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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 study the protective effect of glicorol on diabetic neuropathy and to explore its possible mechanism. Methods: One-time tail vein injection of STZ 25 mg / kg was given to rats with type 2 diabetes mellitus for four weeks after being given high-fat diet. The successful animals were randomly divided into groups according to their blood glucose level and body weight. 8 weeks, to investigate the local sciatic nerve blood flow, pathological morphology and blood lipid levels and other indicators. The rats were injected subcutaneously with L-glutamate (MSG) 5g / kg on the second day of birth every other day for 3 times to replicate obese insulin-resistant rats. At 8 weeks of age, the obese animals were randomly divided into groups and administered orally for 4 consecutive weeks to detect insulin sensitivity related indicators. In addition, the effects of gliclazide on blood glucose and glucose tolerance in normal mice were also studied. RESULTS: After 8 weeks of administration, the Flux, Conc and Speed of the sciatic nerve decreased significantly in the diabetic model group, while the levels of serum LDL, HDL, Total cholesterol (TC) and triglyceride (TG) increased. Electron microscopy results showed that the lamina propria of the myelinated fibers in the model group was stratified, the vacuoles and swelling were exfoliated, and the nuclear chromatin breakdown , Compared with the normal group there was a significant difference. The dose of 0.225g / kg of gepirone can reduce the sciatic nerve lesion in rats. Compared with the model group, the difference was statistically significant. Gemcitabine at 0.225g / kg and 0.1125g / kg could significantly improve the local blood flow index of sciatic nerve. Each dosage of kespene Ketone significantly reduced the levels of LDL and TG; Lee’s index of MSG rats increased, serum insulin level increased, GIR decreased significantly; GIR value of rats, but gabolone had no significant effect on the blood glucose and glucose tolerance of normal mice. CONCLUSION: Maggisone has a protective effect on the structure and function of peripheral nerves in diabetic rats. These effects may be related to the improvement of blood lipid metabolism, the increase of nutrition blood flow around nerve tissue and the improvement of insulin resistance in diabetic rats.