中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
1期
118-121
,共4页
金迪%杨建平%胡计嬅%王丽娜
金迪%楊建平%鬍計嬅%王麗娜
금적%양건평%호계화%왕려나
骨肿瘤%疼痛%1-磷脂酰肌醇3-激酶%蛋白质丝氨酸苏氨酸激酶%小胶质细胞%脊髓%信号通路
骨腫瘤%疼痛%1-燐脂酰肌醇3-激酶%蛋白質絲氨痠囌氨痠激酶%小膠質細胞%脊髓%信號通路
골종류%동통%1-린지선기순3-격매%단백질사안산소안산격매%소효질세포%척수%신호통로
bone neoplasms%pain%1-phosphatidyli-nositol 3-kinase%protein-serine-threonine kinases%mi-croglia%spinal cord%signaling pathway
目的：观察鞘内注射( intrathecal injection,i. t.)磷脂酰肌醇3-激酶( PI3K)抑制剂LY294002对骨癌痛大鼠疼痛行为学、脊髓背角磷酸化Akt ( p-Akt )表达的影响。方法♀SD大鼠40只,体质量180~200 g,随机分为5组(n=8)：假手术组(Ⅰ组)、假手术+LY294002组(Ⅱ组)、骨癌痛组(Ⅲ组)、骨癌痛+二甲基亚砜( DMSO )组( IV 组)、骨癌痛+LY294002(V 组),于大鼠左侧胫骨干骺端骨髓腔内注射Walker256乳腺癌细胞构建胫骨癌痛模型。术后d 7~9鞘内连续注射浓度为2．5 g·L-1的LY29400210μL 或10μL 的5%DMSO。观测术前及术后d 7给药后每小时机械痛阈(至8 h)。术后d 9处死大鼠,取各组大鼠的L4~6脊髓组织进行免疫组化染色,检测脊髓背角PI3K 活化标志p-Akt 的表达。结果骨癌痛组大鼠(Ⅲ、Ⅳ、Ⅴ组)机械痛阈(MWT)明显低于假手术组(Ⅰ组)(P <0．01),V 组在给药后2~4h 痛阈明显升高(P <0．05),3 h 达到峰值(P <0．01)。与Ⅰ组比较,Ⅲ、Ⅳ组脊髓背角p-Akt 阳性细胞数明显增加,p-Akt 表达增多( P <0．01)。与Ⅲ、Ⅳ组比较,Ⅴ组鞘内注射 LY294002后能明显降低脊髓背角p-Akt 的表达(P <0．05)。结论 PI3K/ Akt 通路可能参与大鼠骨癌痛的发生。
目的：觀察鞘內註射( intrathecal injection,i. t.)燐脂酰肌醇3-激酶( PI3K)抑製劑LY294002對骨癌痛大鼠疼痛行為學、脊髓揹角燐痠化Akt ( p-Akt )錶達的影響。方法♀SD大鼠40隻,體質量180~200 g,隨機分為5組(n=8)：假手術組(Ⅰ組)、假手術+LY294002組(Ⅱ組)、骨癌痛組(Ⅲ組)、骨癌痛+二甲基亞砜( DMSO )組( IV 組)、骨癌痛+LY294002(V 組),于大鼠左側脛骨榦骺耑骨髓腔內註射Walker256乳腺癌細胞構建脛骨癌痛模型。術後d 7~9鞘內連續註射濃度為2．5 g·L-1的LY29400210μL 或10μL 的5%DMSO。觀測術前及術後d 7給藥後每小時機械痛閾(至8 h)。術後d 9處死大鼠,取各組大鼠的L4~6脊髓組織進行免疫組化染色,檢測脊髓揹角PI3K 活化標誌p-Akt 的錶達。結果骨癌痛組大鼠(Ⅲ、Ⅳ、Ⅴ組)機械痛閾(MWT)明顯低于假手術組(Ⅰ組)(P <0．01),V 組在給藥後2~4h 痛閾明顯升高(P <0．05),3 h 達到峰值(P <0．01)。與Ⅰ組比較,Ⅲ、Ⅳ組脊髓揹角p-Akt 暘性細胞數明顯增加,p-Akt 錶達增多( P <0．01)。與Ⅲ、Ⅳ組比較,Ⅴ組鞘內註射 LY294002後能明顯降低脊髓揹角p-Akt 的錶達(P <0．05)。結論 PI3K/ Akt 通路可能參與大鼠骨癌痛的髮生。
목적：관찰초내주사( intrathecal injection,i. t.)린지선기순3-격매( PI3K)억제제LY294002대골암통대서동통행위학、척수배각린산화Akt ( p-Akt )표체적영향。방법♀SD대서40지,체질량180~200 g,수궤분위5조(n=8)：가수술조(Ⅰ조)、가수술+LY294002조(Ⅱ조)、골암통조(Ⅲ조)、골암통+이갑기아풍( DMSO )조( IV 조)、골암통+LY294002(V 조),우대서좌측경골간후단골수강내주사Walker256유선암세포구건경골암통모형。술후d 7~9초내련속주사농도위2．5 g·L-1적LY29400210μL 혹10μL 적5%DMSO。관측술전급술후d 7급약후매소시궤계통역(지8 h)。술후d 9처사대서,취각조대서적L4~6척수조직진행면역조화염색,검측척수배각PI3K 활화표지p-Akt 적표체。결과골암통조대서(Ⅲ、Ⅳ、Ⅴ조)궤계통역(MWT)명현저우가수술조(Ⅰ조)(P <0．01),V 조재급약후2~4h 통역명현승고(P <0．05),3 h 체도봉치(P <0．01)。여Ⅰ조비교,Ⅲ、Ⅳ조척수배각p-Akt 양성세포수명현증가,p-Akt 표체증다( P <0．01)。여Ⅲ、Ⅳ조비교,Ⅴ조초내주사 LY294002후능명현강저척수배각p-Akt 적표체(P <0．05)。결론 PI3K/ Akt 통로가능삼여대서골암통적발생。
Aim To investigate the effect of intrathecal injection of PI3 K inhibitor LY294002 on pain behav-iour and expression of p-Akt in spinal dorsal horns in bone cancer pain( BCP) rats. Methods Forty female SD rats weighing 180~200 g were randomly divided in-to five groups ( n =8 each ):(Ⅰ) sham group;(Ⅱ) sham+LY294002 group;(Ⅲ) BCP group;(Ⅳ) BCP+DMSO group;( V) BCP+LY294002 group. BCP rat model was induced by inoculating Walker 256 mamma-ry gland carcinoma cells into the medullary cavity of the left tibia. Rats received i. t. injections of either PI3 K inhibitor LY294002 10μL ( 2. 5 g · L-1 ) or 5%DMSO 10 μL at the time of d 7~9 after the operation. Mechanical withdrawal threshold( MWT) test was per-formed before and after i. t. injections on d7(till 8h). The rats were sacrificed after inoculation and the L4~6 segments of the spinal cords were removed for immu-nohistochemistry to determinate the expression changes of spinal p-Akt. Results Compared with I group, the rats inⅢ,Ⅳ,Ⅴgroup showed obvious mechanical hy-peralgesia. The MWT of V group increased apparently from 2nd hour to 4th hour(P<0. 05),and reached the peak in 3rd hour(P<0. 01). Compared with I group, the expression of p-Akt in the spinal cord in Ⅲ,Ⅳgroup increased obviously ( P <0. 01 ) . Compared withⅢ,Ⅳ group,i. t. injections of LY294002 obviously cut down the expression of p-Akt in the spinal cord ( P <0. 05). Conclusion PI3K/Akt singaling pathway may take part in the development of bone cancer pain.
