Ketogenic diet ameliorates inflammation by inhibiting the NLRP3 inflammasome in osteoarthritis.

Ketogenic diet ameliorates inflammation by inhibiting the NLRP3 inflammasome in osteoarthritis.
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DOI:
10.1186/s13075-022-02802-0
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发表时间:
2022-05-18
影响因子:
4.9
通讯作者:
--
中科院分区:
医学2区
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--
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核苷酸结合结构域、富含亮氨酸重复序列和含有pyrin结构域的蛋白3(NLRP 3)炎性体已被报道参与骨关节炎(OA)炎症的病理过程。在这里,我们研究了生酮饮食(KD),这已经被证明是抑制NLRP 3炎性小体激活,以阐明其对OA的保护机制在大鼠。采用前交叉韧带离断联合内侧韧带部分切除术建立大鼠膝关节OA模型。分别给予KD或标准饲料(SD)治疗8周后,取膝关节标本进行检测。KD能显著增加大鼠体内β-羟丁酸(βOHB)的含量。与SD组相比,KD组关节软骨和软骨下骨的损伤明显减轻。与假手术组相比,SD组NLRP 3炎性小体和炎性细胞因子白细胞介素-1 β(IL-1β)和IL-18的表达显著增加,而KD组则显著降低。此外,KD组MMP 13较SD组显著降低,而COL 2显著升高。KD可以通过抑制NLRP 3炎性体活化和减轻OA炎症反应来保护大鼠OA模型中的关节软骨和软骨下骨。
The nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been reported to be involved in the pathological process of osteoarthritis (OA) inflammation. Here, we investigated the ketogenic diet (KD), which has been previously demonstrated to inhibit NLRP3 inflammasome activation, to elucidate its protective mechanism against OA in rats. Anterior cruciate ligament transaction (ACLT) together with partial medial meniscectomy was used to create a rat knee joint OA model. After treatment with KD or standard diet (SD) for 8 weeks, the knee specimens were obtained for testing. The KD significantly increased the content of β-hydroxybutyrate (βOHB) in rats. Compared to the SD group, the KD significantly reduced the damage caused by OA in the articular cartilage and subchondral bone. The NLRP3 inflammasome and inflammatory cytokines interleukin-1 β (IL-1β) and IL-18 were significantly increased in the SD group compared with the sham group, while their expression was significantly decreased in rats treated with the KD. In addition, MMP13 was significantly decreased in the KD group compared to that in the SD group, while COL2 was significantly increased. KD can protect the articular cartilage and subchondral bone in a rat OA model by inhibiting NLRP3 inflammasome activation and reducing the OA inflammatory response.
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