杜仲木脂素对糖尿病脑病大鼠的治疗作用及机制研究

Therapeutic effect and mechanism of Eucommia lignans on diabetes encephalopathy rats

目的探讨杜仲木脂素对糖尿病脑病(DE)大鼠的治疗作用及核因子E2相关因子2(Nrf2)/血红素氧化酶1(HO-1)信号通路的影响。方法构建DE大鼠模型,将建模成功的48只大鼠随机分为模型组、杜仲木脂素低剂量组(200mg/kg)、杜仲木脂素高剂量组(400mg/kg)、二甲双胍组(200mg/kg),每组12只。另选取12只健康大鼠作为对照组。各组每天给予相应药物干预1次,连续6周。检测大鼠认知和记忆能力、血清白细胞介素6(IL-6)、TNF-α、丙二醛、超氧化物歧化酶(SOD)、脑组织海马区中Nrf2、HO-1信使RNA(mRNA)和蛋白表达水平;并观察脑组织海马区病理学变化。结果与对照组比较,模型组大鼠逃避潜伏期、血清IL-6、TNF-α、丙二醛水平显著升高,经过原平台位置次数、原平台象限停留时间、血清SOD水平、脑组织海马区中Nrf2、HO-1mRNA和蛋白表达水平显著降低(P<0.05);与模型组比较,杜仲木脂素低、高剂量组大鼠逃避潜伏期、血清IL-6、TNF-α、丙二醛水平显著降低,经过原平台位置次数、原平台象限停留时间、血清SOD水平、脑组织海马区中Nrf2、HO-1mRNA和蛋白表达水平显著升高(P<0.05)。与杜仲木脂素低剂量组比较,杜仲木脂素高剂量组大鼠逃避潜伏期、血清IL-6、TNF-α、丙二醛水平显著降低(P<0.05);杜仲木脂素高剂量组经过原平台位置次数、原平台象限停留时间、血清SOD水平、脑组织海马区中Nrf2、HO-1mRNA表达水平显著高于杜仲木脂素低剂量组[(6.07±0.70)次vs(4.76±0.52)次、(30.96±2.96)svs(23.49±2.60)s、(77.02±6.51)U/mlvs(61.71±6.75)U/ml、(0.69±0.06)vs(0.49±0.05)、(0.74±0.07)vs(0.57±0.06),P<0.05]。结论杜仲木脂素能改善DE大鼠认知能力,提升其抗氧化能力并抑制炎性反应,保护大鼠脑组织海马区,其机制可能与激活Nrf2/HO-1信号通路有关。

Objective To explore the therapeutic effect of lignans extracted from Eucommia Ulmoides Oliver on diabetes encephalopathy(DE)rats and the effects on nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods A rat model of DE was established,and 48 successfully established DE rats were randomly divided into model group,and low-and high-dose lignans groups(200 and 400 mg/kg),and metformin(200 mg/kg)group,with 12 rats in each group.Another 12 healthy rats served as control group.Each group of rats was given corresponding drug intervention once a day for 6 consecutive weeks.Cognitive and memory abilities,serum levels of 1L-6,TNF-a,MDA and SOD,and mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were measured in all groups.Pathological changes of the hippocampus were observed after HE staining.Results Compared with the control group,significantly longer escape latency and increased serum levels of 1L-6,TNF-a and MDA,while lower times of crossing original platform,shorter residence duration of original platform quadrant,decreased serum SOD level,and reduced mRNA and protein levels of Nrf2 and HO-1 in the hippocampus were observed in the model group(all P<0.05).Low-and high-dose lignans treatment reversed all above indica-tors when compared with model group(P<0.05).What’s more,the effects of high-dose lignans treatment were more significant than low-dose treatment in escape latency,serum levels of IL-6,TNF-a and MDA,times through the original platform,residence duration of the original platform quadrant,serum SOD level,and mRNA Nrf2 and HO-1 in the hippocampus(6.07±0.70 us 4.76±0.52,30.96±2.96 s us 23.49±2.60 s,77.02±6.51 U/ml us 61.71±6.75 U/ml,0.69±0.06 us 0.49±0.05,0.74±0.07 us 0.57±0.06,P<0.05).Conclusion Eucommia lignans can improve the cogni-tive ability,enhance the antioxidant capacity,inhibit inflammatory response and protect the hippo-campus of DE rats,and the mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.