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绿原酸通过减轻糖尿病大鼠模型额叶氧化应激和细胞凋亡改善记忆功能障碍。

Chlorogenic acid ameliorates memory dysfunction via attenuating frontal lobe oxidative stress and apoptosis in diabetic rat model.

机构信息

Department of Anatomy, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia.

Master Program on Biomedical Sciences, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia.

出版信息

Turk J Med Sci. 2023 Dec 18;54(4):866-875. doi: 10.55730/1300-0144.5858. eCollection 2024.

Abstract

BACKGROUND/AIM: Diabetes mellitus, characterized by hyperglycemia, causes various complications, one of which is memory dysfunction. The frontal lobe is known to be responsible for impaired memory function due to hyperglycemia and is associated with oxidative stress-mediated neuronal cell apoptosis. Chlorogenic acid (CGA) is reported to have neuroprotective effects. However, its effect on the frontal lobe in diabetes mellitus (DM) rats is not widely known. This research aimed to elucidate the effect of CGA on the mRNA expressions of SOD1, SOD2, p53, and Bcl-2 in the frontal lobe of DM rats.

MATERIALS AND METHODS

Thirty male Wistar rats (2-month-old, 150-200 gBW) were randomly divided into six groups: C (control), DM1.5 (1.5-month DM), DM2 (2-month DM), CGA12.5, CGA25 and CGA50 (DM+CGA 12.5, 25, and 50 mg/kgBW, respectively). A single dose of streptozotocin (60 mg/kgBW) was intraperitoneally injected. Intraperitoneal CGA injection was administered daily for DM1.5 rats for 14 days. Path length was measured in the Morris water maze (MWM) probe test. After termination, the frontal lobes were carefully harvested for RNA extraction. Reverse transcriptase PCR was performed to examine the mRNA expression of SOD1, SOD2, p53, and Bcl-2.

RESULTS

The DM2 group demonstrated significant shorter path length on the MWM probe test and significantly lower mRNA expression of SOD1 and Bcl-2, compared to the C group. After CGA administration, the CGA25 group showed a significantly shorter path length than the C group. The CGA12.5 and CGA25 groups had significantly higher mRNA expression of SOD1 than the DM1.5 group. Compared to the DM1.5 and DM2 groups, SOD2 mRNA expression of the administration of all three CGA doses increased markedly. Furthermore, Bcl-2 mRNA expression was significantly increased in the CGA12.5 and CGA50 groups, compared with the DM2 group.

CONCLUSION

Chlorogenic acid might improve memory function through upregulation of frontal lobes' SOD1, SOD2, and Bcl-2 mRNA expression in DM rats.

摘要

背景/目的:糖尿病(DM)以高血糖为特征,会引起多种并发症,其中之一是记忆功能障碍。已知大脑额叶因高血糖而导致记忆功能受损,与氧化应激介导的神经元细胞凋亡有关。绿原酸(CGA)具有神经保护作用。然而,其在 DM 大鼠额叶中的作用尚不清楚。本研究旨在阐明 CGA 对 DM 大鼠额叶中超氧化物歧化酶 1(SOD1)、SOD2、p53 和 Bcl-2 的 mRNA 表达的影响。

材料和方法

30 只雄性 Wistar 大鼠(2 月龄,150-200 gBW)随机分为六组:C(对照)、DM1.5(1.5 月龄 DM)、DM2(2 月龄 DM)、CGA12.5、CGA25 和 CGA50(DM+CGA 12.5、25 和 50 mg/kgBW)。一次性腹腔内注射链脲佐菌素(60 mg/kgBW)。DM1.5 大鼠每日腹腔注射 CGA,连续 14 天。在 Morris 水迷宫(MWM)探测试验中测量路径长度。试验结束后,小心采集额叶以提取 RNA。逆转录酶 PCR 用于检测 SOD1、SOD2、p53 和 Bcl-2 的 mRNA 表达。

结果

MWM 探测试验中,DM2 组的路径长度明显短于 C 组,SOD1 和 Bcl-2 的 mRNA 表达明显低于 C 组。CGA 给药后,CGA25 组的路径长度明显短于 C 组。与 DM1.5 组相比,CGA12.5 和 CGA25 组 SOD1 的 mRNA 表达明显升高。与 DM1.5 和 DM2 组相比,三种 CGA 剂量给药组的 SOD2 mRNA 表达均显著升高。此外,与 DM2 组相比,CGA12.5 和 CGA50 组的 Bcl-2 mRNA 表达明显增加。

结论

CGA 可能通过上调 DM 大鼠额叶中的 SOD1、SOD2 和 Bcl-2 的 mRNA 表达来改善记忆功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/312e/11407353/2aceddf0afff/tjmed-54-04-866f1.jpg

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