Liu Lumei, Wang Meng, Guo Menglu, Xian Li, Xu Jixiang, Xian Dehai, Zhong Jianqiao
Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People's Republic of China.
Department of Dermatology, the People's Hospital of Leshan, Southwest Medical University, Leshan, 614003, People's Republic of China.
Clin Cosmet Investig Dermatol. 2024 Mar 23;17:731-743. doi: 10.2147/CCID.S440399. eCollection 2024.
Immune-mediated inflammation and oxidative stress play pivotal roles in Henoch-Schonlein purpura (HSP), primarily through the TLR4/MyD88/NF-κB pathway. Proanthocyanidins (PCs) exert anti-inflammatory and antioxidant effects by regulating some signals like TLR4/MyD88/NF-κB. Previous research uncovered that PCs could alleviate purpura-like lesions and pathological changes on rats likely through attenuating inflammation and OS damage. The mechanism of PCs on HSP deserves further investigation.
To clarify the potential mechanism of PCs to HUVECs induced by the serum of HSP patients.
HUVECs were randomly divided into blank, control, model, and low-, medium-, and high-concentration PCs group. Then, 25% HSP serum was assigned to the latter four groups, while 25% serum from healthy subjects to control group and serum-free culture medium to blank one. The last three groups separately received different concentrations of PCs. In addition, TAK-242, a TLR4 inhibitor, was applied to investigate the effect of TLR4-related signals in PCs against HSP serum-induced damage. Finally, inflammatory and OS-related parameters were detected by using cytological/molecular-biological techniques.
Treated with HSP serum later, the levels of immuno-inflammatory and oxidative indicators obviously went up (P < 0.05), and those of antioxidants remarkably went down (P < 0.05). PCs, however, reversed above phenomena (P < 0.05). Moreover, TLR4, MyD88 and NF-κB proteins/genes highly expressed in the model group; but significantly fell off in the presence of PCs (P < 0.05). Amazingly, all of above indicators showed no significant difference among the groups of different PCs concentrations (P > 0.05). These alterations likewise occurred after TAK-242 pretreatment with or without PCs, ie a notable drop of TLR4, MyD88 and NF-κB appeared in TAK-242 presence, few differences existing when compared to the PCs groups.
PCs effectively protect HUVECs from inflammatory and OS damage provoked by HSP serum via blocking TLR4/MyD88/NF-κB signals.
免疫介导的炎症和氧化应激在过敏性紫癜（HSP）中起关键作用，主要通过TLR4/MyD88/NF-κB途径。原花青素（PCs）通过调节TLR4/MyD88/NF-κB等信号发挥抗炎和抗氧化作用。先前的研究发现，PCs可能通过减轻炎症和氧化应激损伤来缓解大鼠的紫癜样病变和病理变化。PCs对HSP的作用机制值得进一步研究。
阐明PCs对HSP患者血清诱导的人脐静脉内皮细胞（HUVECs）的潜在作用机制。
将HUVECs随机分为空白组、对照组、模型组、低、中、高浓度PCs组。后四组加入25%的HSP血清，对照组加入25%健康受试者血清，空白组加入无血清培养基。后三组分别给予不同浓度的PCs。此外，应用TLR4抑制剂TAK-242研究PCs中TLR4相关信号对HSP血清诱导损伤的影响。最后，采用细胞学/分子生物学技术检测炎症和氧化应激相关参数。
给予HSP血清后，免疫炎症和氧化指标水平明显升高（P<0.05），抗氧化剂水平显著下降（P<0.05）。然而，PCs可逆转上述现象（P<0.05）。此外，模型组中TLR4、MyD88和NF-κB蛋白/基因高表达；但在PCs存在时显著下降（P<0.05）。令人惊讶的是，不同PCs浓度组之间所有上述指标均无显著差异（P>0.05）。在有或无PCs的情况下，TAK-242预处理后也出现了同样的变化，即在TAK-242存在时，TLR4、MyD88和NF-κB显著下降，与PCs组相比差异不大。
PCs通过阻断TLR4/MyD88/NF-κB信号有效保护HUVECs免受HSP血清引起的炎症和氧化应激损伤。
