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目的:研究杜仲多糖对链脲佐菌素(STZ)致糖尿病小鼠的作用及影响,并探讨相关机制。方法:取50只SPF级昆明小鼠按剂量120 mg·kg~(-1)ip STZ,ip前禁食12 h。3 d后,测量小鼠空腹血糖(FBG),小鼠FBG≥11.1 mol·L~(-1)表明糖尿病小鼠模型造模成功。将造模成功的小鼠随机分成5组,分别为模型组,二甲双胍组(32 mg·kg~(-1)),杜仲多糖高、中、低剂量组(500,250,125 mg·kg~(-1)),每组10只。另设正常组小鼠10只。连续ig给药14 d,每天1次。正常组和模型组ig给予等体积的生理盐水。末次给药前禁食12 h,给药1 h后拔眼球取血,离心取血清待测。测定14 d小鼠FBG,放射免疫测定法测定小鼠血清中空腹胰岛素(FNS)含量,计算胰岛素敏感指数(ISI),试剂盒测定血清中甘油三酯(TG),总胆固醇(TC),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C)的含量;酶联免疫吸附测定(ELISA)测定血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)和IL-6;蛋白质免疫印迹(Western blot)法测定胰腺组织中转录因子-κB(NF-κB),Toll样受体4(TLR4)的蛋白含量。结果:与正常组比较,模型组小鼠FBG和血脂TG,TC,LDL-C水平明显升高,HDL-C水平,FNS和ISI含量明显降低,血清中TNF-α,IL-8和IL-6含量明显升高,胰腺组织中TLR4,NF-κB蛋白的表达明显升高(P<0.01);与模型组比较,杜仲多糖各剂量组明显降低小鼠FBG和血脂TG,TC,LDL-C水平,明显升高HDL-C水平,FNS和ISI含量,明显降低血清中TNF-α,IL-8和IL-6含量,明显降低胰腺组织中TLR4,NF-κB蛋白的表达(P<0.05,P<0.01)。结论:杜仲多糖具有降血糖和降血脂作用,其作用机制可能与提高糖尿病小鼠机体抗氧化能力、降低炎症因子血清中的含量,以及降低胰腺中TLR4,NF-κB蛋白含量相关。
Objective: To study the effect of eucommia polysaccharide on streptozotocin (STZ) -induced diabetic mice and its mechanism. Methods: 50 SPF Kunming mice were dosed with 120 mg · kg -1 ip STZ for 12 h before ip. After 3 days, the fasting blood glucose (FBG) was measured in mice and FBG≥11.1 mol·L ~ (-1) in mice showed that the model of diabetic mice was successfully established. The mice were randomly divided into 5 groups: model group, metformin group (32 mg · kg -1), eucommia polysaccharides group (500, 250, 125 mg · kg -1) ), 10 in each group. Another set of normal mice 10. Continuous ig administration for 14 days, once daily. Normal group and model group ig given equal volume of saline. Fasting before the last administration of 12 h, 1 h after administration of eyeball bleeding, centrifuged to take serum to be tested. The level of fasting insulin (FNS) in serum was measured by radioimmunoassay (FIA) and the insulin sensitivity index (ISI) was calculated. The serum triglyceride (TG), total cholesterol (TC) (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined by ELISA. Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-8 were measured by enzyme-linked immunosorbent assay (ELISA) (IL-8) and IL-6. Western blot was used to detect the protein levels of NF-κB and Toll-like receptor 4 (TLR4) in pancreatic tissues. Results: Compared with the normal group, the level of FBG, TC, LDL-C and the content of HDL-C, FNS and ISI in the model group were significantly lower than those in the normal group 6, the expression of TLR4 and NF-κB in pancreatic tissue was significantly increased (P <0.01). Compared with the model group, each dose of Eucommia ulmoides polysaccharide significantly reduced FBG and TG, TC, LDL-C (P <0.05). The levels of HDL-C, FNS and ISI were significantly increased, and the levels of TNF-α, IL-8 and IL-6 in serum were significantly decreased P <0.01). Conclusion: The polysaccharides of Eucommia ulmoides have hypoglycemic and hypolipidemic effects. The mechanism may be related to the antioxidation, the decrease of inflammatory cytokines and the decrease of TLR4 and NF-κB in the pancreas of diabetic mice.