参葛酚酮对糖尿病神经病变的保护作用研究

Studies on the effects of Shengefentong on diabetie neuropathy in animals

目的:研究参葛酚酮对糖尿病神经病变的保护作用并探讨其可能的作用机制。方法:连续4周给予高脂饲料后一次性尾静脉注射STZ 25mg/kg复制Ⅱ型糖尿病大鼠模型,将造模型成功的动物按血糖值和体重随机分组,灌胃给药,每天一次,连续8周,考察坐骨神经局部血流量、病理形态以及血脂水平等指标。大鼠出生第二天皮下注射L-谷氨酸钠(MSG)5g/kg隔天一次,共3次,复制肥胖型胰岛素抵抗大鼠。8周龄时将肥胖动物随机分组,灌胃给药,连续4周,检测胰岛素敏感性相关指标。另外还研究了参葛酚酮对正常小鼠血糖和糖耐量的影响。结果:给药8周后,糖尿病模型组大鼠坐骨神经局部血流量(Flux)、血细胞聚集值(Conc)、流速(Speed)显著减少,血清低密度胆固醇(LDL)、高密度胆固醇(HDL)、总胆固醇(TC)以及甘油三酯(TG)上升;电镜观察结果显示,模型组有髓神经纤维出现纤维的板层结构分层、空泡和肿胀甚者髓鞘脱落,许旺细胞核染色质分解,与正常组比较有显著性差异。参葛酚酮0.225g/kg能够减轻大鼠坐骨神经病变,与模型组比较差异具有统计学意义,参葛酚酮0.225g/kg、0.1125 g/kg组能明显改善上述坐骨神经局部血流指标;参葛酚酮各个剂量均能显著的降低LDL和TG水平;MSG大鼠Lee's指数增加,血清胰岛素水平升高,葡萄糖输注速率(GIR)显著降低;参葛酚酮各剂量组能显著升高MSG大鼠GIR值,但参葛酚酮对正常小鼠血糖、糖耐量均无明显影响。结论:参葛酚酮对糖尿病周围神经的结构和功能有保护作用,这些作用可能与其能够改善糖尿病大鼠血脂代谢、增加神经组织周围营养性血流量以及改善胰岛素抵抗作用有关。

Objective： To investigate the protective effect and its mechanisms of shengefentong （SGFY） on the diabetic neuropathy. Methods： Type 2 diabetes mellitus were induced by high-fat-diet for 4 weeks and iv Streptozotocin （ST-Z） 25mg/kg once in SD rats. These rats which blood glucose were higher than 13.7 mmol/L were randomly divided into 5 groups and were intregastric administration of Meffofinin Hydrochl- oride O. 125 g/kg,SGFT 0. 1125 g/kg, SGFT 0. 225 g/kg, SGFr 0.45 g/kg or the same volume of solvent respectively, once a day for 8 weeks. After the last treatment, the local blood flow around the sciatic nerve were measured; the sciatic nerves were observed using electron microscopy and the levels of blood lipid were also measured in rats. Neonatal rats treated with monosodium glutamate （MSG） 5g/kg every other day, three times, to induce obesity. 8 weeks later, MSG rats were randomly divided into 5 groups and were intregastric administration of rosiglitazone 2.7mg/kg, SGFr 0.117 g/kg, SGFT 0.234 g/kg, SGFT 0.468 g/kg or the same volume of solvent respectively,once a day for 4 weeks. Then the insulin sensitivity index and the insulin concentration in blood were measured. Also, the effects of SGFT on the glucose tolerance and levels of blood glucose in normal mice were detected. Results： 8 weeks after administration, the blood flux, speed and Conc a- round the sciatic nerve were reduced, but the levels of HDL, LDL, TG, TC were increased in the serum in type 2 diabetic rats. Under elec- tron microscope observation, the myelinated nerve fibers＇hierarchical structure has separated, swelling, even the shedding of the myelin sheath were seen. Besides, the nucleus chromatins were decomposition in schwann cells in the model group. SGFT 0.225 g/kg improved the pathological changes of sciatic nerve and reduced the levels of LDL and TG in type 2 diabetes rats. SGFY 0.225 g/kg and 0.1125 g/kg can significantly improve the local blood flow around sciatic nerve. The Lee＇s index and insulin levels were significantly higher in MSG rats, meanwhile the GIR was the contrary. SGFT significantly increased the GIR in MSG rats. But it had no significantly effect on glucose tolerance and the level of blood glucose in normal mice. Conclusion： SGFT has a protective effect on the structure and function of diabetic neuropathy nerve. These effects may be related to improve the blood lipid metabolism, insulin resistance, and increase the flow of blood around the nerv- ous tissue.