Department of Emergency, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
Department of Neurology, The People's Hospital of Leshan, Leshan 614000, Sichuan, China.
Brain Res Bull. 2022 Mar;180:97-107. doi: 10.1016/j.brainresbull.2021.12.010. Epub 2021 Dec 27.
Ovatodiolide (OVA), a bioactive substance extracted from the bioactive component of Anisomeles indica, is reported to be endowed with anti-inflammatory properties. Nonetheless, its function in ischemia-reperfusion (I/R)-induced neurological deficits and microglial inflammation remains unclear.
A middle cerebral artery occlusion (MCAO) model was set up in SD rats, which were then dealt with varying doses of OVA. The rats' neurological functions were estimated at diverse periods postoperatively. The dry and wet method, triphenyl tetrazolium chloride (TTC) staining, and Nissl's staining were conducted to measure brain edema, cerebral infarction area and neuronal damage, respectively. Immunohistochemistry (IHC) was performed to detect neuronal apoptosis and microglial activation, and the profiles of inflammatory factors in the cerebral tissues were estimated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In-vitro assays were implemented on HT22 neuronal cells and BV2 microglia to elaborate the effect of OVA against oxygen-glucose deprivation (OGD)-mediated effects.
OVA relieved HT22 cell apoptosis and eased inflammation in BV2 microglia, which were induced by OGD. OVA mitigated NF-κB phosphorylation in BV2 cells, whereas boosted SIRT1 expression. However, inhibiting SIRT1 abolished the anti-inflammatory effects of OVA in BV2 microglia under OGD stimulation. The condition medium (CM) of OGD-treated BV2 cells enhanced HT22 cell apoptosis and damage. OVA treatment in BV2 cells relieved BV2-mediated injury on HT22 cells, which was reversed by SIRT1 inhibitor. In-vivo results revealed that OVA dose-dependently attenuated I/R rats' neurological deficits, reduced brain edema, cerebral infarction area, neuronal apoptosis and microglial overactivation. Additionally, OVA inactivated the NF-κB pathway and up-regulated SIRT1 in the I/R rat model.
OVA prevented rats from brain I/R damage by hampering neuronal apoptosis and microglial inflammation via the SIRT1-NF-κB pathway.
The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.
从土木香中提取的生物活性物质欧当归内酯（OVA）具有抗炎特性。然而，其在缺血再灌注（I/R）引起的神经功能缺损和小胶质细胞炎症中的作用尚不清楚。
建立 SD 大鼠大脑中动脉闭塞（MCAO）模型，然后用不同剂量的 OVA 处理。术后不同时间评估大鼠神经功能。干湿法、氯化三苯基四氮唑（TTC）染色和尼氏染色分别用于测量脑水肿、脑梗死面积和神经元损伤。免疫组织化学（IHC）用于检测神经元凋亡和小胶质细胞活化，定量逆转录聚合酶链反应（qRT-PCR）用于检测脑组织中炎症因子的表达谱。在 HT22 神经元细胞和 BV2 小胶质细胞中进行体外实验，以阐述 OVA 对氧葡萄糖剥夺（OGD）介导作用的影响。
OVA 减轻了 OGD 诱导的 HT22 细胞凋亡和 BV2 小胶质细胞炎症。OVA 抑制了 BV2 细胞中 NF-κB 的磷酸化，而增强了 SIRT1 的表达。然而，在 OGD 刺激下，抑制 SIRT1 消除了 OVA 在 BV2 小胶质细胞中的抗炎作用。OGD 处理的 BV2 细胞的条件培养基（CM）增强了 HT22 细胞的凋亡和损伤。OVA 在 BV2 细胞中的处理减轻了 BV2 细胞对 HT22 细胞的损伤，而 SIRT1 抑制剂则逆转了这一作用。体内结果表明，OVA 剂量依赖性地减轻了 I/R 大鼠的神经功能缺损，减少了脑水肿、脑梗死面积、神经元凋亡和小胶质细胞过度激活。此外，OVA 在 I/R 大鼠模型中激活了 SIRT1，抑制了 NF-κB 通路。
OVA 通过抑制神经元凋亡和小胶质细胞炎症来防止大鼠脑 I/R 损伤，其作用机制与 SIRT1-NF-κB 通路有关。
本研究中使用和分析的数据集合可应合理要求向通讯作者索取。
