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雷帕霉素通过改善免疫应答和功能缓解系统性红斑狼疮小鼠的肾脏损伤。

Rapamycin alleviates renal damage in mice with systemic lupus erythematosus through improving immune response and function.

机构信息

Department of Rheumatology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545027, China.

出版信息

Biomed Pharmacother. 2021 May;137:111289. doi: 10.1016/j.biopha.2021.111289. Epub 2021 Feb 12.

Abstract

This study aimed to explore the therapeutic effect and mechanism of rapamycin (RAPA) on systemic lupus erythematosus (SLE) in BALB/C mice induced by pristane. The mice were randomly divided into 5 groups (n = 6): control, model, saline, RAPA (1 mg/kg) and RAPA (2 mg/kg). All groups were injected with pristane except control. HE staining revealed 1 mg/kg and 2 mg/kg RAPA treatments obviously alleviated pathological changes in the kidney of SLE mice such as glomeruli enlargement, hyperplasia of mesangial cells, epithelial and endothelial cells, infiltration of inflammatory cells, and edema-like degeneration of renal tubules. Compared with control group, body weights and anti-ribosomal P-protein antibody (ARPA) level of the mice in model group and saline group decreased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody and urine protein in model group and saline group increased (P < 0.05). However, compared with model group and saline group, body weights of the mice in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group increased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody, ARPA, and urine protein in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group decreased (P < 0.05). Compared with control group, the proportion of dentritic cells (DC) in the kidney and peripheral blood decreased while the proportion of Th1, Th2 and Th17 cells in the spleen, kidney and peripheral blood increased in model group and saline group (P < 0.05). Compared with model group and saline group, 1 mg/kg and 2 mg/kg RAPA treatments boosted the proportion of DC in the kidney and peripheral blood, reduced the proportion of Th1 and Th17 cells in the spleen, kidney and peripheral blood, and lessened the proportion of Th2 cells in the kidney and peripheral blood (P < 0.05). In conclusion, RAPA alleviated renal damage in SLE mice through improving immune response and function.

摘要

本研究旨在探讨雷帕霉素(RAPA)对经特戊酸诱导的系统性红斑狼疮(SLE)BALB/C 小鼠的治疗作用及机制。将小鼠随机分为 5 组(n=6):对照组、模型组、生理盐水组、RAPA(1mg/kg)组和 RAPA(2mg/kg)组。除对照组外,所有组均注射特戊酸。HE 染色显示,1mg/kg 和 2mg/kg RAPA 治疗明显减轻了 SLE 小鼠肾脏的病理变化,如肾小球肿大、系膜细胞增生、上皮细胞和内皮细胞增生、炎性细胞浸润以及肾小管水肿样变性。与对照组相比,模型组和生理盐水组小鼠的体重和抗核糖体 P 蛋白抗体(ARPA)水平下降(P<0.05),而模型组和生理盐水组免疫复合物沉积以及抗双链 DNA 抗体、抗 smRNP 抗体和尿蛋白水平升高(P<0.05)。然而,与模型组和生理盐水组相比,RAPA(1mg/kg)组和 RAPA(2mg/kg)组小鼠的体重增加(P<0.05),而 RAPA(1mg/kg)组和 RAPA(2mg/kg)组免疫复合物沉积以及抗双链 DNA 抗体、抗 smRNP 抗体、ARPA 和尿蛋白水平降低(P<0.05)。与对照组相比,模型组和生理盐水组小鼠肾脏和外周血中的树突状细胞(DC)比例降低,而脾脏、肾脏和外周血中的 Th1、Th2 和 Th17 细胞比例升高(P<0.05)。与模型组和生理盐水组相比,1mg/kg 和 2mg/kg RAPA 治疗可提高肾脏和外周血中 DC 的比例,降低脾脏、肾脏和外周血中 Th1 和 Th17 细胞的比例,减少肾脏和外周血中 Th2 细胞的比例(P<0.05)。总之,RAPA 通过改善免疫反应和功能缓解了 SLE 小鼠的肾脏损伤。

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