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甘草酸和/或富血小板血浆对 II 型胶原诱导性关节炎的再生作用:靶向自噬机制标志物、炎症和氧化应激。

Regenerative effects of glycyrrhizin and/or platelet rich plasma on type-II collagen induced arthritis: Targeting autophay machinery markers, inflammation and oxidative stress.

机构信息

Medical Biochemistry Department, Faculty of Medicine, Tanta University, Egypt.

Pharmacology Department, Faculty of Medicine, Tanta University, Egypt.

出版信息

Arch Biochem Biophys. 2019 Oct 30;675:108095. doi: 10.1016/j.abb.2019.108095. Epub 2019 Aug 30.

DOI:10.1016/j.abb.2019.108095
PMID:31476301
Abstract

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease manifested by joint destruction and deformity, hence decreasing patient's life quality. The aim of the present work is to explore the mechanistic effects of glycyrrhizin (GL)and/or platelet rich plasma (PRP) treatment on collagen induced arthritis. 75 female Wistar rats were allocated into five equal groups. Group I: control group. Group II: arthritis group (A group); arthritis was induced by type-II collagen Group III: Glycyrrhizin treated group(A + GL group), Group IV: platelet rich plasma treated group(A + PRP group)and Group V: combined treatment group(A + GL + PRP group). Hind paw joint tissue levels of high-mobility group box 1 protein (HMGB-1), beclin-1 and nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity were detected by ELISA. Activities of myeloperoxidase (MPO) and catalase enzymes were determined spectrophotometrically. mRNA expression levels of microtubule associated protein light chain 3 (LC3) was detected by quantitative real time PCR. After 8 weeks treatment, there was improvement of inflammation and autophagy biomarkers by the significant reduction of HMGB-1 and beclin-1 levels, down regulation ofLC3mRNA expression. On the other hand, we monitored restoration of the anti-oxidant status through the inhibited MPO activity besides induction of both catalase and Nrf2-DNA binding activities. It could be concluded that, the mutual use of both PRP and GL had a greater effect than each alone against arthritis which is considered a novel finding that can highlight the regenerative and ameliorative effects of this combined treatmentthus launching promising avenues for RA treatment.

摘要

类风湿关节炎(RA)是一种以关节破坏和畸形为特征的全身性慢性自身免疫性疾病,从而降低了患者的生活质量。本工作的目的是探讨甘草酸(GL)和/或富血小板血浆(PRP)治疗对胶原诱导性关节炎的机制作用。将 75 只雌性 Wistar 大鼠随机分为 5 组,每组 15 只。第 I 组:对照组。第 II 组:关节炎组(A 组);关节炎由 II 型胶原诱导。第 III 组:甘草酸处理组(A+GL 组),第 IV 组:富血小板血浆处理组(A+PRP 组),第 V 组:联合治疗组(A+GL+PRP 组)。采用 ELISA 法检测各组大鼠后肢关节组织高迁移率族蛋白 1(HMGB-1)、自噬相关蛋白 1(beclin-1)和核因子(红细胞 2)相关因子 2(Nrf2)DNA 结合活性。采用分光光度法测定髓过氧化物酶(MPO)和过氧化氢酶的活性。采用实时定量 PCR 检测微管相关蛋白轻链 3(LC3)mRNA 的表达水平。经过 8 周的治疗,HMGB-1 和 beclin-1 水平显著降低,LC3mRNA 表达下调,炎症和自噬生物标志物得到改善。另一方面,我们通过抑制 MPO 活性和诱导过氧化氢酶和 Nrf2-DNA 结合活性来监测抗氧化状态的恢复。可以得出结论,PRP 和 GL 的相互使用比单独使用任何一种药物对关节炎的效果都更好,这是一个新的发现,可以突出这种联合治疗的再生和改善作用,从而为 RA 的治疗开辟有前景的途径。

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