氯胺酮对糖尿病大鼠神经功能及神经病理痛的作用

目的探讨氯胺酮对糖尿病大鼠神经功能及神经病理痛的疼痛作用。方法雌性Wistar大鼠24只，体重180—220g，随机分为3组（n=8）：正常组（N组）、糖尿病神经病理性痛组（D组）、氯胺酮组（K组）。D组、K组腹腔注射链脲菌素65mg／kg制作糖尿病神经病理痛模型，大鼠自由进食饮水饲养4周。自第5周开始，K组大鼠腹腔注射10mg／kg氯胺酮，1次／d，持续4周。随后测定各组大鼠机械痛阈值（MWT）、神经传导速度（NCV）。并用砂罗铬花青法行神经髓鞘染色和缓冲亚甲蓝法进行尼氏体染色。应用ELISA法测定脊髓内超氧化物歧化酶（SOD）、丙二醛（MDA）含量。结果D组脊髓和DRG神经元的尼氏体体积减小，并且有尼氏体的脱失和溶解。坐骨神经的髓鞘存在不同程度的水肿，空泡样变性，结构紊乱和局灶性脱失。K组髓鞘及尼氏体病变明显减轻。与N组比较，D、K组大鼠MWT、NCV、SOD降低，MDA升高（P〈0．05）；与D组比较，K组大鼠MWT、NCV、SOD升高，MDA降低（P〈0．05）。结论氯胺酮通过抗氧化对糖尿病神经病理痛大鼠有神经保护及疼痛治疗作用。

Role of ketamine on the nerve function and neuropathic pain in diabetic rats

Objective To investigate the role of ketamine on the nerve function and neuropathie pain in diabetic rats. Methods 24 female Wistar rats weighing 180 - 220 g were randomized into 3 groups （ n = 8 ） ： normal control group （group N）, diabetic neuropathic pain group （group D） and ketamine group （group K）. Diabetic neuropathic pain model was induced by intraperitoneal streptozocin 65 mg/kg in groups D and K, in which rats were housed with food and water ad libitum for 4 weeks. From the 5th week the rats in group K received ketamine 10 mg/kg intraperitoneally once a day for another 4 weeks. At the end of the 8th week, mechanical withdrawal threshold （WMT） and nerve conduction velocity （NCV） were measured. Myelin sheath of sciatic nerve and Nissl bodies in neurons were demonstrated with staining of soleehrome eyanin and buffered methylene blue, respectively. The levels of superoxide dismutase （SOD） and malonaldehyde （MDA） in the spinal cord were assayed by ELISA. Results The Nissl bodies in the spinal cord and the DRG neurons were observed to have pyknosis, accompanied by collapse and karyolysis of Nissl body. The myelin sheath of the sciatic nerve was characterized by edema of different degrees, vacuole - like denaturation, structural derangement and local demyelination. The neuropathies in myelin sheath and Nissl body were markedly attenuated in group K. Compared with group N, the levels of WMT, NCV and SOD were lower and MDA level higher in groups D and K （ P 〈 0.05 ） , while the comparison between the latter two groups revealed that groups K had higher levels of WMT, NCV and SOD and the lower MDA level. Conclusion Ketamine protects nerve and relieves the painful symptoms of neuropathic pain in diabetic rats by its antioxidative effect.