鱼油通过影响脂质合成增强二甲双胍对2型糖尿病大鼠的作用研究

Fish oil enhancing the effect of metformin on type 2 diabetic rats by affecting lipid synthesis

目的研究鱼油与二甲双胍联用在预防治疗2型糖尿病大鼠中的作用。方法用高脂高糖饲料和一次性腹腔注射链脲佐菌素40 mg·kg-1的方法建立2型糖尿病大鼠模型。按照体重将大鼠分为5组:正常组、模型组、二甲双胍组、鱼油组和联合组,每组15只。正常组和模型组给予0.9%Na Cl灌胃;于造模第8周开始,二甲双胍组给予二甲双胍200 mg·kg-1,连续给药8周;于造模前1周,鱼油组开始灌胃鱼油670 mg·kg-1,直至实验结束;联合组同时给予相同剂量的二甲双胍和鱼油。用酶联免疫吸附法测定血清中血清总胆固醇(TC)和肿瘤坏死因子-α(TNF-α)水平,用蛋白质印迹法检测蛋白磷酸化信号传导及转录激活因子3(P-stat3)的表达水平。结果正常组、模型组、二甲双胍组、鱼油组和联合组的TC水平分别为(3.58±1.26),(6.78±3.23),(5.08±1.35),(4.12±1.44)和(3.23±1.02)mmol·L-1;上述这5组TNF-α的含量分别为(2.77±0.96),(4.97±0.51),(4.77±0.45),(3.57±0.40)和(2.73±0.57)mmol·L-1;上述这5组P-stat3蛋白表达水平(OD值)分别为0.45±0.12,0.87±0.16,0.74±0.15,0.56±0.11和0.32±0.10。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.05);鱼油组和联合组与模型组比较,差异均有统计学意义(均P<0.05)。结论二甲双胍与鱼油联用能显著增强二甲双胍的疗效,这可能与鱼油能够调节2型糖尿病脂质代谢紊乱,特别是影响脂质合成有关,还可能跟鱼油影响Stat3通路抑制炎症相关。

Objective To explore the role of fish oil combined with metformin in the prevention and treatment of type 2 diabetic rats.Methods A rat model of type 2 diabetes was established by high-fat diet and a single intraperitoneal injection of streptozotocin 40 mg·kg-1.The rats were divided into five groups:normal group,model group,metformin group,fish oil group and combination group(n=15 in each group).Rats in normal group and model group were orally administered with 0.9%saline.Beginning from the 8th week of modeling,rats in metformin group were orally treated with metformin(200 mg·kg-1)for8 weeks.Before modeling,rats in fish oil group were orally administered with fish oil(200 mg·kg-1)until the end of the experiment.The combination group was given the same dose of metformin and fish oil.The serum total cholesterol(TC)and tumor necrosis factor-α(TNF-α)levelswere determined by enzyme-linked immunosorbent assay.The expression of phosphorylation signaling and activatortranscription 3(P-stat3)was determined by Western blotting.Results The levels of TC in normal group,mogroup,metformin group,fish oil group,and combination group were(3.58±1.26),(6.78±3.23(5.08±1.35),(4.12±1.44),and(3.23±1.02)mmol·L-1,respectively;the contents of TNF-αin the ab5 groups were(2.77±0.96),(4.97±0.51),(4.77±0.45),(3.57±0.40),(2.73±0.57)mmol·Lrespectively;the expression level(OD value)of P-stat3 proteins in the above 5 groups were 0.45±0.10.87±0.16,0.74±0.15,0.56±0.11,and 0.32±0.10,respectively.Comparing between model group and norgroup,the difference of the factors were significant(all P<0.01);comparing between fish oil group or combinatgroupand model group,the difference of the factors were significant(P<0.01).Conclusion The combinationmetformin and fish oil can significantly enhance the efficacy of metformin,which may be owing to fish oil regulating lipid metabolism disorder of type 2 diabetes,especially affecting lipid synthesis,as well as affecting the stat3 pathwto inhibit inflammation.