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狼疮方抑制小鼠移植物抗宿主病相关性狼疮肾炎并促进肾脏 LC3 相关自噬。

Lupus Recipe inhibits cGVHD-induced lupus nephritis in mice and promote renal LC3-associated autophagy.

机构信息

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China.

出版信息

Immun Inflamm Dis. 2023 Mar;11(3):e815. doi: 10.1002/iid3.815.

DOI:10.1002/iid3.815
PMID:36988251
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10022419/
Abstract

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well-established model of SLE. LC3-associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3-associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3-associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD-induced LN, which may attribute to the increased levels of LC3-associated autophagy.

摘要

狼疮性肾炎(LN)是系统性红斑狼疮(SLE)最严重的表现之一。慢性移植物抗宿主病(cGVHD)小鼠模型是 SLE 的一种成熟模型。LC3 相关自噬在清除细胞外颗粒(包括病原体和凋亡细胞)方面起着关键作用。狼疮方(LR)是一种中药复方,已被证明对治疗 SLE 有效。在这项研究中,我们研究了 LR 或 LR 联合泼尼松对 cGVHD 小鼠模型和肾脏中 LC3 相关自噬的保护作用。将小鼠分为六组。LR 治疗组分别给予 LR 剂量为 1.15 和 2.3 g/kg/天。皮质类固醇治疗组给予泼尼松剂量为 5 mg/kg/天。联合治疗组给予 LR 剂量为 2.3 g/kg/天,泼尼松剂量为 2.5 mg/kg/天。LR 治疗可降低蛋白尿和血清甘油三酯水平,并减轻脾脏重量。LR 还可缓解肾脏的病理损伤和免疫球蛋白 G 沉积。LR 联合低剂量泼尼松可显著改善肾功能,降低血清甘油三酯、总胆固醇和脾脏重量。此外,联合治疗比单独使用 LR 更有效地缓解肾脏损伤。Western blot 显示,LR 治疗或 LR 联合泼尼松可增加肾脏组织中 Rubicon 和 Nox2 的 LC3 相关自噬蛋白和 LC3I 水平。总之,LR 抑制了 cGVHD 诱导的 LN 的表现,这可能归因于 LC3 相关自噬水平的增加。

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