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Effect of Danggui Buxuetang on Podocyte Injury in Diabetic Kidney Disease Rats: An Exploration Based on RIPK1/RIPK3/MLKL Signaling Pathway / 中国实验方剂学杂志
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 41-48, 2022.
Article in Chinese | WPRIM | ID: wpr-940550
ABSTRACT
ObjectiveTo observe the effect of Danggui Buxuetang on the podocyte injury and receptor-interacting protein kinase 1/receptor-interacting protein kinase3/mixed lineage kinase domain-like protein (RIPK1/RIPK3/MLKL) signaling pathway in diabetic kidney disease (DKD) ratsand to explore its possible mechanism against DKD. MethodEight of the 50 SD rats were randomly classified intoa normal group, and the remaining were fed a high-glucose and high-fat diet for six weeks and then intraperitoneally injected with 0.035 g·kg-1streptozotocin (STZ) for inducing type 2 diabetes. After successful modeling,they were randomized into the model group,high- and low-dose (1.44,0.72 g·kg-1) Danggui Buxuetang groups, and irbesartan (0.017 g·kg-1)group. After 20 weeks of drug intervention, the fasting blood glucose (FBG), kidney index (KI),and urinary microalbumin-to-urine creatinine ratio (UACR)were detected in each group. The pathological changes in renal tissue were observed by hematoxylin-eosin (HE) staining, followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6IL-6) in renal tissue of rats were determined by enzyme-linked immunosorbent assayELISA), and the protein expression levels of RIPK1, RIPK3, and MLKL in rat kidney tissue by immunohistochemistry. The apoptosis rate of podocytes was detected by in situ nick end-labelingTUNEL) assay. The mRNA expression levels of RIPK1, RIPK3, and MLKL in kidney tissue of rats were measured by real-time fluorescence quantitative polymerase chain reactionReal-time PCR), and the protein expression levels of RIPK, RIPK3, and MLKL and podocyte marker Wilms tumor protein-1 (WT-1) in rat kidney tissue were assayed by Western blot. ResultCompared with the normal group, the model group exhibited elevated FBG, UACR, and KI (P<0.01), glomerular hypertrophy, thickened basement membrane, increased extracellular matrix, mesangial hyperplasiafoot process fusion or loss, enhanced apoptosis in renal tissue, up-regulated TNF-α and IL-6 levels (P<0.01) and RIPK1/RIPK3/MLKL mRNA and protein expression (P<0.01), and down-regulated WT-1 protein expression. Compared with the model group, Danggui Buxuetang high-dose group significantly reduced the levels of FBG, UACR, and KI, improved renal histopathology, podocyte loss, and apoptosis in renal tissue, down-regulated TNF-α and IL-6 levels and RIPK1/RIPK3/MLKL mRNA and protein expression (P<0.05, P<0.01), and up-regulated WT-1 protein expression. ConclusionDanggui Buxuetang alleviates podocyte injury and delays the development of DKD possibly by regulating the RIPK1/RIPK3/MLKL signaling pathway.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Controlled clinical trial / Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Controlled clinical trial / Prognostic study Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2022 Type: Article