肌肽对糖尿病大鼠海马中氧化应激及NF-&kappa;B信号通路的影响

赵丹婷; 刘影; 赵艳; 鲁美丽; 杨文强; 何鑫; 杨菁

doi:10.13418/j.issn.1001-165x.2018.05.007

中国临床解剖学杂志 ›› 2018, Vol. 36 ›› Issue (5) : 514-519. DOI: 10.13418/j.issn.1001-165x.2018.05.007

实验研究

肌肽对糖尿病大鼠海马中氧化应激及NF-κB信号通路的影响

赵丹婷，　刘影，　赵艳，　鲁美丽，　杨文强，　何鑫，　杨菁

作者信息 +

Effect of Carnosine on oxidative stress and NF-κB signaling pathway in hippocampus of diabetic rats

ZHAO Dan-ting, LIU Ying, ZHAO Yan, LU Mei-li, YANG Wen-qiang, HE Xin，YANG Jing

Author information +

文章历史 +

摘要

目的　探讨肌肽（Carnosine, CAR）对糖尿病大鼠认知功能及大鼠海马中氧化应激和NF-κB信号通路的影响。方法　50只雄性SD大鼠，除外对照组（n=8）均给予高糖高脂饲料，腹腔注射STZ建立Ⅱ型糖尿病模型，随机分为糖尿病模型组和不同剂量的肌肽组（100、300和900 mg/kg）。给药56 d后，Morris水迷宫进行行为学测试；HE染色观察海马病理变化；应用试剂盒法检测海马中的超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量；高效液相色谱法（HPLC）检测海马中谷胱甘肽（GSH）、肌肽的含量；Western Blot检测胞浆中TNF-α、IL-1β，胞核中NF-κB p65的表达。结果　与糖尿病组相比，肌肽组可以明显改善糖尿病大鼠的学习记忆能力和海马神经细胞形态，提高糖尿病大鼠海马中SOD活性及GSH、肌肽的含量，降低MDA的含量，同时肌肽可以明显降低糖尿病大鼠海马胞核中NF-κB蛋白向核内转移，并下调下游炎症因子TNF-α、IL-1β蛋白的表达。结论　肌肽改善糖尿病大鼠的认知功能障碍，其机制可能是通过抑制氧化应激反应，并减少NF-κB向核内转移、下调TNF-α、IL-1β的表达有关。

Abstract

Objective To investigate the effect of Carnosine (CAR) on cognitive function and oxidative stress and NF-κB signaling pathway in diabetic rats. Methods Fifty male SD rats, except the normal group (n=8), were given high fat and sugar diet, and intraperitioneal injection of STZ to establish type Ⅱ diabetes rats. The rats were randomly divided into the diabetic model group and Carnosine groups with different doses (100, 300 and 900 mg/kg). All drugs were administrated for 56 days. The behavior tests were performed on the Morris water maze method. HE stain were used to observe the pathological changes of the hippocampus. The activity of SOD and the content of MDA in the hippocampus were detected by respective commercial kits. The content of GSH and carnosine in hippocampus tissue were detected by HPLC. Western Blot were used to detect the expression of TNF-α, IL-1β in cytoplasm and NF-κB p65 in nucleus. Results Compared with diabetic group, Carnosine groups improved significantly learning and memory ability and the morphology of hippocampal neuronal cell in diabetic rats, enhanced the activity of SOD, the content of GSH and carnosine in the hippocampus of diabetic rats, inhibited the content of MDA, which, at the same time, reduced significantly the nuclear transfer of NF-κB with the nucleus of hippocampus in diabetic rats and down-regulated the expression of downstream inflammatory cytokines TNF-α and IL-1β. Conclusion Carnosine may prevent cognitive dysfunction in DM rats. The mechanism may be in connection with its function that it can inhibit oxidative stress, reduce NF-κB translocating into the nucleus and the expression of TNF-α and IL-1β.

导出引用

赵丹婷,刘影,赵艳,鲁美丽,杨文强,何鑫,杨菁. 肌肽对糖尿病大鼠海马中氧化应激及NF-κB信号通路的影响[J]. 中国临床解剖学杂志. 2018, 36(5): 514-519 https://doi.org/10.13418/j.issn.1001-165x.2018.05.007

ZHAO Dan-ting, LIU Ying, ZHAO Yan, LU Mei-li, YANG Wen-qiang, HE Xin，YANG Jing. Effect of Carnosine on oxidative stress and NF-κB signaling pathway in hippocampus of diabetic rats[J]. Chinese Journal of Clinical Anatomy. 2018, 36(5): 514-519 https://doi.org/10.13418/j.issn.1001-165x.2018.05.007

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