机构:[1]Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command of Chinese PLA, Guangzhou 510010, Guangdong, China[2]Department of Anesthesiology, Second Affiliated Hospital, Guangzhou University of TCM, Guangzhou 510120, Guangdong, China
We constructed a water-soluble lipopolymer (WSLP) as a nonviral gene carrier to deliver siRNA targeting NR2B. The cytotoxicity and serum stability of WSLP loaded with siRNA were evaluated, and the knockdown efficiency of WSLP/NR2B-siRNA in PC12 cells was examined. The results showed that WSLP could protect the loading siRNAs from enzymatic degradation in serum and exhibit low cytotoxicity to cells. After transfection, WSLP/NR2B-siRNA complexes reduced the NR2B transcriptional level by 50% and protein level by 55% compared to control siRNA. Moreover, 3 days after intrathecal injection of WSLP/NR2B-siRNA complexes into rats, the NR2B protein expression decreased significantly to 58%, compared to control treatment (p < 0.01). Injection of WSLP with scrambled siRNA or of polyethylenimine (PEI) with NR2B-siRNA did not show this inhibitory effect. Additionally, injection of WSLP/NR2B-siRNA complexes significantly relieved inflammatory pain in rats at 3, 4, and 5 days with reduced MWT and decreased TWL scores, while injection of WSLP with scrambled siRNA or of PEI with NR2B-siRNA did not. These results demonstrated that WSLP can efficiently deliver siRNA targeting NR2B to PC12 cells and relieve pain in rats with chronic inflammatory pain.
基金:
National Natural
Science Foundation of China (nos. 81100817 and 81371233)
and Science and Technology Project of Guangdong Province
(no. 2014A020212554).
第一作者机构:[1]Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command of Chinese PLA, Guangzhou 510010, Guangdong, China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Peng Jie,Ma Jiahui,Yang Xue,et al.Water-Soluble Polymer Assists N-Methyl-D-Aspartic Acid Receptor 2B siRNA Delivery to Relieve Chronic Inflammatory Pain In Vitro and In Vivo[J].PAIN RESEARCH & MANAGEMENT.2018,2018:doi:10.1155/2018/7436060.
APA:
Peng, Jie,Ma, Jiahui,Yang, Xue,He, Huan,Wu, Haopeng...&Lu, Jianhua.(2018).Water-Soluble Polymer Assists N-Methyl-D-Aspartic Acid Receptor 2B siRNA Delivery to Relieve Chronic Inflammatory Pain In Vitro and In Vivo.PAIN RESEARCH & MANAGEMENT,2018,
MLA:
Peng, Jie,et al."Water-Soluble Polymer Assists N-Methyl-D-Aspartic Acid Receptor 2B siRNA Delivery to Relieve Chronic Inflammatory Pain In Vitro and In Vivo".PAIN RESEARCH & MANAGEMENT 2018.(2018)