温经通络散对奥沙利铂所致周围神经毒性大鼠的作用机制的研究.docVIP

温经通络散对奥沙利铂所致周围神经毒性大鼠的作用机制的研究 　　摘要：目的 探讨温经通络散外用对奥沙利铂所致周围神经毒性大鼠的治疗作用及机制。方法 采用腹腔注射奥沙利铂4 mg/kg建立标准奥沙利铂周围神经毒性大鼠模型。将雌性Wistar大鼠随机分为正常组、模型组、中药组，中药组予温经通络散浸泡大鼠四肢及尾部，模型组大鼠予去离子水浸泡作为对照，正常组大鼠腹腔注射等体积5%葡萄糖。检测温度和机械刺激下大鼠痛觉超敏和过敏反应，采用免疫组化方法检测大鼠L4～L6段脊髓背角GFAP表达，RT-PCR检测大鼠L4～L6段背根神经节谷氨酸转运体1（GLT-1）mRNA表达。结果 模型组大鼠较正常组出现明显行为学改变（P0.05），中药组大鼠较模型组行为学明显改善（P0.01）；模型组大鼠GFAP阳性细胞数较正常组明显升高（P0.05），中药组升高不明显；与正常组比较，模型组可见脊髓背角内星形胶质细胞胞体增大，突起增多、变粗及GLT-1 mRNA表达下降（P0.05，P0.01）；与模型组比较，中药组活性细胞减少、突起减少及GLT-1 mRNA表达水平升高（P0.01）。结论 温经通络散外用可显著改善奥沙利铂所致的神经病理性疼痛。其作用机制可能与抑制脊髓背角星形胶质细胞活化进而介导的伤害性信号传递有关。 　　关键词：温经通络散；奥沙利铂；周围神经毒性；神经病理性疼痛；中医外治；行为学；大鼠 　　DOI：10.3969/j.issn.1005-5304.2015.020 　　中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2015）04-0070-04 　　Effects of Wenjing Tongluo Formula on GFAP Level in Perpheral Neuropathy Rats WANG Yuan-yuan1， JIA Li-qun2， DENG Bo2， ZHANG Hong-lei2， SONG Ai-ping2， DA Ji-ping2， YU Li-li2 （1.Beijing University of Chinese Medicine， Beijing 100029， China；2.China-Japan Friendship Hospital， Beijing 100029， China） 　　Abstract：Objective To discuss the treatment action and mechanism of Wenjing Tongluo Formula on oxaliplatin-induced perpheral neurotoxicity in rats. Methods Intraperitoneal injection was used to inject oxaliplatin 4 mg/kg to establish oxaliplatin-induced peripheral neurotoxicity rat models. Female Wistar rats were randomly divided into normal group， model group， and TCM group. TCM group was given Wenjing Tongluo Formula to soak rats’ limbs and tails. Rats in the model group were soaked with deionized water for comparison. Rats in the normal group received intraperitoneal injection with 5% glucose. Algesia hypersensitivity and anaphylaxis were detected under the mechanical stimulation and temperature. Immunohistochemical method was used to detect the expression of GFAP in L4-L6 spinal dorsal horn of rats. Explore the level of GLT-1 in L4-L6 dorsal root ganglia by RT-PCR. Results Rats in model group showed obvious behavioral changes compared with normal group （P 　　基金项目：国家自然科学基金