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替莫唑胺可改善实验性蛛网膜下腔出血后继发的迟发性脑损伤和脑血管痉挛。

Thymoquinone ameliorates delayed cerebral injury and cerebral vasospasm secondary to experimental subarachnoid haemorrhage.

机构信息

Neurosurgery Department of Şişli Hamidiye Etfal Training and Research Hospital, İstanbul /Turkey, İstanbul, Turkey.

Department of Neurosurgery, Haseki Training and Research Hospital, Istanbul.

出版信息

Neurol Neurochir Pol. 2020;54(6):576-584. doi: 10.5603/PJNNS.a2020.0090. Epub 2020 Nov 30.

Abstract

AIM OF THE STUDY

Among subarachnoid haemorrhage (SAH) patients, delayed cerebral injury (DCI) and infarction are the most important causes of death and major disability. Cerebral vasospasm (cVS) and DCI remain the major cause of death and disability. Thymoquinone (TQ) is the substance most responsible for the biological activity of nigella sativa (NS) and is useful in the treatment of ischaemic and neurodegenerative diseases, oxidative stress, inflammatory events, cardiovascular and neurological diseases. We conducted an experimental study aimed to investigate the preventive and corrective effects of TQ.

MATERIALS AND METHODS

24 Sprague-Dawley rats were randomly divided into three groups. The first was the control group which was a sham surgery group. The second group was the SAH group where the double haemorrage SAH protocol was used to induce vasospasm. The third group was the SAH+TQ group, where cVS was induced by the SAH protocol and the animals received oral 2 cc thymoquinone solution for seven days at a dose of 10 mg/kg, after the induction of SAH. The rats were euthanised seven days after the first procedure. The degree of cerebral vasospasm was evaluated by measuring the basilar artery luminal area and arterial wall thickness. Apoptosis was measured by the western blot method at brainstem neural tissue. Oxidative stress was measured by the Erel Method. Endothelin-1 was measured with ELISA analysis at blood. Statistical analysis was performed.

RESULTS

Endothelin-1 values were found to be statistically significantly lower in the control and SAH+TQ groups compared to the SAH group (P < 0.001). Mean lumen area values were significantly higher in the control and SAH+TQ groups than in the SAH group (P < 0.001). In the control and SAH+TQ groups, wall thickness values decreased significantly compared to the SAH group (P < 0.001). OSI values were significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001). Apoptosis was significantly lower in the control and SAH+TQ groups than in the SAH group (P < 0.001).

CONCLUSION

Our results show that post-SAH TQ inhibits/improves DCI and cVS with positive effects on oxidative stress, apoptosis, ET-1, lumen area, and vessel wall thickness, probably due to its anti-ischaemic, antispasmodic, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective effects.

摘要

目的

蛛网膜下腔出血(SAH)患者中,迟发性脑损伤(DCI)和梗死是死亡和主要残疾的最重要原因。脑血管痉挛(cVS)和 DCI 仍然是死亡和残疾的主要原因。 百里醌(TQ)是黑种草(NS)生物活性的主要物质,对缺血性和神经退行性疾病、氧化应激、炎症事件、心血管和神经系统疾病的治疗有用。我们进行了一项实验研究,旨在研究 TQ 的预防和纠正作用。

材料和方法

24 只 Sprague-Dawley 大鼠随机分为三组。第一组是对照组,为假手术组。第二组是 SAH 组,采用双重出血性 SAH 方案诱导血管痉挛。第三组是 SAH+TQ 组,通过 SAH 方案诱导 cVS,动物在 SAH 后接受口服 2 毫升百里醌溶液,剂量为 10mg/kg,连续 7 天。第一次手术后 7 天处死大鼠。通过测量基底动脉管腔面积和动脉壁厚度来评估脑血管痉挛的程度。通过脑干部位神经组织的 Western blot 法测量细胞凋亡。通过 Erel 法测量氧化应激。通过 ELISA 分析在血液中测量内皮素-1。进行统计分析。

结果

与 SAH 组相比,对照组和 SAH+TQ 组的内皮素-1 值明显降低(P<0.001)。对照组和 SAH+TQ 组的平均管腔面积明显高于 SAH 组(P<0.001)。与 SAH 组相比,对照组和 SAH+TQ 组的壁厚度值明显降低(P<0.001)。OSI 值在对照组和 SAH+TQ 组明显低于 SAH 组(P<0.001)。对照组和 SAH+TQ 组的细胞凋亡明显低于 SAH 组(P<0.001)。

结论

我们的结果表明,SAH 后 TQ 通过对氧化应激、细胞凋亡、ET-1、管腔面积和血管壁厚度产生积极影响,抑制/改善 DCI 和 cVS,这可能归因于其抗缺血、抗痉挛、抗氧化、抗炎、抗凋亡和神经保护作用。

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