目的研究脊髓Sirt1在大鼠化疗后神经病理性痛中的作用。方法造模分组:将健康成年雄性s-D大鼠18只随机分为3组:紫杉醇组(P组)、溶媒组(V组)、正常组(N组),每组6只。检测(-1、5、7、14天)各组大鼠机械缩足反射阈值(MWT)及脊髓中Sirt1、核因子-κB(NF-κB)和肿瘤坏死因子-α(TNF-α)mR-NA的含量。治疗分组:健康成年雄性s-D大鼠30只随机分为5组:紫杉醇组(P组)、紫杉醇+DMSO组(P+D组)、紫杉醇+白藜芦醇组(P+R组)、溶媒+DMSO组(V+D组)、溶媒+白藜芦醇组(V+R组),每组6只。测定各组大鼠(-1、7、8、9、10天)MWT,并在第10天检测各组大鼠脊髓中Sirt1、NF-κB和TNF-αmRNA的含量。结果与造模前1天相比,造模后5、7和14天紫杉醇组大鼠MWT明显降低。脊髓中Sirt1mRNA含量降低(P〈0.05)、NF-κB和TNF-α mRNA的含量增加(P〈0.01)。与紫杉醇+DMSO组相比,第7、8、9、10天紫杉醇+白藜芦醇组大鼠的MWT明显增加。第10天脊髓中Sirt1mRNA含量明显增加(P〈0.05),NF-κB和TNF-αmRNA的含量变化无统计学差异(P〉0.05)。结论激动脊髓中Sirt1信号可以减轻大鼠化疗药物引起的神经病理性痛。
Objective To investigate the effects of siauin 1 ( Sirt1 ) on the neuropathic pain induced by paclitaxel. Methods A rat model of paelitaxel - induced pain was established through intraperitoneal injection of 2 mg/kg paclitaxel on Days 0, 2, 4 and 6. A total of 18 rats were randomly divided into the following groups (n = 6) : a paclitaxel group (P) , a vehicle group (V) , and a naive group (N). The mechanical withdrawal threshold (MWT) was evaluated. The levels of spinal nuclear factor - κB ( NF - κB ), spinal Sial and tumor necrosis factor - α ( TNF - α ) mRNA were measured on the day before modeling and on Days 5,7 and 14. For treatment, another 30 rats were randomly divided into five groups ( n = 6 ) : a paclitaxel group (P) , a paclitaxel + DMSO group ( P + D), a paclitaxel + Res group ( P + R), a vehicle + DMSO group (V + D) , and a vehicle + Res group (V + R). The MWT of rats were evaluated on the day before modeling and on Days 7, 8, 9 and 10, while the levels of spinal Sirt1, NF - κB and TNF -α mRNA were meas- ured on Day 10. Results The paclitaxel group presented remarkable decreases in MWT and Sial mRNA ( P 〈 0.05 ) but significant increases in the levels of spinal NF - κB and TNF -α mRNA on Days 5, 7 and 14 (P 〈0.01 ) , compared with those on the day before modeling. The Paclitaxel + Res group produced obvious increases in MWT on Days 7, 8, 9 and 10 and Sial mRNA on Day 10, compared with the Paclitaxel + DMSO group (P 〈 0.05). However, no statistical difference was found as to the levels of NF - κB and TNF - α mRNA ( P 〉 0. 05 ). Conclusions Activation of spinal Sial can attenuate the neuropathic pain induced by paclitaxel in rats.