丹红注射液对糖尿病合并脑缺血大鼠的神经保护作用及Nrf2/HO-1通路的影响

Effects of Danhong Injection on Neuroprotective Effect and Nrf2/HO-1 Pathway in Diabetic Rats with Cerebral Ischemia

目的观察丹红注射液对糖尿病合并脑缺血大鼠的神经保护作用及转录因子红细胞2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)通路的影响。方法 SD大鼠100只,分成5组:对照组、模型组及丹红注射液低、中、高剂量组。模型组、丹红注射液各剂量组构建糖尿病合并脑缺血大鼠模型,并于造模成功开始给予相应药物灌胃,对照组和模型组给予等体积0.9%氯化钠注射液。实验结束后,对大鼠进行神经缺失神经细胞症状评分、计算神经细胞存活率;检测大鼠脊髓组织中Nrf2、HO-1 mRNA、蛋白水平以及丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)蛋白表达水平。结果与对照组比较,丹红注射液各剂量组神经缺失症状评分升高,神经细胞存活率降低(P <0.05);与模型组比较,丹红注射液各剂量神经缺失症状评分降低(P <0.05),神经细胞存活率升高(P <0.05)。与对照组比较,模型组、丹红注射液低、中剂量组脊髓组织Nrf2、HO-1 mRNA、蛋白表达水平及MDA、NO蛋白表达水平明显升高,SOD蛋白表达水平明显降低(P <0.05);与模型组比较,丹红注射液各剂量组Nrf2、HO-1 mRNA、蛋白表达水平及MDA、NO蛋白表达水平明显降低,SOD蛋白表达水平明显升高(P <0.05)。结论丹红注射液能显著改善糖尿病合并脑缺血大鼠引起的神经缺失症状,减轻脊髓神经元损伤程度,其机制与抑制Nrf2、HO-1 mRNA、蛋白的表达水平,激活抗氧化途径,降低氧化应激产物水平有关。

Objective:To investigate the neuroprotective effect of Danhong Injection on diabetic rats with cerebral ischemia and the effect on Nrf2/HO-1 pathway. Methods:100 SD rats were randomly divided into 5 groups:the control group,the model group,low,medium and high dose Danhong Injection groups. Rat models of diabetes mellitus combined with cerebral ischemia were established in the model group and Danhong Injection groups,and the corresponding drugs were given by gastric perfusion at the beginning of successful modeling. The control group and the model group were given equal volume of saline. After experiment,the symptoms of nerve-deficient neurons were scored and survival rate of nerve cells was calculated. The expression of Nrf2,HO-1,protein and MDA,NO and SOD protein in spinal cord tissue were detected. Results:Compared with the control group,the scores of neurological deficit symptoms increased and the survival rate of neurons decreased in Danhong Injection groups(P < 0.05). Compared with the model group,the scores of neurological deficit symptoms in Danhong Injectiongroups decreased(P < 0.05),and the survival rate of neurons increased(P < 0.05). Compared with the control group,the expression levels of Nrf2,HO-1,MDA,NO and SOD in spinal cord tissue of the model group,Danhong Injection low and middle dose groups were significantly higher,while the expression levels of SOD were significantly lower(P < 0.05). Compared with the model group,the levels of Nrf2,HO-1,protein expression,MDA,NO protein expression decreased and SOD protein expression increased significantly in Danhong Injection groups(P <0.05). Conclusion:Danhong Injection significantly reduced the neurological deficit symptoms caused by diabetes mellitus combined with cerebral ischemia in rats,and alleviated the degree of spinal cord neuron injury. Its mechanism is related to inhibiting the mRNA protein expression of Nrf2 and HO-1,activating the antioxidant pathway and reducing the level of oxidative stress products.