Transcriptional Factors of FAT/CD36, PTP1B, SREBP-1c and HNF4A Are Involved in Dyslipidemia Following Cyclosporine a Treatment in the Liver of Rats: The Rescue Effect of Curcumin.

Q3 Veterinary
A Shirpoor, M Samadi, S Gholizadeh-Ghaleh Aziz, R Naderi
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引用次数: 0

Abstract

Cyclosporine A (CsA) is a potent immunosuppressive agent that has been reported to cause various disorders, including hepatotoxicity. However, the precise molecular mediators involved in CsA-induced liver injury remain to be fully elucidated. The present study aspires to elucidate the transcription factors implicated in lipid metabolism in the context of hepatic injury induced by cyclosporine A (CsA), both independently and in conjunction with curcumin. A total of twenty-eight male adult Wistar rats were assigned into four groups, including control (Con), sham, cyclosporine A (CsA), and cyclosporine A (CsA) + curcumin (CsA+cur). The rats were administered CsA at a dosage of 30 mg/kg and curcumin at 40 mg/kg via a gastric tube for a duration of 28 days. RT-PCR and Masson trichrome staining were used to measure related changes. The results demonstrated that CsA exposure led to a substantial upregulation of protein tyrosine phosphatase 1B (PTP1B), fatty acid translocase CD36 (FAT/CD36), and sterol regulatory element-binding protein-1c (SREBP-1c) genes, along with a notable decrease in hepatocyte nuclear factor 4 Alpha (HNF4A) gene expression compared to the control and sham groups. Furthermore, CsA treatment led to a substantial elevation in plasma lipids (LDL, cholesterol, triglycerides) and liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)), in comparison to the control and sham groups. Furthermore, fibrotic changes were detected in the CsA group through Masson trichrome staining. Curcumin consumption resulted in a considerable improvement in histological disorders and molecular mediators involved in liver injury following CsA treatment. Consequently, these findings collectively suggest that CsA can exert deleterious effects on liver tissue, manifesting as lipid homeostasis disorders, as evidenced by alterations in FAT/CD36, PTP1B, and HNF4A gene expression. The findings of this study suggest that the use of curcumin, a natural antioxidant and anti-inflammatory agent, can mitigate the adverse effects of CsA on liver tissue by restoring lipid homeostasis.

FAT/CD36、PTP1B、SREBP-1c和HNF4A转录因子参与环孢素a治疗后大鼠肝脏血脂异常:姜黄素的拯救作用
环孢素A (CsA)是一种有效的免疫抑制剂,据报道可引起各种疾病,包括肝毒性。然而,确切的分子介质参与csa诱导的肝损伤仍有待充分阐明。本研究旨在阐明在环孢素A (CsA)诱导肝损伤的背景下,与脂质代谢相关的转录因子,无论是独立的还是与姜黄素联合的。选取成年雄性Wistar大鼠28只,分为对照组(Con)、假手术组(sham)、环孢素A (CsA)、环孢素A (CsA) +姜黄素(CsA+cur) 4组。大鼠经胃管给药CsA剂量为30 mg/kg,姜黄素剂量为40 mg/kg,持续28天。RT-PCR和Masson三色染色检测相关变化。结果表明,与对照组和假手术组相比,CsA暴露导致蛋白酪氨酸磷酸酶1B (PTP1B)、脂肪酸转位酶CD36 (FAT/CD36)和胆固醇调节元件结合蛋白1c (SREBP-1c)基因大幅上调,同时肝细胞核因子4 α (HNF4A)基因表达显著降低。此外,与对照组和假手术组相比,CsA治疗导致血浆脂质(LDL、胆固醇、甘油三酯)和肝酶(丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP))显著升高。此外,CsA组通过马松三色染色检测到纤维化改变。姜黄素的摄入导致CsA治疗后肝损伤的组织学紊乱和分子介质的显著改善。因此,这些发现共同表明,CsA可以对肝组织产生有害影响,表现为脂质稳态紊乱,如FAT/CD36、PTP1B和HNF4A基因表达的改变。本研究结果提示,姜黄素作为一种天然抗氧化剂和抗炎剂,可以通过恢复脂质稳态来减轻CsA对肝组织的不良影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archives of Razi Institute
Archives of Razi Institute Veterinary-Veterinary (all)
CiteScore
1.50
自引率
0.00%
发文量
108
审稿时长
12 weeks
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