CAJ | 학술논문

目的探讨脊髓背角小胶质细胞组织蛋白酶S(CatS)在大鼠骨癌痛维持中的作用.方法雌性未交配SD大鼠50只,4～6周龄,体重150～ 180 g,采用随机数字表法,将其分为5组(n=10):假手术组(S组)、骨癌痛组(BCP组)、假手术+CatS抑制剂吗啉亮氨酸高苯丙氨酸乙烯基苯基砜(LHVS)组(S+L组)、骨癌痛+二甲基亚砜组(BCP+D组)和骨癌痛+LHVS组(BCP+L组).左侧胫骨骨髓腔内接种浓度为2×107/ml Walker256细胞5μl制备大鼠骨癌痛模型.分别于造模后10、11、12d时S+L组和BCP+L组鞘内注射LHVS 50 nmol/10l,1次/d,BCP+D组给予等容量二甲基亚砜.分别于造模前1d(基础状态)及造模后3、6、9、10、11、12 d(T0-6)测定机械缩爪反应阈(MWT),分别于鞘内给药前、鞘内给药后0.5、1.0、3.0、6.0、9.0、12.0、24.0 h时测定(MWT).处死大鼠,取L4-6脊髓组织,采用免疫组化法测定OX-42表达.结果与S组比较,BCP组、BCP+D组和BCP+L组T2-6时MWT降低,脊髓背角OX-42表达上调(P＜0.01),S+L组MWT和脊髓背角OX-42表达差异无统计学意义(P＞0.05)；与BCP组比较,BCP+L组T4-6时MWT升高,脊髓背角OX-42表达下调(P＜0.01),BCP+D组MWT和脊髓背角0X-42表达差异无统计学意义(P＞0.05).S+L组和BCP+D组鞘内给药后3.0、6.0、9.0h时MWT低于BCP+D组(P＜0.01).结论脊髓背角小胶质细胞CatS激活参与了大鼠骨癌痛的维持.
목적 탐토척수배각소효질세포조직단백매S(CatS)재대서골암통유지중적작용.방법 자성미교배SD대서50지,4～6주령,체중150～ 180 g,채용수궤수자표법,장기분위5조(n=10):가수술조(S조)、골암통조(BCP조)、가수술+CatS억제제마람량안산고분병안산을희기분기풍(LHVS)조(S+L조)、골암통+이갑기아풍조(BCP+D조)화골암통+LHVS조(BCP+L조).좌측경골골수강내접충농도위2×107/ml Walker256세포5μl제비대서골암통모형.분별우조모후10、11、12d시S+L조화BCP+L조초내주사LHVS 50 nmol/10l,1차/d,BCP+D조급여등용량이갑기아풍.분별우조모전1d(기출상태)급조모후3、6、9、10、11、12 d(T0-6)측정궤계축조반응역(MWT),분별우초내급약전、초내급약후0.5、1.0、3.0、6.0、9.0、12.0、24.0 h시측정(MWT).처사대서,취L4-6척수조직,채용면역조화법측정OX-42표체.결과 여S조비교,BCP조、BCP+D조화BCP+L조T2-6시MWT강저,척수배각OX-42표체상조(P＜0.01),S+L조MWT화척수배각OX-42표체차이무통계학의의(P＞0.05)；여BCP조비교,BCP+L조T4-6시MWT승고,척수배각OX-42표체하조(P＜0.01),BCP+D조MWT화척수배각0X-42표체차이무통계학의의(P＞0.05).S+L조화BCP+D조초내급약후3.0、6.0、9.0h시MWT저우BCP+D조(P＜0.01).결론 척수배각소효질세포CatS격활삼여료대서골암통적유지.
Objective To investigate the role of cathepsin S (CatS) in spinal microglia in the maintenance of bone cancer pain (BCP) in rats.Methods Fifty unmated female Sprague-Dawley rats,aged 4-6 months,weighing 150-180 g,were randomly divided into 5 groups with 10 rats in each group:sham operation group (group S) ; group BCP; sham operation + CatS inhibitor morpholinurea-leucine-homophenylalanine-vinyl phenyl sulfone (LHVS) group (group S + L); BCP + dimethyl sulfoxide (DMSO) group (group BCP + D); BCP + LHVS group (group BCP + L).BCP was induced by inoculating 2 × 107/ml Walker256 mammary gland carcinoma cells 5 μl into the medullary cavity of the left tibia,while in S and S + L groups,Hank' s solution 5μl was injected into left tibia instead of Walker256 cells.At 10,11 and 12 days after inoculation,the rats in S + L and BCP + L groups received an intrathecal injection of LHVS 50 nmol/10μl,and the rats in group BCP + D received an intrathecal injection of 5 ％ DMSO 10 μl.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before inoculation (baseline) and 3,6,9,10,11 and 12 days after inoculation (T0-6).MWT was measured before intrathecal administration and at 0.5,1.0,3.0,6.0,9.0,12.0 and 24.0 h after intrathecal administration.The rats were sacrificed and the L4-6 segments of the spinal cord were removed for determination of the expression of OX-42 in the spinal dorsal horn by immunohistochemistry.Results Compared with group S,MWT was significantly decreased at T2-6 and the expression of OX-42 in spinal dorsal horn was up-regulated in BCP,BCP + D and BCP + L groups (P ＜ 0.01),and no significant changes in MWT and expression of OX-42 in spinal dorsal horn were found in S + L group (P ＞ 0.05).Compared with group BCP,MWT was significantly increased at T4-6 and the expression of OX-42 in spinal dorsal horn was down-regulated in group BCP+ L (P ＜ 0.01),and no significant change in MWT and the expression of OX-42 in spinal dorsal horn was found in group BCP + D (P ＞ 0.05).MWT was significantly decreased at 3.0,6.0 and 9.0 h after intrathecal administration in S + L and BCP + D groups as compared with BCP + D group (P ＜ 0.01).Conclusion Activation of CatS in spinal microglia is involved in the maintenance of BCP in rats.