浙江中西医结合杂志

陈新新,张世正,黄小亚,黄建平.奇壬醇通过激活Nrf-2/HO-1信号通路减轻大脑缺血再灌注损伤[J].浙江中西医结合杂志,2026,36(6):

奇壬醇通过激活Nrf-2/HO-1信号通路减轻大脑缺血再灌注损伤

Kirenol activates Nrf-2/HO-1 signaling pathway-mediated antioxidant action to attenuate ischemia-reperfusion injuryCHEN Xinxin ZHANG Shizheng HUANG Xiaoya HUANG Jianping

投稿时间：2025-11-30 修订日期：2026-04-22

DOI：

中文关键词: 奇壬醇脑缺血/再灌注损伤氧化应激抗氧化 Nrf-2/HO-1通路

英文关键词:Kirenol, cerebral ischemia-reperfusion injury, oxidative stress, antioxidant, Nrf2/HO-1 pathway

基金项目:温州市科研项目(Y2023843)浙江；浙江省医药卫生科技计划项目(2024KY1624)

作者	单位	E-mail
陈新新^*	温州市中心医院（原上海大学第二人民医院）	378237687@qq.com
张世正	温州市中心医院
黄小亚	温州市中心医院
黄建平	温州市中心医院

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中文摘要:

摘要:目的探讨奇壬醇(KRL)通过激活Nrf2/ HO-1信号通路抑制氧化应激反应，减轻大脑缺血再灌注损伤。方法采用大鼠脑梗死缺血/再灌注（MACO）动物模型，分为假手术组、对照组（MACO模型）、实验组（MACO模型+注射奇任醇）。我们通过神经功能量表、TTC染色评估大鼠脑缺血/再灌注损伤的程度；使用尼氏染色（Nissl）和Tunel染色分别评估大鼠大脑皮层和海马的神经元细胞形态和凋亡情况；通过免疫组化检测氧化应激反应的关键标志物，包括8-羟基脱氧鸟苷（8-OHdG）和诱导型一氧化氮合酶（iNos）；检测了大鼠脑组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的活性以评估氧化损伤的程度。此外，使用免疫荧光染色、逆转录聚合酶链反应（RT-PCR）和免疫蛋白印记分析，检查Nrf-2和HO-1信号通路的表达水平。结果实验结果发现：与对照组比较，实验组大鼠神经功能评分明显降[（0.20±0.45）分比（2.40±0.55）分，P＜0.001]；实验组脑梗死面积比例显著减少[（8.14±2.65）%比（43.44±1.84）%，P＜0.001]；实验组染色显示神经元完整细胞数更多，Nissl [皮层：（81.40±9.53）个比（4.60±1.67）个，P＜0.001。海马：（50.00±6.29）个比（3.40±1.14）个，P＜0.001]；Tunel[皮层：（15.02±1.76）%比（36.73±1.55）%，P＜0.001。海马：（13.88±1.62）%比（33.12±2.75）%，P＜0.001]；实验组明显抑制氧化应激反应，8-OHdG[皮层：（14.90±1.90）%比（35.54±3.84）%，P＜0.001。海马：（15.25±2.23）%比（30.11±2.78）%，P＜0.001]、iNos[皮层：（13.70±1.61）% 比（36.59±3.73）%，P＜0.001。海马：（15.00±2.24）%比（34.13±3.54）%，P＜0.001]、MDA[皮层：（1.55±0.14）nmol/mgprot比（2.98±0.09）nmol/mgprot，P＜0.001。海马：（1.42±0.04）nmol/mgprot比（2.37±0.02）nmol/mgprot，P＜0.001]水平明显降低；SOD[皮层：（218.00±5.12）U/mgprot比（140.80±10.75）U/mgprot，P＜0.001。海马：（377.69±5.22）比）280.39±15.71），P＜0.001]活性增加；免疫荧光显示实验组Nrf-2[皮层：（29.86±4.85）%比（16.47±2.30）%，P＜0.001）]、HO-1（皮层：（39.86±4.14）% 比（6.25±2.35）%，P＜0.001）]的阳性率明显增加；Western blot法检测显示实验组Nrf-2[皮层：（2.54±0.20）比（1.77±0.40），P＜0.001。海马：（2.21±0.19）比（1.66±0.10），P＜0.001]、HO-1[皮层：（2.88±0.16）比（2.04±0.15），P＜0.001。海马：（2.56±0.25）比（1.76±0.17），P＜0.001]的表达水平显著增加；RT-PCR检测显示实验组Nrf-2[皮层：（12.12±1.39）比（4.88±0.69），P＜0.001。海马：（8.42±0.74）比（5.60±0.99），P＜0.001]、HO-1[皮层：（10.11±1.75）比（5.29±0.87），P＜0.001。海马：（11.62±1.20）比（5.01±1.26），P＜0.001]的基因表达水平显著增加。结论奇任醇通过调节Nrf-2/HO-1信号通路减轻脑缺血/再灌注损伤，为开发新型抗氧化剂治疗缺血性脑卒中提供了实验依据。

英文摘要:

Objective To explore the neuroprotective effects of Kirenol in alleviating cerebral ischemia-reperfusion injury through the activation of the Nrf2/HO-1 signaling pathway, and its potential in inhibiting oxidative stress. Methods A rat model of middle cerebral artery occlusion (MCAO) was used, with groups including sham-operated, control (MCAO), and experimental (MCAO + Kirenol). Neurological deficit and TTC was used to asses the degree of cerebral ischemia/reperfusion injury in rats. Nissl and Tunel staining were used to evaluate neuronal morphology and apoptosis in the cortex and hippocampus in rats. Key oxidative stress markers, including 8-OHdG and iNOS, were measured by immunohistochemistry. And the activities of SOD and MDA were quantified to assess oxidative damage. Furthermore, expression levels of Nrf2 and HO-1 were analyzed using immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Results The experimental results showed that compared to the control group, the experimental group of rats had a significantly lower neurological function score [(0.20±0.45) points vs. (2.40±0.55) points, P<0.001]; the proportion of cerebral infarction area was significantly reduced [(8.14±2.65)% vs. (43.44±1.84)%, P<0.001]; The number of intact neurons has increased [cortex: (81.40±9.53) cells vs. (4.60±1.67) cells, P<0.001; hippocampus: (50.00±6.29) cells vs. (3.40±1.14) cells, P<0.001]; Significant reduction in apoptosis of brain cells [cortex: (15.02±1.76)% vs. (36.73±1.55)%, P<0.001; hippocampus: (13.88±1.62)% vs. (33.12±2.75)%, P<0.001]; 8-OHdG [cortex: (14.90±1.90)% vs. (35.54±3.84)%, P<0.001; hippocampus: (15.25±2.23)% vs. (30.11±2.78)%, P<0.001], iNOS [cortex: (13.70±1.61)% vs. (36.59±3.73)%, P<0.001; hippocampus: (15.00±2.24)% vs. (34.13±3.54)%, P<0.001], and MDA [cortex: (1.55±0.14) nmol/mg prot vs. (2.98±0.09) nmol/mg prot, P<0.001; hippocampus: (1.42±0.04) nmol/mg prot vs. (2.37±0.02) nmol/mg prot, P<0.001] levels significantly decreased; SOD [cortex: (218.00±5.12) U/mg prot vs. (140.80±10.75) U/mg prot, P<0.001; hippocampus: (377.69±5.22) vs. (280.39±15.71), P<0.001] activity increased; immunofluorescence showed a significant increase in the positive rates of Nrf-2 [cortex: (29.86±4.85)% vs. (16.47±2.30)%, P<0.001] and HO-1 [cortex: (39.86±4.14)% vs. (6.25±2.35)%, P<0.001] in the experimental group; Western blot analysis indicated that the expression levels of Nrf-2 [cortex: (2.54±0.20) vs. (1.77±0.40), P<0.001; hippocampus: (2.21±0.19) vs. (1.66±0.10), P<0.001] and HO-1 [cortex: (2.88±0.16) vs. (2.04±0.15), P<0.001; hippocampus: (2.56±0.25) vs. (1.76±0.17), P<0.001] were significantly increased; RT-PCR showed that the gene expression levels of Nrf-2 [cortex: (12.12±1.39) vs. (4.88±0.69), P<0.001; hippocampus: (8.42±0.74) vs. (5.60±0.99), P<0.001] and HO-1 [cortex: (10.11±1.75) vs. (5.29±0.87), P<0.001; hippocampus: (11.62±1.20) vs. (5.01±1.26), P<0.001] were significantly increased. Conclusion Kirenol mitigates cerebral ischemia-reperfusion injury by activating the Nrf2/HO-1 pathway, providing experimental support for the development of novel antioxidant therapies for ischemic stroke.

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