The effect and mechanism of N-(Z)-9-octadecenyl-2-propanesulfonamide in treatment of insulin resistance in type 2 diabetic mice

探索新化合物N-(Z)-9-十八烯基-2-丙磺酰胺(N15)对2型糖尿病(T2DM)胰岛素抵抗小鼠的影响并探讨其可能作用机制。采用链脲佐菌素(S; TZ)连续小剂量腹腔注射诱导T2DM小鼠模型, N15(50、100和200 mg·kg~(-1)·d~(-1))和吡格列酮(6; mg·kg~(-1)·d~(-1))连续灌胃给药6周,期间分别对小鼠空腹血糖(FBG)、胰岛素(FIns)和胰岛素抵抗指数(HOMA-IR)进行; 测定比较;并于末次给药后测定各组小鼠葡萄糖耐量(OGTT)和胰岛素耐量(IPITT);通过Western; blot对能量代谢关键蛋白Akt、AMPK和Glut4加以分析。结果表明, N15可显著降低模型小鼠FBG、Fins和HOMA-IR水平(P ; 0.05)。上述结果表明,新型化合物N15具有改善2型糖尿病胰岛素抵抗的功效,其机制可能与增加肝内胰岛素受体调节及促使磷脂酰肌醇3磷酸磷酸化相关; 。This study was designed to investigate the therapeutic effect and; mechanisms of action of novel compound; N-(Z)-9-octadecenyl-2-propanesulfonamide(N15) on type 2 diabetes(T2DM).; A mouse model of T2DM was established with multiple injection of; streptozotocin(STZ) at a low dose. N15 at different doses(50, 100 and; 200 mg·kg~(-1)·d~(-1)) and pioglitazone(6 mg·kg~(-1)·d~(-1)) were; administrated orally for 6 weeks. The level of fasting blood; glucose(FBG) and fasting insulin(FIns) were measured in the course of; the experiment for insulin resistance index(HOMA-IR). Oral glucose; tolerance test(OGTT) and intraperitoneal insulin tolerance test(IPITT); were determined in the treated mice. The expression of Akt, AMPK and; Glut4 in liver were analyzed by Western blot. N15 was found to reduce; the level of FBG, FIns and HOMA-IR(P 0.05). These results suggested that the novel compound; N15 can ameliorate insulin resistance and the potential mechanism may be; associated with increased insulin signaling in liver and promotion of; phosphatidyl inositol 3 phosphate phosphorylation.国家自然基金联合基金; 促进海峡两岸科技合作联合基金项目; 泉州市科技计划项目; 泉州市科技计划项

积雪草苷对高脂血症金黄地鼠脂质调节及肝脏保护作用研究

目的研究积雪草苷对高脂饮食诱导高脂血症模型金黄地鼠血清及肝脏内脂质代谢的影响,探讨其血脂调节功能和肝脏保护作用。方法 60只叙利亚金黄地鼠随机分成6组:正常组,模型组,积雪草苷低剂..

积雪草苷对高脂血症金黄地鼠脂质调节及肝脏保护作用研究

目的 研究积雪草苷对高脂饮食诱导高脂血症模型金黄地鼠血清及肝脏内脂质代谢的影响,探讨其血脂调节功能和肝脏保护作用。方法 60只叙利亚金黄地鼠随机分成6组:正常组,模型组,积雪草苷低剂量(15 mg/kg)、中剂量(30 mg/kg)、高剂量(60 mg/kg)组及血脂康(250 mg/kg)组,每组10只,给予相应药物灌胃,正常组和模型组给予等量溶剂,正常组喂养正常饲料,其余各组喂养高脂饲料。均给予4周。测量各组金黄地鼠血清中的总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷草转氨酶(AST)、谷丙转氨酶(ALT)水平,以及肝脏组织TC、TG、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)水平,选取各组同部位肝脏组织进行冰冻切片,并通过HE染色观察肝脏结构变化。结果 与正常组比较,模型组血清TC、TG、LDL-C、TC/HDL-C、ALT、AST水平以及肝脏TC、TG水平升高(P <0. 05,P<0. 01),肝脏SOD、GSH-PX水平降低(P<0.01)。与模型组比较,各给药组血清TC、TG、LDL-C、TC/HDL-C水平以及肝脏TC、TG水平降低(P<0.01),肝脏SOD、GSH-PX水平升高(P<0.01),血脂康组与积雪草苷低、中剂量组的血清AST水平降低(P<0.01)。肝组织冰冻切片HE染色显示各给药组肝脏脂肪性病变较模型组减轻。结论 积雪草苷可减轻高脂血症模型金黄地鼠的脂肪性病变并缓解肝脏受损程度,其机制可能与增强肝脏抗氧化作用、降低血脂及肝脂有关