国际麻醉学与复苏杂志   2013, Issue (6): 2-2
    
单次鞘内注射mLin10-PDZ1结构域小肽抑制剂对骨癌痛小鼠痛行为学的影响
周瑜, 倪坤, 侯百灵, 马正良1()
1.徐州医学院
Effect of Single intrathecal injection the small peptide inhibitor of mLin10-PDZ1 domain on the behavior of bone cancer pain mouse
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摘要:

摘要:目的 探讨单次鞘内注射mLin10-PDZ1结构域小肽抑制剂对骨癌痛小鼠痛行为学的影响。方法 40只雄性C3H/HeJ小鼠随机分为肿瘤组(T组,n=32)和假手术对照组(S组,n=8)。将含有2×105个纤维肉瘤细胞NCTC2472的最小必需培养基(α-MEM)接种到T组小鼠右侧股骨远端骨髓腔,建立骨癌痛模型;S组小鼠骨髓腔注入不含有NCTC2472细胞的α-MEM。于接种前1d、接种后3d、5d、7d、10d、14d测定痛行为学指标:自发性抬足次数、机械痛缩足阈值(PWMT)。T组小鼠在接种后第14天,进一步分为对照control组(C组,n=8)和mLin10-PDZ1结构域小肽抑制剂2.5μg/5μl、5μg/5μl、10μg/5μl组(G1组, n=8,G2组,n=8,G3组,n=8)。G1~ G3组分别鞘内注射相应剂量的mLin10-PDZ1结构域小肽抑制剂,S组和C组鞘内注射等体积的溶媒10%DMSO。在给药后的2h、12h、24h分别测定各组小鼠的痛行为学指标。结果:与S组[(2.1±0.65)次]和术前基础值[(1.8±0.68)次]相比,肿瘤细胞接种后第14天T组小鼠自发性抬足次数[(13.46±1.44)次]显著增多( P<0.05),PWMT[(0.47±0.19)g]较S组[(1.70±0.31)g]和基础值[(1.83士0.23)g]降低(P<0.05)。 给药后2h,与C组及14d给药前比较,G1、G2和G3组自发性抬足次数减少,PWMT增高(P<0.05),且G3组较G1和G2组痛行为学改善更明显(P<0.05)。至12h,与C组相比,G2和G3组自发抬足次数减少(P<0.05),PWMT增高(P<0.05);而G1组给药后痛行为学无明显变化(P>0.05)。给药后24h,G3组与C组相比,自发抬足次数减少,PWMT升高,差异有统计学意义(P<0.05)。结论 鞘内单次注射mLin10-PDZ1结构域小肽抑制剂能够改善骨癌痛小鼠的痛行为。

关键词: mLin10-PDZ1结构域 ;小肽抑制剂;骨癌痛;小鼠
Abstract:

【Abstract】Objective To explore the effect of single intrathecal injection the small peptide inhibitor of mLin10-PDZ1 domain on the behavior of bone cancer pain mouse. Methods 40 male C3H/HeN mice were randomly divided into tumor group(group T,n=32) and sham group(group S,n=8). Osteosarcoma NCTC 2472 cells were inplanted into intramedullary space of right femurs of mice of group T to inducing ongoing bone cancerrelated pain behaviors. The sham group was inoculated by α-MEM without any cells. Pain ethology indexes such as the spontsneous lifting behaviors,the paw withdrawal mechanical threshold(PWMT) were observed on 1 d before inoculation and on 3d,5d,7d,10d,14d after inoculation to evaluate the mouse of bone cancer. On the 14th day after inoculation ,the mice of group T were further divided into control group(group C,n=8) and small peptide inhibitor of mLin10-PDZ1 domain 2.5μg/5μl、5μg/5μl、10μg/5μl (group G1, n = 8, group G2, n = 8, group G3, n = 8). Group G1~G3 were respectively treated by intrathecal injection of the corresponding dose of the small peptide inhibitor of mLin10-PDZ1 domain. Group S and group C were treated by intrathecal injection of the same volume of 10%DMSO. Pain ethology indexes mentioned above were observed at 2h,12h,24h after administration. Results (1)The significant increasing of spontaneous lifting behaviors(13.46 ± 1.44)]) ,the obvious decreasing of PWMT (1 .83 ± 0.23) g were observed on 14th d after inoculation in group T compared with group S and preoperative base level (P<0.05).(2) The spontaneous lifting behaviors were decreased,the PWMT was increased in groupG1,G2 and G3 compared with the base level on 14th d before and group C at 2h after administration(P<0.05). The analgesic effect of group G3 was more conspicuous than group G1 and G2(P<0.05). At 12h after administration, the spontaneous lifting behaviors were decreased,the PWMT was increased in groupG2 and G3 compared with group C(P<0.05). No obvious change of pain ethology indexes was observed in group G1(P>0.05). At 24h after administration,the spontaneous lifting was reduced and the PWMT was rised in group G3 compared with group C,the difference was statistically significant(P<0.05). Conclusion Intrathecal injection the small peptide inhibitor of mLin10-PDZ1 domain can efficiently improve the behaviors in the mouse model of bone cancer pain.

Key words: mLin10-PDZ1 domain;small peptide inhibitor;bone cancer pain;mouse