帕罗西汀对糖尿病大鼠神经病理性疼痛的影响及其作用机制

目的 探讨帕罗西汀对糖尿病大鼠神经病理性疼痛的影响及其可能的作用机制。方法 将健康成年♂SD大鼠随机分为3组，每组8只，包括正常对照组、糖尿病组、糖尿病+帕罗西汀治疗组。采用链脲佐菌素（75 mg·kg^-1）一次性腹腔注射建立糖尿病模型，并分别于注射前、注射后7，14，28 d检测机械性缩足反应痛阈（PWMT）。于注射佐脲酶菌素28 d后处理大鼠；取L₄~L₆段脊髓，运用尼氏体染色法检测脊髓组织的形态变化，TUNEL染色检测背角脊髓神经元的凋亡情况，免疫印迹技术检测脊髓神经元血红素加氧酶-1（HO-1）的表达。结果 与正常对照组比较，糖尿病组和糖尿病+帕罗西汀治疗组机械性痛阈明显降低（P<0.05）；与糖尿病组比较，糖尿病+帕罗西汀治疗组大鼠在注射佐脲酶菌素后28 d机械性痛阈显著升高（P<0.05）。糖尿病组大鼠脊髓背角萎缩，神经元变性坏死，细胞数降低，并且尼氏体减少，甚至消失；而糖尿病+帕罗西汀治疗组相对于糖尿病组大鼠脊髓背角萎缩降低，神经元数量升高，可见尼氏体。正常对照组大鼠脊髓背角神经元有较多HO-1表达，而糖尿病组HO-1表达量较低；相对于糖尿病组，糖尿病+帕罗西汀治疗组大鼠脊髓背角神经元有大量HO-1表达。结论 帕罗西汀可以减轻糖尿病大鼠神经病理性疼痛，对脊髓背角神经元具有保护作用，其作用机制可能与上调脊髓背角神经元HO-1的表达有关。

Protective Effects of Paroxetine on Neuropathic Pain in Diabetic Rats and the Possible Mechanism

OBJECTIVE To observe the protective effects of paroxetine (PAT) on neuropathic pain in diabetic rats and to research the possible mechanism. METHODS Twenty-four male SD rats were randomly divided into three groups (n=8):control group, diabetes mellitus (DM) group and DM+PAT group. Diabetes mellitus was induced via single intraperitoneal injection of streptozotocin (STZ) at a dose of 75 mg·kg^-1. Paw withdrawal mechanical threshold (PWMT) was measured before modeling and on 7, 14 and 28 d after STZ injection. On day 28 after STZ injection, all rats were sacrificed, lumbar segments (L₄-L₆) of spinal cord were recovered for pathologic observation. Paraffin slides of the spinal cord were prepared with Nissl''s staining for detecting the pathologic changes. Apoptosis in dorsal horn spinal cord neurons was detected by TUNEL staining. Western blot was used to detect the expression levels of HO-1 in spinal cord. RESULTS Pain threshold to mechanical stimuli in DM group and DM+PAT group was significantly decreased compared with control group (P<0.05), while rats in DM+PAT group had higher threshold to mechanical stimuli on day 28 after STZ injection than rats in DM group (P<0.05). Microscopic examination showed that dorsal horn of the spinal cord in DM group was atrophic; the number of neurons was significantly decreased and the Nissl''s bodies in spinal cord were diminished, while these changes in DM+PAT group were significantly weakened. The expression levels of HO-1 in spinal cord in DM+PAT group were significantly increased compared with DM group. CONCLUSION Paroxetine can attenuate neuropathic pain in diabetic rats and protect the neurons in spinal cord, the possible mechanism may be explained by increasing the expression of HO-1 in spinal dorsal horn.