RESUMEN
Acute kidney injury (AKI) is a common clinical condition that confers a risk of progression of chronic kidney disease and a high risk of death. The purpose of the current study is to investigate the anti-apoptotic and anti-fibrotic effects of Zhen-Wu-Tang (ZWT) on cisplatin (CIS)-induced renal injury and elucidate the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the PI3K/Akt signaling pathway, transforming growth factor (TGF)-ß and the Wnt/ß-catenin signaling pathway in the positive effects of Zhen-Wu-Tang on the kidneys. Wistar rats were randomly assigned into six groups of 6 rats each as follows: normal control 1; normal control 2; CIS 1 and CIS 2, which received single intraperitoneal injections of CIS (6 mg/kg); CIS+ZWT 4 and CIS+ZWT 10, which received ZWT (1 ml/100 g/day, ig) starting days after the CIS injection for 4 and 10 days, respectively. Hematoxylin-eosin (H&E) staining was performed to identify the amelioration of histopathological changes in the kidneys and apoptosis of the renal proximal tubular cells. Picrosirius red staining was used to evaluate renal fibrosis after ZWT treatment. The relationship between ZWT and the upregulation of Nrf2, phosphorylation of Akt, and the downregulation of TGF-ß and WNT/ß-catenin were determined by Western blotting. At the end of the experiment, serum was isolated from the orbital blood of rats, and blood urea nitrogen (BUN) and creatinine (Cr) levels were measured. The results showed that ZWT restored the histological alterations, aberrant collagen deposition in the kidneys and the BUN and Cr levels that were increased by CIS. Treatment with ZWT reduced the expression levels of TGF-ß and Wnt and increased the expression levels of Nrf2, PI3K and Akt in the CIS-exposed kidney tissues. Furthermore, ZWT downregulated apoptosis and fibrosis by modulating the expression levels of caspase-3, Bax and alpha-smooth muscle actin (α-SMA). In conclusion, this study provides evidence for the anti-fibrotic and anti-apoptotic roles of ZWT in CIS-induced experimental kidney injury.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Cisplatino/efectos adversos , Medicamentos Herbarios Chinos/administración & dosificación , Fibrosis/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Creatinina/orina , Fibrosis/inducido químicamente , Fibrosis/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Factor 2 Relacionado con NF-E2/biosíntesis , Ratas , Factor de Crecimiento Transformador beta1/biosíntesis , beta Catenina/biosíntesisRESUMEN
OBJECTIVE: To study the protection of Zibu Piyin Recipe (ZBPYR) on the insulin signal pathway in the hippocampus of Pi-yin deficiency diabetic encephalopathy rats and to explore its possible mechanisms. METHODS: The type 2 diabetic model was established using high fat diet and intraperitoneal injection of small dose streptozotocin (STZ). The Pi-yin deficiency model was established referring to classic compound factors. The learning and memory capabilities were tested in rats by the behavioral changes. The protein expressions of hippocampal IRE1alpha, JNK, and IRS-1 were detected using Western blot. RESULTS: There was statistical difference in the learning and memory capabilities of Pi-yin deficiency rats when compared with the blank control group (P<0.05). The learning and memory capabilities could be improved by ZBPYR. The protein expressions of hippocampal phospho-IRS-1, phospho-JNK, and total IRE1alpha were enhanced (P<0.05). But they were weakened after treatment of ZBPYR. CONCLUSIONS: ZBPYR could significantly improve the learning and memory capabilities of Pi-yin deficiency diabetic rats. Its functions might be correlated with improving the endoplasmic reticulum stress to regulate the insulin signaling pathway.
