中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2013年
8期
920-923
,共4页
孙艳%胡计嬅%王加玉%杨建平
孫豔%鬍計嬅%王加玉%楊建平
손염%호계화%왕가옥%양건평
丝裂原激活蛋白激酶类%受体,趋化因子%骨肿瘤%疼痛%脊髓
絲裂原激活蛋白激酶類%受體,趨化因子%骨腫瘤%疼痛%脊髓
사렬원격활단백격매류%수체,추화인자%골종류%동통%척수
Mitogen-activated protein kinases%Receptors,chemokine%Bone neoplasms%Pain%Spinal cord
目的 评价骨癌痛大鼠脊髓背角丝裂原活化蛋白激酶激酶/细胞外信号调节激酶(MEK/ERK)信号转导通路与CX3C趋化因子受体1(CX3CR1)的关系.方法 雌性未交配SD大鼠50只,体重150～ 180 g,采用随机数字表法分为5组(n=10):假手术组(Ⅰ组)、骨癌痛组(Ⅱ组)、假手术+ MEK抑制剂U0126组(Ⅲ组)、骨癌痛组+5％二甲基亚砜(DMSO)组(Ⅳ组)和骨癌痛+MEK抑制剂U0126组(Ⅴ组).左侧胫骨骨髓腔内接种Walker 256乳腺癌肿瘤细胞制备大鼠骨癌痛模型.Ⅲ组和Ⅴ组于接种后第10 ～ 12天鞘内注射U0126 10 μg/10 μl,1次/d,Ⅳ组鞘内注射等体积5％DMSO,于接种前及接种后第3、6、9、10天和第11、12天给药后测定机械痛阈.接种后第12天给药后处死大鼠,取L4-6脊髓背角,分别采用免疫组化法和Western blot法检测CX3CR1的表达.结果 与Ⅰ组和Ⅲ组比较,Ⅱ组、Ⅳ组和Ⅴ组大鼠接种后第6～ 12天机械痛阈降低,脊髓背角CX3CR1表达上调(P＜0.01)；与Ⅱ组和Ⅳ组比较,Ⅴ组接种后第10 ～ 12天机械痛阈升高,脊髓背角CX3CR1表达下调(P＜0.01).结论 脊髓背角MEK/ERK信号转导通路可能通过调节CX3CR1表达参与大鼠骨癌痛的发生和发展.
目的 評價骨癌痛大鼠脊髓揹角絲裂原活化蛋白激酶激酶/細胞外信號調節激酶(MEK/ERK)信號轉導通路與CX3C趨化因子受體1(CX3CR1)的關繫.方法 雌性未交配SD大鼠50隻,體重150～ 180 g,採用隨機數字錶法分為5組(n=10):假手術組(Ⅰ組)、骨癌痛組(Ⅱ組)、假手術+ MEK抑製劑U0126組(Ⅲ組)、骨癌痛組+5％二甲基亞砜(DMSO)組(Ⅳ組)和骨癌痛+MEK抑製劑U0126組(Ⅴ組).左側脛骨骨髓腔內接種Walker 256乳腺癌腫瘤細胞製備大鼠骨癌痛模型.Ⅲ組和Ⅴ組于接種後第10 ～ 12天鞘內註射U0126 10 μg/10 μl,1次/d,Ⅳ組鞘內註射等體積5％DMSO,于接種前及接種後第3、6、9、10天和第11、12天給藥後測定機械痛閾.接種後第12天給藥後處死大鼠,取L4-6脊髓揹角,分彆採用免疫組化法和Western blot法檢測CX3CR1的錶達.結果 與Ⅰ組和Ⅲ組比較,Ⅱ組、Ⅳ組和Ⅴ組大鼠接種後第6～ 12天機械痛閾降低,脊髓揹角CX3CR1錶達上調(P＜0.01)；與Ⅱ組和Ⅳ組比較,Ⅴ組接種後第10 ～ 12天機械痛閾升高,脊髓揹角CX3CR1錶達下調(P＜0.01).結論 脊髓揹角MEK/ERK信號轉導通路可能通過調節CX3CR1錶達參與大鼠骨癌痛的髮生和髮展.
목적 평개골암통대서척수배각사렬원활화단백격매격매/세포외신호조절격매(MEK/ERK)신호전도통로여CX3C추화인자수체1(CX3CR1)적관계.방법 자성미교배SD대서50지,체중150～ 180 g,채용수궤수자표법분위5조(n=10):가수술조(Ⅰ조)、골암통조(Ⅱ조)、가수술+ MEK억제제U0126조(Ⅲ조)、골암통조+5％이갑기아풍(DMSO)조(Ⅳ조)화골암통+MEK억제제U0126조(Ⅴ조).좌측경골골수강내접충Walker 256유선암종류세포제비대서골암통모형.Ⅲ조화Ⅴ조우접충후제10 ～ 12천초내주사U0126 10 μg/10 μl,1차/d,Ⅳ조초내주사등체적5％DMSO,우접충전급접충후제3、6、9、10천화제11、12천급약후측정궤계통역.접충후제12천급약후처사대서,취L4-6척수배각,분별채용면역조화법화Western blot법검측CX3CR1적표체.결과 여Ⅰ조화Ⅲ조비교,Ⅱ조、Ⅳ조화Ⅴ조대서접충후제6～ 12천궤계통역강저,척수배각CX3CR1표체상조(P＜0.01)；여Ⅱ조화Ⅳ조비교,Ⅴ조접충후제10 ～ 12천궤계통역승고,척수배각CX3CR1표체하조(P＜0.01).결론 척수배각MEK/ERK신호전도통로가능통과조절CX3CR1표체삼여대서골암통적발생화발전.
Objective To evaluate the relationship between MEK/extracellular signal-regulated kinase (ERK) signal transduction pathway and CX3CR1 in the spinal dorsal horns in a rat model of bone cancer pain (BCP).Methods Fifty female Sprague-Dawley rats,weighing 150-180 g,were randomly divided into 5 groups (n =10 each):sham operation group (group Ⅰ),BCP group (group Ⅱ),sham operation + U0126 group (group Ⅲ),BCP+ 5％ dimethyl sulfoxide (DMSO) group (group Ⅳ),BCP + U0126 (MEK inhibitor) group (group Ⅴ).BCP was induced by inoculating Walker 256 mammary gland carcinoma cells into the medullary cavity of the left tibia.In Ⅲ and Ⅴ groups,U0126 10 μg/10 μl was injected intrathecally once a day starting from day 10 after inoculation to day 12 after inoculation,while the equal volume of 5％ DMSO was injected in group Ⅳ.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before inoculation (baseline),3,6,9,and 10 days after inoculation,and after administration on 11 and 12 days after inoculation.The rats were sacrificed after administration on day 12 after inoculation and the L4.6 segments of the spinal cord were removed for determination of CX3CR1 expression in spinal dorsal horns (by Western blot and immunohistochemistry).Results Compared with Ⅰ and Ⅲ groups,MWT was significantly decreased at 6-12 days after inoculation,and the expression of CX3CR1 in spinal dorsal horns was up-regulated in Ⅱ,Ⅳ and Ⅴ groups (P ＜0.01).Compared with Ⅱ and Ⅳ groups,MWT was significantly increased at 10-12 days after inoculation,and the expression of CX3CR1 in spinal dorsal horns was down-regulated (P ＜ 0.01).Conclusion MEK/ERK signal transduction pathway in the spinal dorsal horns is involved in the development and maintenance of BCP in rats possibly through regulating the expression of CX3CR1.
