鞘内注射芬太尼对糖尿病周围神经病变大鼠脊髓TNF-α表达的影响  

Effects of Fentanyl Intrathecally Administered on TNF-α Expression in Spinal Cord of Diabetic Rats with Peripheral Neuropathy

作　　者：马国平[1,2] 杨京利[2] 田玉科[1] 刘菊英[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉科,武汉430030 [2]郧阳医学院附属太和医院麻醉科,湖北十堰442000

出　　处：《医药导报》2009年第8期1003-1006,共4页Herald of Medicine

摘　　要：目的观察芬太尼对糖尿病周围神经病变模型大鼠脊髓肿瘤坏死因子α(TNF-α)表达的影响,以及其脊髓保护作用,探讨其镇痛机制。方法成年雌性Wistar大鼠70只,随机取10只设为正常对照组(A组),腹腔注射0.9%氯化钠溶液3mL·kg-1·d-1;其余大鼠腹腔注射链脲菌素(STZ)建立糖尿病模型,得48只糖尿病模型大鼠。对照组和糖尿病模型大鼠实施鞘内置管,分别成功8只和32只。A组8只鞘内各注射0.9%氯化钠注射液10μL;将糖尿病大鼠随机等分为2组,糖尿病对照组(B组)16只鞘内注射与A组等体积0.9%氯化钠注射液;芬太尼治疗组(C组)16只鞘内注射芬太尼0.5μg·(10μL)-1;于给药后第1,2,3,4周分别进行行为学测定,记录机械缩足阈值;取脊髓切片,用尼氏染色法观察脊髓的病理形态学改变;应用免疫组化方法和图象分析系统检测脊髓背角TNF-α的表达。结果与A组比较,B、C组大鼠机械缩足阈值降低(均P<0.05),脊髓背角组织中TNF-α表达显著升高(均P<0.01);与B组比较,C组机械缩足阈值升高(P<0.05),TNF-α表达显著降低(P<0.01)。尼氏染色显示,B组大鼠脊髓尼氏小体呈现破碎和溶解性改变,鞘内注射芬太尼可改善尼氏小体的变化。结论糖尿病大鼠周围神经病变引起的神经痛与脊髓背角促炎性细胞因子TNF-α有关。鞘内注射芬太尼对脊髓有保护作用,并可明显抑制脊髓背角TNF-α的表达,减轻糖尿病神经痛。Objective To investigate the effect of fentanyl on the expression of TNF-α in spinal cord and its protective effect on diabetic rats with peripheral neuropathy. Methods Normal rats injected intratheeally with 0.9% sodium chloride 10 μL was as a normal control （ group A）. STZ-induced diabetic rats with an intrathecal catheter were allocated to two groups randomly： 16 diabetic rats received 10 μL 0.9% normal saline as group B, another 16 received fentanyl at 0.5 μg · （10 μL） -1 injected intrathecally via an intrathecal catheter once a day as group C. The treatment lasted for 4 weeks. Paw withdrawal mechanical threshold was measured by using the up/down method with von Frey monofilaments at 1th, 2th, 3th, 4th week since the treatment started. TNF-α expression on cornu dorsale medullae spinalis was detected by immunohistochemistry and image analysis, and spinal pathomorphism was measured by Nissl＇s staining. Results Compared with group A, the paw withdrawal mechanical thresholds in group B and C were markedly lowered （ P 〈 0.05 ）, while expressions of TNF-α in spinal cord were significantly increased （P 〈 0.01 ）. The paw withdrawal mechanical threshold in group C was raised （P 〈 0.05 ） and expression of TNF-α was significantly lower in comparison to group B （P 〈 0.01 ）. Nissl＇s granules appeared to be broken and thawed in diabetic rats, however, which were improved by intrathecal injection of fentanyl. Conclusion The cause of neuropathic pain by diabetes with peripheral neuropathy is associated with overexpression of TNF-α in spinal cord. Intrathecal injection of fentanyl reduces the expression of TNF-α, protects the spinal cord and relieves peripheral neuropathic pain in diabetic rats.

关 键 词：芬太尼 糖尿病 神经痛 尼氏小体 肿瘤坏死因子-α 

分 类 号：R971.2[医药卫生—药品] R965[医药卫生—药学]