Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Gongshu, Hangzhou City, Zhejiang 310015, PR China.
Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Gongshu, Hangzhou City, Zhejiang 310015, PR China.
Tissue Cell. 2023 Oct;84:102164. doi: 10.1016/j.tice.2023.102164. Epub 2023 Jul 13.
Curcumin can regulate the polarization of microglia and alleviate traumatic brain injury (TBI). However, its detailed action mechanism on downregulating Complement 1q-like-3 protein (C1ql3) in TBI is less reported. The purpose of this study is to explore the role and mechanism of curcumin-regulated C1ql3 in TBI.
GSE23639 dataset was used to acquire gene data for microglia. C57BL/6 J wild-type (WT) mice were subjected to establish a controlled cortical impact model of TBI. The effects of curcumin (200 mg/kg) on the brain injury, inflammatory cytokine levels, microglia polarization, and C1ql3 protein expression in mice and BV-2 cells were detected by H&E staining, qRT-PCR, immunofluorescence, and Western blot, respectively. The effects of curcumin (5, 10, 20 μmol/L) and lipopolysaccharides (LPS, 1 µg/mL) on the viability of BV-2 cells were determined by MTT assay. After the transfection of C1ql3 overexpression plasmid, C1ql3 expression, IL-1β and IL-6 levels, and the number of CD16/32 and CD206 cells were determined by qRT-PCR, ELISA and flow cytometry, respectively.
C1ql3 expression was down-regulated in microglia after the curcumin treatment. Curcumin treatment could alleviate the TBI-induced brain injury in mice, reduce IL-1β and IL-6 levels, promote M2 polarization of microglia, and decrease C1ql3 protein expression. For BV-2 cells, curcumin treatment had no significant toxic effect on cell viability, but reversed the effect of LPS on cells, while C1ql3 overexpression counteracted the effect of curcumin.
Curcumin induces M2 microglia polarization through down-regulating C1ql3 expression, which may become a new treatment method for TBI.
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
姜黄素可调节小胶质细胞极化，减轻创伤性脑损伤（TBI）。然而，其下调 TBI 中补体 1q 样蛋白 3（C1ql3）的详细作用机制报道较少。本研究旨在探讨姜黄素调控 C1ql3 在 TBI 中的作用及机制。
利用 GSE23639 数据集获取小胶质细胞的基因数据。采用 C57BL/6J 野生型（WT）小鼠建立 TBI 皮质撞击模型。采用 H&E 染色、qRT-PCR、免疫荧光和 Western blot 法分别检测姜黄素（200mg/kg）对小鼠和 BV-2 细胞脑损伤、炎性细胞因子水平、小胶质细胞极化及 C1ql3 蛋白表达的影响。MTT 法检测不同浓度姜黄素（5、10、20μmol/L）和脂多糖（LPS，1μg/mL）对 BV-2 细胞活力的影响。转染 C1ql3 过表达质粒后，采用 qRT-PCR、ELISA 和流式细胞术分别检测 C1ql3 表达、IL-1β和 IL-6 水平以及 CD16/32 和 CD206 细胞数。
姜黄素处理后小胶质细胞中 C1ql3 表达下调。姜黄素处理可减轻小鼠 TBI 引起的脑损伤，降低 IL-1β和 IL-6 水平，促进小胶质细胞 M2 极化，降低 C1ql3 蛋白表达。对于 BV-2 细胞，姜黄素处理对细胞活力无明显毒性作用，但可逆转 LPS 对细胞的作用，而过表达 C1ql3 则拮抗了姜黄素的作用。
姜黄素通过下调 C1ql3 表达诱导 M2 小胶质细胞极化，可能成为 TBI 的一种新的治疗方法。
研究中生成的分析数据集可应合理要求向通讯作者索取。
