姜黄素对糖尿病痛性周围神经病变大鼠脊髓黄嘌呤氧化酶活性的影响

The effects of curcumin on the activity of spinal cord purine oxidase in rats with painful diabetic neuropathy

目的 评价姜黄素对糖尿病痛性周围神经病变大鼠脊髓黄嘌呤氧化酶（XOD）的影响.方法 腹腔注射1%链脲佐菌素（STZ）60 mg/kg诱导大鼠糖尿病痛性周围神经病变模型,在造模成功的痛过敏糖尿病大鼠中取20只随机分为糖尿病组（DPN组,n=10）和姜黄素治疗组（CUR组,n=10）,另取10只同月龄大鼠为正常对照组（NSC组,n=10）,给予腹腔注射等剂量的枸橼酸-枸橼酸钠缓冲液.CUR组、DPN组在第28天后分别每天灌胃给予200 mg/kg的姜黄素和等剂量的生理盐水2周.于注射STZ前（T1）,注射STZ后2、7、14、21、28、35、42 d（T2～8）取尾静脉血0.1 mL测定血糖浓度;于T1、T3～8时测定大鼠右后爪机械缩足反应阈值（PWT）;T8时处死大鼠,取腰段脊髓检测XOD的活性.结果 与NSC组比较,DPN和CUR组大鼠于T2～8时血糖浓度升高（P〈0.01）,于T5-8体重下降（P〈0.05）,于T4～8时PWT降低（P〈0.05）;与DPN组比较,CUR组T1～8时血糖浓度无显著变化（P〉0.05）,T1～6时PWT无显著变化（P〉0.05）,T7、8时PWT升高（P〈0.05）;与T1时比较,T2～8时DPN和CUR组血糖浓度升高（P〈0.01）;与T6时比较,T7、8时CUR组PWT升高（P〈0.05）.与NSC组比较,DPN和CUR组大鼠脊髓XOD活性升高（P〈0.01）;与DPN组比较,CUR组大鼠脊髓XOD活性下降（P〈0.01）.结论 姜黄素改善糖尿病痛性周围神经病变大鼠的疼痛,其机制可能与抑制脊髓XOD的活性有关.

Objective To evaluate the effects of curcumin on spinal cord purine oxidase （XOD） in streptozotocin （STZ） - induced diabetic rats with painful diabetic neuropathy. Methods Painful diabetic neuropathy was induced by intraperitoneal injection with 1% STZ （60 mg/kg） in Sprague - Dawley rats. After the onset of hypoalgesia, these diabetic rats were randomly allocated to diabetic group （DPN group, n = 10） and curcumin group （CUR group, n = 10）. Another 10 age- matched normal rats were served as control group （NSC group, n = 10）. The rats in CUR group and DPN group received daily lavage of curcumin （200 mg/kg） and normal saline, respectively, for 14 consecutive days 28 days af- ter STZ injection. Blood samples were collected from vena caudalis to assess the blood glucose level before STZ injection （T1） and 2, 7, 14, 21,28,35, and 42 days after STZ injection （T2 to T8, respectively）. Responses to the mechanical stimulus were measured with von Frey filament, while paw withdraw thresholds （PWTs） were recorded. The rats were sacrificed for collection of and lumbar segment of spinal cord and assessment of the activity of XOD. Results Compared to NSC group, rats in both CUR and DPN groups showed significant hyperglycemia since T2 （P 〈0. 01 ）, and reduction of body weight （P 〈 0. 05 ） and lower PWT since T4 （P 〈 0. 05 ）. There was no significant difference between CUR and DPN group in blood sugar or body weight at T1 - T8 （P 〉 0. 05 ）, or in PWT at T1 - T6 （P 〉 0. 01 ）. Compared to DPN group, significantly higher PWT at T7 and T8 in CUR group （P 〈 0. 05）. Compared to NSC group, the spinal cord XOD activity was significantly increased in both DPN and CUR groups （P 〈 0. 01 ）, while it was significantly more prominent in DPN group （P 〈 0. 01 ）. Conclusion Curcumin attenuated diabetic neuropathic pain in rats by inhibition of XOD activity in spinal cord.