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荔枝核有效部位群改善实验性2型糖尿病胰岛素抵抗的作用及机制 被引量:12

Effect and Mechanism of Litchi Semen Effective Constituents on Insulin Resistance in Rats with Type 2 Diabetes Mellitus
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摘要 目的:研究荔枝核有效部位群(含总皂苷、黄酮和鞣质)改善2型糖尿病胰岛素抵抗的作用及机制。方法:建立高脂饮食加链脲佐菌素诱导2型糖尿病大鼠动物模型,随机分为模型组、荔枝核有效部位群高剂量组(1.87 g/kg)、荔枝核有效部位群低剂量组(0.47 g/kg)及盐酸罗格列酮组(3.87×10-3g/kg),另设正常对照组,给药4 w,观察荔枝核有效部位群对实验大鼠糖脂代谢、胰岛素抵抗和胰组织病理改变及超微结构的影响,检测各组大鼠胰组织GRP78、CHOP mRNA表达变化。结果:荔枝核有效部位群高剂量可降低大鼠空腹血糖(FBG)和血清甘油三酯(TG)水平并提高口服糖耐量(P<0.05或P<0.01);荔枝核有效部位群高、低剂量能显著提高胰岛素敏感指数(ISI),降低稳态胰岛素抵抗指数(HOMA-IR)(P<0.05或P<0.01),明显改善大鼠胰腺组织的病理损伤,并促进内质网、线粒体等损伤细胞器的修复;与模型组比较,荔枝核有效部位群高、低剂量组胰腺组织GRP78 mRNA及高剂量组CHOP mRNA表达水平均显著降低(P<0.01)。结论:荔枝核有效部位群具有改善糖脂代谢、提高胰岛素敏感性、改善胰岛素抵抗和治疗2型糖尿病作用,其机制与抑制胰组织内质网应激关键基因GRP78及CHOP的mRNA表达有关。 Objective: To observe the effect of Litchi Semen Effective Constituents( LSEC) on insulin resistance( IR) in rats with Type 2 Diabetes Mellitus( T2DM),and to explore its mechanism. Method: T2 DM models in rats with IR were induced by high-fat feeding combined with streptozocin,then the rats were randomly divided into four groups: model group,LSEC high-dose group( 1. 87 g / kg),LSEC low-dose group( 0. 47 g / kg) and rosiglitazone group( 3. 87 × 10- 3g / kg),blank group was established as control. After medication for four weeks,effects of LSEC on glucose or lipid metabolism and insulin resistance were investigated,histopathology and ultrastructure changes of pancreatic tissues were observed,Stem-loop Real-time fluorescence quantitative RT-PCR was used for evaluation of GRP78 mRNA and CHOP mRNA levels in pancreatic tissue of rats. Result: LSEC of high-dose group obviously improved fasting blood glucose,serum TG level and glucose tolerance in T2 DM rats( P〈 0. 05 or P〈 0. 01). ISI was increased,HOMA-IR index was decreased,histopathology change of pancreatic tissue were alleviated,damaged organelle,such as endoplasmic reticulum and mitochondria were repaired in both groups of LSEC. Expression levels of GRP78 mRNA of both groups of LSEC and CHOP mRNA of high-dose group in pancreatic tissue were obviously lower than those of model group( P〈 0. 01). Conclusion: LSEC can improve glycolipid metabolism and IR,increase insulin sensitivity to cure T2 DM,its effects may be attributed,at least in part,to inhibit the expression of GRP78 mRNA and CHOP mRNA.
出处 《中药材》 CAS CSCD 北大核心 2015年第7期1466-1471,共6页 Journal of Chinese Medicinal Materials
基金 广东省重大科技专项(2012A080202010) 广东省自然科学基金(S2013010012998) 广州市科技计划应用研究基础专项(2013J4100088) 广东省中医药局基金(20122004)
关键词 荔枝核有效部位群 2型糖尿病 胰岛素抵抗 内质网 线粒体 葡萄糖调节蛋白78 CCAAT/增强子结合蛋白同源蛋 Litchi Semen Effective Constituents Type 2 Diabetes Mellitus Insulin resistance Endoplasmic reticulum Mitochondria GRP78 CHOP
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