滋肾活血方通过干预炎症级联诱导的细胞焦亡对血管性痴呆大鼠神经血管单元中神经元损伤的保护作用。
Protective effects of Zishen Huoxue recipe against neuronal injury in the neurovascular unit of rats with vascular dementia by interfering with inflammatory cascade-induced pyroptosis.
机构信息
Department of Neurology, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China.
Teaching and Residency Program Office, Hunan Hospital of Integrated Traditional Chinese and Western Medicine, No. 58 Lushan Road, Yuelu District, Changsha 410006, Hunan Province, China.
出版信息
Neuropeptides. 2023 Dec;102:102358. doi: 10.1016/j.npep.2023.102358. Epub 2023 Jun 26.
OBJECTIVE
Chinese herbal formulas show considerable therapeutic benefits in dementia. This study specifically explored the protective action of Zishen Huoxue recipe on the neurovascular unit (NVU) of rats with vascular dementia (VD).
METHODS
VD rat models were established by permanent bilateral common carotid artery occlusion and treated with Zishen Huoxue recipe. In vitro glucose‑oxygen deprivation (OGD)-injured NVU models were established and treated with miR-124-3p agomir or rat medicated serum. The neurological damage, histopathological changes, and neuronal injury in the rat hippocampus were assessed using Morris water maze test and histological stainings. Expression of miR-124-3p was determined using RT-qPCR. The blood-brain barrier/NVU injury, cell pyroptosis, NLRP3 inflammasome activation, and release of inflammatory factors were analyzed mainly by immunofluorescence analysis, TUNEL staining, Western blot, and ELISA. QS-21 (an NLRP3 activator) was used to verify the role of miR-124-3p/NLRP3.
RESULTS
Zishen Huoxue recipe ameliorated the learning/memory deficits, neuronal injury, NVU insults, cell pyroptosis, activation of NLRP3 inflammasome, and extensive secretion of lactate dehydrogenase/IL-1β/IL-18 in VD rats. miR-124-3p was downregulated in VD rats but upregulated after treatment of this recipe. miR-124-3p overexpression ameliorated NVU insults, reduced cell pyroptosis, lowered NLRP3 inflammasome activation, and suppressed inflammatory responses in OGD-injured NVU models. NLRP3 inflammasome activation partly counteracted the amelioration effect of miR-124-3p on pyroptosis. Zishen Huoxue recipe could upregulate miR-124-3p to suppress pyroptosis and protect NVU function.
CONCLUSION
Zishen Huoxue recipe can upregulate miR-124-3p expression to repress the inflammatory cascade-evoked pyroptosis, thereby protecting against neuronal injury in the NVU of VD rats.
目的
中药方剂在痴呆症治疗中显示出显著的疗效。本研究专门探讨了滋肾活血方对血管性痴呆（VD）大鼠神经血管单元（NVU）的保护作用。
方法
通过永久性双侧颈总动脉闭塞建立 VD 大鼠模型，并给予滋肾活血方治疗。建立体外葡萄糖-氧剥夺（OGD）损伤的 NVU 模型，并给予 miR-124-3p 激动剂或大鼠含药血清处理。通过 Morris 水迷宫试验和组织学染色评估大鼠海马的神经损伤、组织病理学变化和神经元损伤。使用 RT-qPCR 测定 miR-124-3p 的表达。主要通过免疫荧光分析、TUNEL 染色、Western blot 和 ELISA 分析血脑屏障/NVU 损伤、细胞焦亡、NLRP3 炎症小体激活和炎症因子的释放。使用 QS-21（NLRP3 激活剂）验证 miR-124-3p/NLRP3 的作用。
结果
滋肾活血方改善了 VD 大鼠的学习/记忆障碍、神经元损伤、NVU 损伤、细胞焦亡、NLRP3 炎症小体激活和乳酸脱氢酶/IL-1β/IL-18 的大量释放。miR-124-3p 在 VD 大鼠中下调，但在该方剂治疗后上调。miR-124-3p 过表达改善了 NVU 损伤，减少了细胞焦亡，降低了 NLRP3 炎症小体激活，并抑制了 OGD 损伤的 NVU 模型中的炎症反应。NLRP3 炎症小体激活部分抵消了 miR-124-3p 对细胞焦亡的改善作用。滋肾活血方可以上调 miR-124-3p 以抑制细胞焦亡，从而保护 VD 大鼠 NVU 中的神经元免受损伤。
结论
滋肾活血方可以上调 miR-124-3p 的表达，抑制炎症级联反应引起的细胞焦亡，从而保护 VD 大鼠 NVU 中的神经元免受损伤。
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