RESUMO
The present study sought to investigate the amelioration effects of enzymatically synthesized docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on the high-fat diet (HFD)-induced kidney injury in mice. After 6 weeks of DHA-PS intervention, the mice's body weight in the 20 and 40 mg/kg DHA-PS groups decreased by 7.09% and 9.71%, respectively, compared to the HFD group. Especially, compared to the HFD group, 40 mg/kg DHA-PS treatment effectively reduced the levels of serum urea nitrogen by 68.48%, creatinine by 38.98%, kidney lipid accumulation (total cholesterol, triglycerides, and nonesterified fatty acids levels by 26.19%, 51.00%, and 26.11%), kidney or serum proinflammatory cytokines and enhanced the levels of kidney or serum oxidative stress parameters, except for malondialdehyde (MDA). Moreover, 40 mg/kg DHA-PS treatment decreased the expression levels of toll-like receptor 4 (TLR4) by 18.63%, IKKα by 31.81%, and p-p65 by 40.73% in the nuclear factor kappa-B pathway, thereby upregulating the expression levels of p-AMPKα by 64.93%, HSL by 99.60%, ATGL by 344.50%, PPARα by 162.02%, CPT1 by 167.95%, p-ACC1 by 144.92%, and p-SREBP1 by 1172.95%, and downregulating the expression levels of SREBP1 by 38.80%, ACC1 by 18.10%, and FAS by 82.28% in the AMPK pathway. Furthermore, our results also suggested that improving serum or kidney parameters and regulating intestinal microbial could affect each other after DHA-PS treatment. These results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury. PRACTICAL APPLICATION: Our results elucidated that DHA-PS could be a potential dietary supplement to alleviate HFD-induced kidney injury.
Assuntos
Dieta Hiperlipídica , Ácidos Docosa-Hexaenoicos , Proteínas Quinases Ativadas por AMP/genética , Animais , Colesterol , Creatinina , Citocinas , Dieta Hiperlipídica/efeitos adversos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos não Esterificados , Quinase I-kappa B , Rim/metabolismo , Malondialdeído , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Nitrogênio , PPAR alfa/genética , PPAR alfa/metabolismo , Fosfatidilserinas , Receptor 4 Toll-Like/genética , Triglicerídeos , UreiaRESUMO
Early pulmonary fibrosis is the leading cause of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, whether the renin-angiotensin system (RAS) can serve as a therapeutic target is unknown. In this study, an animal model of early pulmonary fibrosis was established via the LPS three-hit regimen. Afterwards, the animals were treated with intraperitoneal injections of Ang-(1-7), AVE0991, or A779 once per day for 20 days. The plasma and BALF AngII levels of the animals were increased, while there were no significant changes in Ang-(1-7) levels in lung tissue after LPS treatment. Furthermore, the AT1R protein levels were significantly increased and the Mas levels were significantly decreased on days 14 and 21. Administration of Ang-(1-7) downregulated LPS-induced AT1R mRNA expression, which was upregulated by A779. The expression of Mas mRNA responded in the opposite direction relative to AT1R. Moreover, LPS caused decreased levels of Mas and E-cadherin and increased AT1R, Vimentin, and Src phosphorylation levels. Ang-(1-7) or AVE0991 blocked these effects but was counteracted by A779 treatment. Our findings suggested that AngII and AT1R levels exhibit opposite dynamic trends during LPS-induced early pulmonary fibrosis, as do Ang-(1-7) and Mas. Ang-(1-7) exerts protective effects against early pulmonary fibrosis, mainly by regulating the balance between AngII and AT1R and between Ang-(1-7) and Mas and by inhibiting Src kinase activation.