NC+ ketamine group), and ketamine group and control group were set up. The expression of TRPM2 in SV-HUC-1 cells was detected by qRT-PCR, the proliferation activity wasdetected by CCK-8, the apoptosis rate was detected by flow cytometry, and the levels of interleukin-6 (IL-6), interleukin-1β (IL-1 β), Tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were detected by ELISA, and the expression level of related proteins was detected by Western blot.Results:Compared with the control group, the proliferation activity, SOD, GSH-Px activity and Bcl-2 protein expression of SV-HUC-1 cells in ketamine group were significantly decreased(all P<0.05), and the expression of TRPM2 mRNA and TNF-α, IL-1 β, IL-6 level, MDA content and apoptosis rate, Bax, Cleared Caspase-3 protein expression, NLRP3, ASC and Caspase-1 protein expression were significantly increased (all P<0.05). Compared with ketamine group, there was no significant difference in the above indexes in si-NC+ ketamine group (all P>0.05). Compared with si-NC + ketamine group, the proliferation activity, SOD, GSH-Px activity and Bcl-2 protein expression of SV-HUC-1 cells in si-TRPM2+ ketamine group were significantly increased(all P<0.05), and the expression of TRPM2 mRNA and TNF-α, IL-1 β, IL-6 level, MDA content and apoptosis rate, Bax, Cleared Caspase-3 protein expression, NLRP3, ASC and Caspase-1 protein expression were significantly decreased (all P<0.05). Conclusions:Down-regulation of TRPM2 expression can inhibit ketamine induced apoptosis, inflammatory response and oxidative stress of bladder epithelial cells, and then reduce the damage of bladder epithelial cells, it may play a role by inhibiting the activation of NLRP3 inflammasome.