脊髓小胶质细胞在SD大鼠骨癌痛中的变化

目的 观察SD大鼠一侧胫骨注射同系Walker 256癌细胞后脊髓小胶质细胞的变化.方法 腹水传代Walker 256癌细胞种植于大鼠一侧胫骨建立骨癌痛模型,25只雌性SD大鼠,体质量150～180 g,随机均分为5组:对照组(N)、热杀死肿瘤细胞组(K)、骨癌痛早期组(C1,种植后第6天)、骨癌痛中期组(C2,种植后第12天)、骨癌痛晚期组(C3,种植后第18天).结果 骨癌痛大鼠在出现自发痛行为与机械性痛觉过敏的同时,两侧脊髓L4～L6 OX-42免疫组织化学染色显著增强,细胞明显增大,染色加深,与N组及K组比较,差异均有统计学意义(P<0.05,P<0.01);OX-42染色增强以C1组最为显著,术后第6～18天逐步降低,C1组与C2或C3组比较,差异均有统计学意义(P<0.05,P<0.01).结论 胫骨注射Walker 256癌细胞后激活脊髓小胶质细胞;小胶质细胞在两侧脊髓灰质后角均有激活,反映了本模型骨癌痛特征中"镜像痛"的产生机制;小胶质细胞在骨癌痛早期激活最为明显.     

脊髓小胶质细胞在SD大鼠骨癌痛中的变化

目的 观察SD大鼠一侧胫骨注射同系Walker 256癌细胞后脊髓小胶质细胞的变化.方法 腹水传代Walker 256癌细胞种植于大鼠一侧胫骨建立骨癌痛模型,25只雌性SD大鼠,体质量150～180 g,随机均分为5组:对照组(N)、热杀死肿瘤细胞组(K)、骨癌痛早期组(C1,种植后第6天)、骨癌痛中期组(C2,种植后第12天)、骨癌痛晚期组(C3,种植后第18天).结果 骨癌痛大鼠在出现自发痛行为与机械性痛觉过敏的同时,两侧脊髓L4～L6 OX-42免疫组织化学染色显著增强,细胞明显增大,染色加深,与N组及K组比较,差异均有统计学意义(P<0.05,P<0.01);OX-42染色增强以C1组最为显著,术后第6～18天逐步降低,C1组与C2或C3组比较,差异均有统计学意义(P<0.05,P<0.01).结论 胫骨注射Walker 256癌细胞后激活脊髓小胶质细胞;小胶质细胞在两侧脊髓灰质后角均有激活,反映了本模型骨癌痛特征中"镜像痛"的产生机制;小胶质细胞在骨癌痛早期激活最为明显.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

目的 评价脊髓胶质细胞在小鼠骨癌痛形成中的作用.方法 健康雄性C3H/He小鼠40只,周龄8～10周,体重18～22 g,随机分为4组(n=10):假手术组(S组)、骨癌痛组(B组)、PBS组(P组)和米诺环素组(M组).S组跟骨骨髓腔内注射PBS 10 μl;余3组跟骨骨髓腔内注射含2×105个骨纤维肉瘤细胞的PBS 10 μl制备骨癌痛模型,于造模前即刻开始PBS组鞘内注射PBS 5μl,M组鞘内注射米诺环素(用PBS溶解为0.2 mmol/L)5μl,1次/d,连续11 d.于造模前1 d、造模后即刻、3、5、7、9、11 d时测定机械痛阈;于造模后3、7、9、11 d机械痛阈测定结束后测定冷痛阈.痛阈测定结束后处死小鼠,取脊髓组织,测定神经胶质纤维酸性蛋白(GFAP)和CD11b的表达水平.结果 与S组比较,B组和P组造模后3-11 d时、M组造模后3、5 d时机械痛阈升高,B组、P组和M组造模后7～11 d时冷痛阈升高,脊髓CD11b和GFAP表达上调(P<0.05).与B组比较,M组造模后3-11 d时机械痛阈降低,造模后7-11 d时冷痛阈降低,脊髓CD11b和GFAP表达下调(P<0.05).结论 脊髓胶质细胞(星形胶质细胞和小胶质细胞)的激活参与了小鼠骨癌痛的形成.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

Objective To evaluate the role of gliocyte in the spinal cord in the development of bone cancer pain (BCP) in mice. Methods Forty male C3H/He mice aged 8-10 weeks weighing 18-22 g were randomly divided into 4 groups ( n = 10 each) : group I sham operation (group S) , group II BCP, group Ⅲ PBS and group IV minocyline (group M) . In group BCP, PBS and M, bone cancer pain was produced by injection of NCTC2472 fibrosarcoma cell suspension (2 x 105 cells) 10 μl into medullary cavity of calcaneus bone, while in group S, PBS solution 10 μl was injected instead of cancer cell suspension. In group PBS and M, PBS 5 μl and minocyline 5 μl (dissolved to 0.2 mmol/L in PBS)_were given IT immediately before cancer cell inoculation once a day for 11 consecutive days respectively. Mechanical pain threshold was measured at 1 d before cancer cell inoculation, and at 0, 3, 5, 7, 9 and 11d after cancer cell inoculation. Cold pain threshold was measured at 3, 7, 9 and 11d after cancer cell inoculation. The animals were killed after measurement of pain threshold and L4-6, segment of spinal cord was removed for determination of GFAP and CD11b expression by Western blot. Results Compared with group S, mechanical pain threshold was significantly increased at 3-11 d after cancer cell inoculation in group BCP and PBS, and at 3 and S d after cancer cell inoculation in group M, and cold pain threshold was significantly increased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was up-regulated in group BCP, PBS and M ( P < 0.05) . Compared with group BCP, mechanical pain threshold was significantly decreased at 3-11 d after cancer cell inoculation, cold pain threshold was significantly decreased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was down-regulated in group M ( P <0.05) . ConclusionThe activiton of gliocyte in the spinal cord is involved in the development of bone cancer pian in mice.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

Objective To evaluate the role of gliocyte in the spinal cord in the development of bone cancer pain (BCP) in mice. Methods Forty male C3H/He mice aged 8-10 weeks weighing 18-22 g were randomly divided into 4 groups ( n = 10 each) : group I sham operation (group S) , group II BCP, group Ⅲ PBS and group IV minocyline (group M) . In group BCP, PBS and M, bone cancer pain was produced by injection of NCTC2472 fibrosarcoma cell suspension (2 x 105 cells) 10 μl into medullary cavity of calcaneus bone, while in group S, PBS solution 10 μl was injected instead of cancer cell suspension. In group PBS and M, PBS 5 μl and minocyline 5 μl (dissolved to 0.2 mmol/L in PBS)_were given IT immediately before cancer cell inoculation once a day for 11 consecutive days respectively. Mechanical pain threshold was measured at 1 d before cancer cell inoculation, and at 0, 3, 5, 7, 9 and 11d after cancer cell inoculation. Cold pain threshold was measured at 3, 7, 9 and 11d after cancer cell inoculation. The animals were killed after measurement of pain threshold and L4-6, segment of spinal cord was removed for determination of GFAP and CD11b expression by Western blot. Results Compared with group S, mechanical pain threshold was significantly increased at 3-11 d after cancer cell inoculation in group BCP and PBS, and at 3 and S d after cancer cell inoculation in group M, and cold pain threshold was significantly increased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was up-regulated in group BCP, PBS and M ( P < 0.05) . Compared with group BCP, mechanical pain threshold was significantly decreased at 3-11 d after cancer cell inoculation, cold pain threshold was significantly decreased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was down-regulated in group M ( P <0.05) . ConclusionThe activiton of gliocyte in the spinal cord is involved in the development of bone cancer pian in mice.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

Objective To evaluate the role of gliocyte in the spinal cord in the development of bone cancer pain (BCP) in mice. Methods Forty male C3H/He mice aged 8-10 weeks weighing 18-22 g were randomly divided into 4 groups ( n = 10 each) : group I sham operation (group S) , group II BCP, group Ⅲ PBS and group IV minocyline (group M) . In group BCP, PBS and M, bone cancer pain was produced by injection of NCTC2472 fibrosarcoma cell suspension (2 x 105 cells) 10 μl into medullary cavity of calcaneus bone, while in group S, PBS solution 10 μl was injected instead of cancer cell suspension. In group PBS and M, PBS 5 μl and minocyline 5 μl (dissolved to 0.2 mmol/L in PBS)_were given IT immediately before cancer cell inoculation once a day for 11 consecutive days respectively. Mechanical pain threshold was measured at 1 d before cancer cell inoculation, and at 0, 3, 5, 7, 9 and 11d after cancer cell inoculation. Cold pain threshold was measured at 3, 7, 9 and 11d after cancer cell inoculation. The animals were killed after measurement of pain threshold and L4-6, segment of spinal cord was removed for determination of GFAP and CD11b expression by Western blot. Results Compared with group S, mechanical pain threshold was significantly increased at 3-11 d after cancer cell inoculation in group BCP and PBS, and at 3 and S d after cancer cell inoculation in group M, and cold pain threshold was significantly increased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was up-regulated in group BCP, PBS and M ( P < 0.05) . Compared with group BCP, mechanical pain threshold was significantly decreased at 3-11 d after cancer cell inoculation, cold pain threshold was significantly decreased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was down-regulated in group M ( P <0.05) . ConclusionThe activiton of gliocyte in the spinal cord is involved in the development of bone cancer pian in mice.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

Objective To evaluate the role of gliocyte in the spinal cord in the development of bone cancer pain (BCP) in mice. Methods Forty male C3H/He mice aged 8-10 weeks weighing 18-22 g were randomly divided into 4 groups ( n = 10 each) : group I sham operation (group S) , group II BCP, group Ⅲ PBS and group IV minocyline (group M) . In group BCP, PBS and M, bone cancer pain was produced by injection of NCTC2472 fibrosarcoma cell suspension (2 x 105 cells) 10 μl into medullary cavity of calcaneus bone, while in group S, PBS solution 10 μl was injected instead of cancer cell suspension. In group PBS and M, PBS 5 μl and minocyline 5 μl (dissolved to 0.2 mmol/L in PBS)_were given IT immediately before cancer cell inoculation once a day for 11 consecutive days respectively. Mechanical pain threshold was measured at 1 d before cancer cell inoculation, and at 0, 3, 5, 7, 9 and 11d after cancer cell inoculation. Cold pain threshold was measured at 3, 7, 9 and 11d after cancer cell inoculation. The animals were killed after measurement of pain threshold and L4-6, segment of spinal cord was removed for determination of GFAP and CD11b expression by Western blot. Results Compared with group S, mechanical pain threshold was significantly increased at 3-11 d after cancer cell inoculation in group BCP and PBS, and at 3 and S d after cancer cell inoculation in group M, and cold pain threshold was significantly increased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was up-regulated in group BCP, PBS and M ( P < 0.05) . Compared with group BCP, mechanical pain threshold was significantly decreased at 3-11 d after cancer cell inoculation, cold pain threshold was significantly decreased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was down-regulated in group M ( P <0.05) . ConclusionThe activiton of gliocyte in the spinal cord is involved in the development of bone cancer pian in mice.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

Objective To evaluate the role of gliocyte in the spinal cord in the development of bone cancer pain (BCP) in mice. Methods Forty male C3H/He mice aged 8-10 weeks weighing 18-22 g were randomly divided into 4 groups ( n = 10 each) : group I sham operation (group S) , group II BCP, group Ⅲ PBS and group IV minocyline (group M) . In group BCP, PBS and M, bone cancer pain was produced by injection of NCTC2472 fibrosarcoma cell suspension (2 x 105 cells) 10 μl into medullary cavity of calcaneus bone, while in group S, PBS solution 10 μl was injected instead of cancer cell suspension. In group PBS and M, PBS 5 μl and minocyline 5 μl (dissolved to 0.2 mmol/L in PBS)_were given IT immediately before cancer cell inoculation once a day for 11 consecutive days respectively. Mechanical pain threshold was measured at 1 d before cancer cell inoculation, and at 0, 3, 5, 7, 9 and 11d after cancer cell inoculation. Cold pain threshold was measured at 3, 7, 9 and 11d after cancer cell inoculation. The animals were killed after measurement of pain threshold and L4-6, segment of spinal cord was removed for determination of GFAP and CD11b expression by Western blot. Results Compared with group S, mechanical pain threshold was significantly increased at 3-11 d after cancer cell inoculation in group BCP and PBS, and at 3 and S d after cancer cell inoculation in group M, and cold pain threshold was significantly increased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was up-regulated in group BCP, PBS and M ( P < 0.05) . Compared with group BCP, mechanical pain threshold was significantly decreased at 3-11 d after cancer cell inoculation, cold pain threshold was significantly decreased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was down-regulated in group M ( P <0.05) . ConclusionThe activiton of gliocyte in the spinal cord is involved in the development of bone cancer pian in mice.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

Objective To evaluate the role of gliocyte in the spinal cord in the development of bone cancer pain (BCP) in mice. Methods Forty male C3H/He mice aged 8-10 weeks weighing 18-22 g were randomly divided into 4 groups ( n = 10 each) : group I sham operation (group S) , group II BCP, group Ⅲ PBS and group IV minocyline (group M) . In group BCP, PBS and M, bone cancer pain was produced by injection of NCTC2472 fibrosarcoma cell suspension (2 x 105 cells) 10 μl into medullary cavity of calcaneus bone, while in group S, PBS solution 10 μl was injected instead of cancer cell suspension. In group PBS and M, PBS 5 μl and minocyline 5 μl (dissolved to 0.2 mmol/L in PBS)_were given IT immediately before cancer cell inoculation once a day for 11 consecutive days respectively. Mechanical pain threshold was measured at 1 d before cancer cell inoculation, and at 0, 3, 5, 7, 9 and 11d after cancer cell inoculation. Cold pain threshold was measured at 3, 7, 9 and 11d after cancer cell inoculation. The animals were killed after measurement of pain threshold and L4-6, segment of spinal cord was removed for determination of GFAP and CD11b expression by Western blot. Results Compared with group S, mechanical pain threshold was significantly increased at 3-11 d after cancer cell inoculation in group BCP and PBS, and at 3 and S d after cancer cell inoculation in group M, and cold pain threshold was significantly increased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was up-regulated in group BCP, PBS and M ( P < 0.05) . Compared with group BCP, mechanical pain threshold was significantly decreased at 3-11 d after cancer cell inoculation, cold pain threshold was significantly decreased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was down-regulated in group M ( P <0.05) . ConclusionThe activiton of gliocyte in the spinal cord is involved in the development of bone cancer pian in mice.     

脊髓胶质细胞在小鼠骨癌痛形成中的作用

Objective To evaluate the role of gliocyte in the spinal cord in the development of bone cancer pain (BCP) in mice. Methods Forty male C3H/He mice aged 8-10 weeks weighing 18-22 g were randomly divided into 4 groups ( n = 10 each) : group I sham operation (group S) , group II BCP, group Ⅲ PBS and group IV minocyline (group M) . In group BCP, PBS and M, bone cancer pain was produced by injection of NCTC2472 fibrosarcoma cell suspension (2 x 105 cells) 10 μl into medullary cavity of calcaneus bone, while in group S, PBS solution 10 μl was injected instead of cancer cell suspension. In group PBS and M, PBS 5 μl and minocyline 5 μl (dissolved to 0.2 mmol/L in PBS)_were given IT immediately before cancer cell inoculation once a day for 11 consecutive days respectively. Mechanical pain threshold was measured at 1 d before cancer cell inoculation, and at 0, 3, 5, 7, 9 and 11d after cancer cell inoculation. Cold pain threshold was measured at 3, 7, 9 and 11d after cancer cell inoculation. The animals were killed after measurement of pain threshold and L4-6, segment of spinal cord was removed for determination of GFAP and CD11b expression by Western blot. Results Compared with group S, mechanical pain threshold was significantly increased at 3-11 d after cancer cell inoculation in group BCP and PBS, and at 3 and S d after cancer cell inoculation in group M, and cold pain threshold was significantly increased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was up-regulated in group BCP, PBS and M ( P < 0.05) . Compared with group BCP, mechanical pain threshold was significantly decreased at 3-11 d after cancer cell inoculation, cold pain threshold was significantly decreased at 7-11 d after cancer cell inoculation, and expression of CD11b and GFAP was down-regulated in group M ( P <0.05) . ConclusionThe activiton of gliocyte in the spinal cord is involved in the development of bone cancer pian in mice.     

脊髓背角小胶质细胞组织蛋白酶S在大鼠骨癌痛维持中的作用

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.     

糖尿病大鼠痛性周围神经病变时脊髓小胶质细胞的活化

目的 评价糖尿病大鼠痛性周围神经病变时脊髓小胶质细胞的活化.方法 SD大鼠25只,2月龄,雌雄不限,腹腔注射1%链脲佐菌素60 mg/kg以制备大鼠糖尿病痛性周围神经病变模型,取造模成功的10只SD大鼠作为糖尿病痛性周围神经病变组(DM组),另取10只同月龄SD大鼠作为对照组(NC组).分别于注射前(T1)、注射后2、7、14、21、28 d(T2～6)时称量体重,取尾静脉血0.1 ml测定血糖水平,于T1、T3～6时测定大鼠右后爪机械缩足反应阈值;注射28 d时麻醉大鼠,取L4.5脊髓制备切片,采用免疫组化法检测脊髓小胶质细胞补体受体3(CR3)的表达.结果 与NC组比较,DM组T2～6时血糖升高、体重下降,T4～6时机械缩足反应阈值降低,T6时小胶质细胞CR3表达上调(P<0.05或0.01);与T1时比较,DM组T2～6时血糖升高、体重下降,T6时机械缩足反应阈值降低(P<0.01).结论 脊髓小胶质细胞的活化与大鼠糖尿病痛性周围神经病变的发病有关.     

大鼠乳腺癌细胞移植复制胫骨癌痛模型

目的探讨大鼠乳腺癌细胞系制作胫骨癌痛模型。方法选择雌性SD大鼠12只,左侧胫骨上段骨髓腔注入3μl MADB-106大鼠乳腺癌细胞(4.8×10~9个/L)。术前及术后22d,隔日大鼠观察机械痛及辐射热痛阈值变化。于术后8、14、22d,将大鼠麻醉后术侧后肢进行X射线摄片和苏木素-伊红(HE)染色观察术后骨质破坏情况。结果12只大鼠术后14～22d比术后的前12d缩爪阈值和辐射热痛相比差异有统计学意义(P＜0.05)；术后22d放射学显示严重的骨破坏,多处骨皮质缺失；术后14d可见肿瘤细胞充填骨髓腔,引起骨小梁广泛破坏；术后22d可见肿瘤细胞穿破骨皮质,侵及周围肌肉及软组织。结论采用MADB-106乳腺癌细胞系制作大鼠胫骨癌痛模型是可取的。     

神经病理性疼痛中脊髓小胶质细胞活化的分子机制

背景 研究表明脊髓小胶质细胞活化对神经元功能调控起重要作用,并可影响脊髓背角伤害性信号的传递进而参与调控神经病理性疼痛(neuropathic pain,NP)的中枢敏化过程. 目的 探讨NP状态下脊髓小胶质细胞活化的分子机制. 内容 分别从脊髓小胶质细胞活化的胞外分子机制和胞内分子机制两方面就与此相关的研究进展作一综述. 趋向 小胶质细胞在NP中的作用将继续成为疼痛研究的热点,对小胶质细胞的深入研究可能使NP得到更为有效的治疗.     

胫骨癌痛大鼠脊髓背角5-羟色胺水平的变化

目的 评价胫骨癌痛大鼠脊髓背角5-羟色胺(5-HT)水平的变化.方法 雌性SD大鼠60只,体重160～180 g,采用随机数字表法,将其随机分为3组(n=20):对照组(C组)、假手术组(S组)和胫骨癌痛组(P组).C组不做任何处理;S组于右侧胫骨上段骨髓腔注射D-hank液10 μl;P组于右侧胫骨上段骨髓腔接种Walker 256大鼠乳腺癌细胞悬液10μl制备胫骨癌痛模型.于接种前1d、接种后3、5、7、9、11、14、16、18和21 d时测定机械痛阈.于接种前1 d、接种后7、14和21 d时,每组痛阈测定结束后随机处死大鼠4只,取脊髓组织,采用高效液相色谱法测定脊髓背角5-HT含量;接种后14 d取接种侧胫骨组织,光镜下观察胫骨破坏情况.脊髓背角5-HT含量与机械痛阈进行直线相关分析.结果 与C组和S组比较,P组接种后7～21 d时机械痛阈降低,接种后7、14和21 d时脊髓背角5-HT含量升高(P＜0.05),且5-HT含量与机械痛阈呈负相关(r=-0.973,P＜0.05).C组和S组各时点机械痛阈和脊髓背角5-HT含量比较差异无统计学意义(P＞0.05).光镜下P组大鼠术侧胫骨骨质严重破坏.结论 大鼠胫骨癌痛的形成与维持可能与脊髓背角5-HT水平升高有关.

Abstract：

Objective To investigate the change in 5-hydroxytryptomine (5-HT) content in spinal dorsal horn in a rat model of tibial bone cancer pain (BCP). Methods Sixty female SD rats weighing 160-180 g were randomly divided into 3 groups ( n = 20 each): control group (group C), sham operation group (group S) and BCP group. BCP was induced by intra-tibial inoculation of 10 μl Walker 256 breast cancer cell suspension in group BCP, while group S received intra-tibial inoculation of 10 μl D-hank solution. Paw withdrawal threshold to mechanical stimulation with yon Frey filaments (MWT) was measured 1 d before (baseline) and at 3, 5, 7, 9, 11,14, 16, 18 and 21 d after breast cancer cell inoculation. At 1 d before and 7, 14 and 21 d after breast cancer cell inoculation, four animals in each group were sacrificed after measurement of MWT. Their lumber segments of the spinal cord were removed for assay of 5-HT content in spinal dorsal horn using HPLC with fluorescence detector.HE staining was used to detect the damage to the tibia. Correlation between the 5-HT content and MWT was analyzed. Results MWT was significantly decreased after breast cancer cell inoculation in group BCP ( P ＜ 0.05).Microscopic examination showed serious bone destruction of tibia at the injection site in group BCP, while no bone destruction was found in groups C and S. 5-HT content in spinal dorsal horn was significantly higher in group BCP than in groups C and S (P ＜ 0.05). There was strong negative linear correlation between 5-HT content in spinal dorsal horn and MWT ( r = - 0.973, P ＜ 0.05 ). Conclusion The 5- HT content in spinal dorsal horn is significantly increased in rats with tibial BCP and is involved in the development of BCP.     

脊髓背角γ-氨基丁酸转运体-1在大鼠骨癌痛中的作用

目的 评价脊髓背角γ-氨基丁酸转运体-1 (GAT-1)在大鼠骨癌痛中的作用.方法 清洁级健康雌性SD大鼠80只,体重150～180 g,采用随机数字表法,将其随机分为5组(n=16):假手术组(Ⅰ组);骨癌痛组(Ⅱ组)采用胫骨上段骨髓腔接种Walker-256乳腺癌细胞的方法制备大鼠骨癌痛模型;假手术+ GAT-1选择性抑制剂NO-711组(Ⅲ组)和骨癌痛+NO-711(Ⅳ组)于术后第14天鞘内注射NO-711 20 μg,1次.d,连续3d;骨癌痛+生理盐水组(Ⅴ组)于术后第14天鞘内注射10μl生理盐水,1次/d,连续3d.于术前1d、术后第3、5、7、10、14、16天时测定大鼠机械痛阈,术后第16天机械痛阈测定后处死大鼠,取腰段脊髓,采用Western blot法检测脊髓GAT-1的表达,采用免疫荧光双标法观察Ⅰ组和Ⅱ组大鼠患侧脊髓GAT-1和星形胶质细胞标志物胶质纤维酸性蛋白(GFAP)免疫反应阳性产物的共表达.结果 与Ⅰ组和Ⅲ组比较,Ⅱ组、Ⅳ组和Ⅴ组术后第7～ 16天机械痛阈降低,Ⅱ组和Ⅴ组术后GAT-1表达上调(P＜0.05);与Ⅱ组和Ⅴ组比较,Ⅳ组术后第16天鞘内给药后机械痛阈升高,脊髓背角GAT-1表达下调(P＜0.05);与Ⅰ组比较,Ⅱ组患侧脊髓GFAP和GAT-1共表达增加(P＜0.05).结论 脊髓背角GAT-1的表达上调参与了大鼠骨癌痛的形成与维持,该作用可能与脊髓星形胶质细胞的活化有关.     

脊髓趋化因子配体2在大鼠胫骨癌痛中的作用

目的 探讨脊髓趋化因子配体2(CCL2)在大鼠骨癌痛中的作用.方法 健康成年雌性SD大鼠84只,体重160～ 180g,采用随机数字表法,将其随机分为3组(n=28):正常对照组(C组)、假手术组(S组)和骨癌痛组(P组).P组胫骨骨髓腔内注射Walker-256乳腺癌细胞混悬液制备大鼠胫骨癌痛模型;S组胫骨骨髓腔内注射生理盐水;C组不作任何处理.于接种前ld、接种后l、3、7、10、14和21 d时,测定机械性刺激阈值.于接种前ld、接种后7、14和21'd时痛阈测定结束后,各组随机处死6只大鼠,取L4～6脊髓组织,采用ELISA法测定CCL2含量,反映其表达.接种后14 d时痛阈测定结束后,P组随机取4只大鼠,采用免疫荧光双标染色法观察脊髓背角CCL2与离子钙接头蛋白分子-1(小胶质细胞特异性标记物)、胶质纤维酸性蛋白(星形胶质细胞特异性标记物)和神经元特异核蛋白(神经元特异性标记物)的共表达情况.结果 与C组和S组相比,P组接种后7～21 d时机械性刺激痛阚下降,接种后7、14和21 d时脊髓CCL2表达上调(P＜0.05).骨癌痛大鼠脊髓背角CCL2在小胶质细胞和星形胶质细胞中存在表达,而在神经元中无表达.结论 脊髓小胶质细胞和星形胶质细胞中释放的CCL2参与了大鼠胫骨癌痛的发生发展.