| 黄 河,杜泓森,李继科,寇 进,权青云,刘 佳,关 芳.黄腐酚对高脂饮食大鼠心肌缺血再灌注后的认知功能障碍的改善作用[J].,2024,(21):4020-4027 |
| 黄腐酚对高脂饮食大鼠心肌缺血再灌注后的认知功能障碍的改善作用 |
| Effect of Xanthohumol on Cognitive Impairment after Myocardial Ischemia-reperfusion in Rats with High-fat Diet |
| 投稿时间：2024-04-01 修订日期：2024-05-12 |
| DOI：10.13241/j.cnki.pmb.2024.21.004 |
| 中文关键词: 黄腐酚 高脂饮食 心肌缺血再灌注损伤 认知功能障碍 细胞凋亡 抗氧化 抗炎 淀粉样蛋白 |
| 英文关键词: Xanthohumol High-fat diet Myocardial ischemia-reperfusion injury Cognitive impairment Apoptosis Antioxidation Anti-inflammation Amyloid protein |
| 基金项目:陕西省自然科学基础研究计划项目（2022JQ-844） |
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| 中文摘要: |
| 摘要 目的：探讨黄腐酚（XN）对高脂饮食（HFD）大鼠心肌缺血再灌注后认知功能障碍的改善作用。方法：建立HFD+心肌缺血再灌注损伤（MIRI）大鼠模型后，将大鼠分为Sham组、HFD+MIRI组、HFD+MIRI+L-XN组、HFD+MIRI+M-XN组和HFD+MIRI+H-XN组。Sham组和HFD+MIRI组大鼠灌胃0.5% CMC-Na，HFD+MIRI+L-XN组、HFD+MIRI+M-XN组和HFD+MIRI+H-XN组大鼠分别灌胃30、60和120 mg/kg/d的XN，连续给药8周。采用Morris水迷宫实验评估认知功能。采用试剂盒检测大鼠血清脂代谢和心肌损伤指标以及心肌和脑组织氧化应激和炎症指标，并对大鼠心肌和脑组织进行HE和TUNEL染色。采用RT-qPCR检测Bax和Bcl2 mRNA。采用Western blot检测Bax、Bcl2、BACE1、Aβ1-42、p-NF-κB p65和Nrf2蛋白。结果：与Sham组比较，HFD+MIRI组大鼠的逃避潜伏期增加（P<0.05），60 s内经过站台的次数减少（P<0.05）；血清TC、TG、LDL-c、FFA、CK-MB、LDH和cTnI水平升高（P<0.05），HDL-c水平降低（P<0.05）；心肌和脑组织中TUNEL阳性率以及MDA、TNF-α、IL-1β和IL-6水平均升高（P<0.05），心肌和脑组织中SOD、GSH-Px和CAT水平均降低（P<0.05）；脑组织中BACE1和Aβ1-42蛋白相对表达量升高（P<0.05），心肌和脑组织中Bax和p-NF-κB p65蛋白相对表达量升高（P<0.05），Bcl2和细胞核Nrf2蛋白相对表达量降低（P<0.05）。与HFD+MIRI组比较，HFD+MIRI+L-XN组、HFD+MIRI+M-XN组和HFD+MIRI+H-XN组大鼠的逃避潜伏期减少（P<0.05），60 s内经过站台的次数增加（P<0.05）；血清TC、TG、LDL-c、FFA、CK-MB、LDH和cTnI水平降低（P<0.05），HDL-c水平升高（P<0.05）；心肌和脑组织中TUNEL阳性率以及MDA、TNF-α、IL-1β和IL-6水平均降低（P<0.05），心肌和脑组织中SOD、GSH-Px和CAT水平均升高（P<0.05）；脑组织中BACE1和Aβ1-42蛋白相对表达量降低（P<0.05），心肌和脑组织中Bax和p-NF-κB p65蛋白相对表达量降低（P<0.05），Bcl2和细胞核Nrf2蛋白相对表达量升高（P<0.05）。结论：XN对HFD大鼠MIRI后的认知功能障碍有改善作用，其机制涉及抗凋亡、抗氧化、抗炎和抑制A?茁的形成。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of xanthohumol (XN) on cognitive impairment after myocardial ischemia-reperfusion in rats with high-fat diet (HFD). Methods: After establishing the rat model of HFD+myocardial ischemia-reperfusion injury (MIRI), rats were divided into Sham group, HFD+MIRI group, HFD+MIRI+L-XN group, HFD+MIRI+M-XN group and HFD+MIRI+H-XN group. Rats in Sham group and HFD+MIRI group were given 0.5% CMC-Na, and rats in HFD+MIRI+L-XN group, HFD+MIRI+M-XN group and HFD+MIRI+H-XN group were given 30, 60 and 120 mg/kg/d XN, respectively. The drug was administered continuously for 8 weeks. The Morris water maze test was used to evaluate cognitive function. Serum lipid metabolism and myocardial damage indexes, oxidative stress and inflammation indexes of myocardial and brain tissues were detected according to the kit instructions, and the myocardial and brain tissues were stained by HE and TUNEL. Bax and Bcl2 mRNA were detected by RT-qPCR. BACE1, Aβ1-42, p-NF-κB p65 and Nrf2 proteins were detected by Western blot. Results: Compared with Sham group, the escape latency of HFD+MIRI group increased (P<0.05), the number of times passing through the platform decreased within 60 s decreased (P<0.05), the levels of TC, TG, LDL-c, FFA, CK-MB, LDH and cTnI all increased (P<0.05), the level of HDL-c decreased (P<0.05), the positive rate of TUNEL and the level of MDA, TNF-α, IL-1β and IL-6 in myocardium and brain increased (P<0.05), the levels of SOD, GSH-Px and CAT in myocardium and brain decreased (P<0.05), the relative expression of BACE1 and Aβ1-42 protein in brain tissue increased (P<0.05), the relative expression of Bax and p-NF-κB p65 protein in myocardial and brain tissue increased (P<0.05), and the relative expression of Bcl2 and nuclear Nrf2 protein decreased (P<0.05). Compared with HFD+MIRI group, the escape latency of HFD+MIRI+L-XN group, HFD+MIRI+M-XN group and HFD+MIRI+H-XN group decreased (P<0.05), the number of times passing through the platform decreased within 60 s increased (P<0.05), the levels of TC, TG, LDL-c, FFA, CK-MB, LDH and cTnI all decreased (P<0.05), the level of HDL-c increased (P<0.05), the positive rate of TUNEL and the level of MDA, TNF-α, IL-1β and IL-6 in myocardium and brain decreased (P<0.05), the levels of SOD, GSH-Px and CAT in myocardium and brain increased (P<0.05), the relative expression of BACE1 and Aβ1-42 protein in brain tissue decreased (P<0.05), the relative expression of Bax and p-NF-κB p65 protein in myocardial and brain tissue decreased (P<0.05), and the relative expression of Bcl2 and nuclear Nrf2 protein increased (P<0.05). Conclusion: XN improves cognitive dysfunction in HFD rats after MIRI, and its mechanism involves anti-apoptosis, anti-oxidation anti-inflammation, and inhibition of Aβ formation. |
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