1.Huaiqihuang Granules Affect Differentiation of Th17 Cells in IgA Vasculitis Nephritis Mice by Regulating AMPK/ACC Pathway
Xinglan YE ; Keying LI ; Jiaxuan LI ; Juan BAI ; Wencheng XU ; Hong LIU ; Xue XUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):78-86
ObjectiveTo observe the intervention effect of Huaiqihuang granules (HQH) on immunoglobulin A vasculitis nephritis (IgAVN) mice and explore the underlying therapeutic mechanism. MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group, an IgAVN model group, a dexamethasone group (2.5 mg·kg-1·d-1), a low-dose HQH group (4 g·kg-1·d-1), and a high-dose HQH group (8 g·kg-1·d-1). The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling, the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein (24 h UTP), urine β2-microglobulin (β2-MG), serum total protein, albumin, IgA, etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 (Th17) cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α (AMPKα), phosphorylated AMPKα (p-AMPKα), acetyl-CoA carboxylase 1 (ACC1), and phosphorylated ACC1 (p-ACC1) in Th17 cells. Pathological changes in the spleen and kidneys were observed. ResultCompared with the normal group, the IgAVN model group showed significant increases in 24 h UTP, urine β2-MG, total cholesterol (P<0.05), serum interleukin-17 (IL-17), IgA, Th17 proportion in the spleen cell suspension, and IL-17 expression in the spleen tissue (P<0.01), and significantly decreased serum total protein, albumin, p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.01). Compared with the IgAVN model group, in the 4th week, the 24 h UTP, urine β2-MG, serum IL-17, IgA levels, and renal IgA deposition were significantly reduced in each treatment group (P<0.01), and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased (P<0.05, P<0.01). Serum albumin levels significantly increased (P<0.05). Compared with the IgAVN model group, the dexamethasone group and the high-dose HQH group showed increases in serum total protein (P<0.01), p-AMPKα/AMPKα, and p-ACC1/ACC1 expression of Th17 cells (P<0.05, P<0.01). The high-dose HQH group showed a significant decrease in total cholesterol level (P<0.05). Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes. ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway, correcting immune inflammatory disorders, and exerting therapeutic effects on IgAVN.