丹参酮ⅡA抑制长春新碱诱导化疗痛维持期痛觉过敏及其机制

Suppressive Effect of Tanshinone ⅡA on hyperalgesia in the maintenance phase of Vincristine-induced neuropathic pain in rats and its mechanism

目的探讨丹参酮ⅡA对长春新碱诱导化疗痛维持期痛觉过敏的抑制作用及其机制。方法 SD大鼠50只,采用随机数字表法分为5组(每组10只):对照组(Control);化疗痛组(CINP);化疗痛+丹参酮ⅡA10mg/kg组(CINP+Tan10);化疗痛+丹参酮ⅡA20 mg/kg组(CINP+Tan20);化疗痛+丹参酮ⅡA50 mg/kg组(CINP+Tan50)。大鼠进行隔日腹腔注射125μg/kg长春新碱(共计7次)建立化疗药物诱导的神经病理性疼痛动物模型,第8天开始采用不同剂量的Tanshinone ⅡA治疗大鼠。对照组和化疗痛组用生理盐水(腹腔注射,5ml/kg)。给药前和给药后1、7、9、10、14天分别采用机械缩足反射阈值(MWT)和热缩足反射潜伏期(TWL)评价大鼠机械痛敏和热痛敏;给药后14天采用Western blotting法检测脊髓GFAP和OX42蛋白表达;ELISA法检测脊髓TNF-α,IL-6蛋白表达。结果与Control组比较,CINP组大鼠给药后9、10、14天MWT和TWL值明显降低(P<0.001);与CINP组比较,CINP+Tan20组和CINP+Tan50组大鼠在给药后9、10、14天MWT和TWL值明显升高(P<0.01;P<0.001),并且CINP+Tan20组和CINP+Tan50组差异具有统计学意义(P<0.05;P<0.01);与Control组比较,CINP组大鼠在给药后14天脊髓GFAP蛋白和TNF-α,IL-6表达明显升高(P<0.01,P<0.01);与CINP组比较,CINP+Tan20组和CINP+Tan50组大鼠在给药后14天脊髓GFAP蛋白和TNF-α,IL-6表达明显降低(P<0.05,P<0.01),并且CINP+Tan20组和CINP+Tan50组差异具有统计学意义(P<0.05)。结论丹参酮ⅡA能够抑制化疗痛维持期大鼠机械痛觉过敏和热痛觉过敏,其作用机制可能与其抑制大鼠脊髓星型胶质细胞活化,进而减少炎性细胞因子TNF-α,IL-6的表达相关。

Objective To observe the inhibited effect of TanshinoneⅡA on hyperalgesia in the maintenance phase of Vincristine-induced neuropathic pain in rats and its mechanism.Methods Fifty male Sprague-Dawley rats were randomly divided into 5 groups(n=10):control group(Control);CIPN group(CIPN);CINP+TanshinoneⅡA10 mg/kg(CIPN+Tan10);CINP+TanshinoneⅡA20 mg/kg(CIPN+Tan20);CINP+TanshinoneⅡA50 mg/kg(CIPN+Tan50).Vincristine 125μg/kg was administered intraperitoneally(i.p.)on alternate days for 14 days to establish chemotherapy-induced neuropathic pain models,rats in TanshinoneⅡA treatment groups were treated with different doses of TanshinoneⅡA for 7 consecutive days from the 8 th day after the first Vincristine,while those in the control group and CINP group were given normal saline.on the 14 th d of modeling.Mechanical allodynia and heat hyperalgesia were evaluated by mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)respectively before and on days 1,7,9,10,and 14 after vincristine;on day 14 after vincristine,protein expressions of GFAP and OX42 were detected by Western blotting,and tumor necrosis factor(TNF-α)and IL-6 protein expression was determined by ELISA.Results On days 9,10,and 14 after vincristine,Rats in CINP group had significantly decreased as compared with Control group(P<0.001);while,Rats in CIPN+Tan20 and CIPN+Tan50 group showed a obviously increased MWT and TWL as compared with CIPN group(P<0.01,P<0.001)and there were significant difference CIPN+Tan20 and CIPN+Tan50 group(P<0.05,P<0.01).On days 14 after vincristine,Rats in CINP group had significantly increased protein expressions of GFAP,TNF-α,and IL-6)as compared with Control group(P<0.01);Rats in CIPN+Tan20 and CIPN+Tan50 group showed an obviously decreased protein expressions of GFAP,TNF-α,and IL-6 as compared with CIPN group(P<0.05,P<0.01)and there were significant difference between CIPN+Tan20 and CIPN+Tan50 group(P<0.05).Conclusion TanshinoneⅡA can inhibit the chemotherapy-induced neuropathic pain,probably by inhibiting the activation of astroglial cells in the spinal cord,and then reducing the expression of TNF-αand IL-6.