Thymosin alpha1 protects against liver injury in rats with zymosan-induced multiple organ failure

doi:10.3969/j.issn.2095-4344.3076

Abstract

Abstract: BACKGROUND: Liver injury in a multiple organ failure model causes great troubles to clinicians’ medication. Thymosin α1 is used for treating chronic hepatitis and it has obvious protective effects against liver injury.
OBJECTIVE: To investigate the protective mechanism of thymosin α1 on liver injury in a rat model of multiple organ failure, based on adiponectin (ADPN)/protein kinase B (Akt)/nuclear factor κB (NF-κB) signaling pathway.
METHODS: Male SPF Sprague-Dawley rats were randomly divided into four groups: normal group, model group, experimental group, and control group. Rats in the model group, experimental group, and control group were given intraperitoneal injection of 500 mg/kg zymosan (50 g/L) to construct the rat multiple organ failure model. Normal rats were injected intraperitoneally with equal doses of normal saline. Thirty minutes after the injection, the rats in the experimental group and the control group were injected intraperitoneally with 2 mL of thymosin α1 and ganlixin with the dose of 0.5 mg/kg daily, respectively. The normal group and the model group were injected intraperitoneally with the same dose of normal saline. After 7 days of continuous administration, liver function parameters were tested; histopathological changes of rat liver tissues and cell apoptosis were detected using hematoxylin-eosin staining and TUNEL staining; immunohistochemistry and western blot were used to detect the expression of interleukin-10, tumor necrosis factor α (TNF-α), adiponectin (ADPN), adiponectin recepror 2, AdipoR2, p-AKT and NF-κB.
RESULTS AND CONCLUSION: Compared with the normal group, the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin in the serum, the pathological scores of liver injury, the cell apoptotic rate, and the expression levek of TNF-α and NF-κB were significantly increased in the model group, while the serum levels of total protein, interleukin-10, ADPN, AdipoR2 and p-AKT were significantly reduced in the model group (all P < 0.05). Compared with the model group, the serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, the pathological scores of liver injury, and cell apoptotic rate in the experimental group and control group were significantly reduced, and the serum levels of total protein, interleukin-10, ADPN, AdipoR2 and p-AKT were significantly increased (all P < 0.05). To conclude, thymosin α1 has a protective effect on the liver of rats with multiple organ failure induced by zymosan. The mechanism is related to the ADPN/Akt/NF-κB signaling pathway. ADPN/Akt is activated and the activation of NF-κB is inhibited, then reducing the inflammatory response.

Key words: , liver, thymosin α1, multiple organs, functional failure, signaling pathway, liver injury, adiponectin

CLC Number:

Ma Minghe, Niu Yi . Thymosin alpha1 protects against liver injury in rats with zymosan-induced multiple organ failure[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(11): 1753-1758.

Figures/Tables 7

References

[1] ARMSTRONG F, MCCURDY MT, HEAVNER MS. Synthetic Cannabinoid-Associated Multiple Organ Failure: Case Series and Literature Review. Pharmacotherapy. 2019;39(4):508-513.
[2] 扈红蕾, 高健, 郭文君,等. 富氢水在黄曲霉毒素B1致大鼠肝损伤模型中的抗损伤作用[J].生理学报,2019,71(5):725-731.
[3] 吴月, 杨云梅. 微RNA-155激动剂对脓毒症小鼠肝损伤时炎症应答的影响[J]. 中华危重症医学杂志(电子版),2019,12(4):235-239.
[4] RIZZO MR, FASANO R, PAOLISSO G. Adiponectin and Cognitive Decline. Int J Mol Sci. 2020;21(6):2010-2023.
[5] 赵文霞, 张丽慧, 崔健娇,等.化痰祛湿活血方干预非酒精性脂肪性肝炎大鼠ADPN/AKT/NF-κB通路的研究[J]. 中国中西医结合杂志, 2017,37(8):961-967.
[6] 杨雪亮,张凯,孔颖,等.胸腺素α1对急性肝衰竭大鼠血浆TNF-α与IL-10的影响[J]. 西安交通大学学报(医学版),2017,38(5):665-668.
[7] SAHAN FIRAT S, TEMIZ RESITOGLU M, GUDEN DS, et al. NF-κB activation mediates LPS‐or zymosan‐induced hy potension and inflammation reversed by BAY 61-3606, a selective Syk inhibitor, in rat models of septic and non‐septic shock. Clin Exp Pharmacol Physiol. 2019;46(2): 173-182.
[8] 朱平生,孟玉,付双楠,等. CCl4致大鼠肝损伤24h生物标志物水平的变化规律[J].中国实验方剂学杂志,2019,25(2):124-128.
[9] WATANABE M, SUGAWARA A, NOGUCHI Y, et al. Jietacins, azoxy natural products, as novel NF-κB inhibitors: Discovery, synthesis, biological activity, and mode of action.Eur J Med Chem. 2019;178(6):636-647.
[10] HUANG GB, HU P, GAO JM, et al.Analysis of early treatment of multiple injuries combined with severe pelvic fracture. Chin J Traumatol. 2019; 22(3):129-133.
[11] CHUN S, KWON YB. The CCL2 elevation in primary afferent fibers produces zymosan-induced hyperalgesia through microglia-mediated neuronal activation in the spinal dorsal horn.Brain Res Bull. 2019; 149(7):53-59.
[12] YANG X, CHEN Y, ZHANG J, et al. Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure. Exp Ther Med. 2018;15(4):3231-3238.
[13] ZHOU L, PAN LC, ZHENG YG, et al. Reduction of FoxP3+ Tregs by an immunosuppressive protocol of rapamycin plus Thymalfasin and Huaier extract predicts positive survival benefits in a rat model of hepatocellular carcinoma. Ann Transl Med. 2020;8(7):472-487.
[14] WANG YD, WU LL, MA LY, et al.Chronic active EBV infection associated with NK cell lymphoma and hemophagocytic lymphohistiocytosis in a 27-year-old woman: A case report. Medicine (Baltimore). 2019;98(2):1-7.
[15] 金凡,朱盼虎,李家明,等. 吡啶查尔酮类化合物对小鼠肝纤维化的作用[J].中国药理学通报,2019,35(8):1183-1184.
[16] Arab HH, Salama SA, Eid AH, et al. Targeting MAPKs, NF-κB, and PI3K/AKT pathways by methyl palmitate ameliorates ethanol-induced gastric mucosal injury in rats. J Cell Physiol. 2019;234(12):22424-22438.
[17] Mahmoud AM, Desouky EM, Hozayen WG, et al. Mesoporous Silica Nanoparticles Trigger Liver and Kidney Injury and Fibrosis Via Altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 Signaling in Rats. Biomolecules. 2019;9(10):528-549.
[18] Zhao C, Liu L, Liu Q, et al. Fibroblast growth factor 21 is required for the therapeutic effects of Lactobacillus rhamnosus GG against fructose-induced fatty liver in mice. Mol Metab. 2019;29(11):145-157.