Matrine alleviating kidney injury in rats with chronic glomerulonephritis and its mechanism

WEI Huan-Bing; LI Ang; GAO Ying; LI Wei; DAI Yun-Feng

doi:10.16098/j.issn.0529-1356.2024.06.016

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Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (6) : 769-775. DOI: 10.16098/j.issn.0529-1356.2024.06.016

Histology,Embryology and Developmental Biology

Matrine alleviating kidney injury in rats with chronic glomerulonephritis and its mechanism

WEI Huan-bing LI Ang GAO Ying LI Wei DAI Yun-feng*

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Abstract

Objective To investigate the impact of matrine (Mat) on renal injury in rats with chronic glomerulonephritis by regulating the monocyte chemotactic protein-1 (MCP-1)/chemokine C-C-motif receptor 2 (CCR2) signaling pathway. Methods The rat model of chronic glomerulonephritis was established by subcutaneous injection of bovine serum albumin, the rats were randomly grouped into control group, model group, low and high dose matrine groups (Mat-L group, Mat-H group), and matrine+CCR2 group (Mat+CCR2 group), with 10 rats in each group. After continuous gavage for 4 weeks, 24-hour urine protein excretion was measured; spleen and thymus were removed and organ index was calculated; The levels of blood urea nitrogen (BUN) and serum creatinine(Scr) in the serum of each group were detected, the pathological changes of renal tissue were observed by HE staining; the levels of tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in renal tissue were detected by ELISA; Flow cytometry was applied to detect the proportion of T lymphocyte subsets in peripheral blood of rats in each group; Western blotting was applied to determine the expression of MCP-1 and CCR2 proteins. Results The spleen index and thymus index of rats in the model group rats were obviously reduced, and there were a large number of inflammatory cell infiltration in the renal tissue, the 24-hour urine protein, BUN, Scr, TNF-α, IL-6, and the expression of MCP-1 and CCR2 obviously increased, the peripheral blood T cell subpopulations CD3⁺, CD4⁺, and CD4⁺/CD8⁺ ratio obviously reduced, the proportion of CD8⁺ obviously increased (P<0.05); The spleen index and thymus index of rats in the Mat-L and Mat-H groups of rats increased, and the phenomenon of renal tissue inflammation and infiltration improved, the 24-hour urine protein, BUN, Scr, TNF-α, IL-6, and the expression of MCP-1 and CCR2 obviously decreased, the peripheral blood T cell subpopulations CD3⁺, CD4⁺, and CD4⁺/CD8⁺ ratio obviously increased, the proportion of CD8⁺ obviously decreased (P<0.05); CCR2 attenuated the effect of Mat-H on immune function in rats with chronic glomerulonephritis. Conclusion Matrine can alleviate the inflammatory damage and improve the peripheral immune function of rats with chronic glomerulonephritis, and its mechanism may be related to the inhibition of MCP-1/CCR2 signaling pathway.

Key words

Matrine

/ Bovine serum albumin / Monocyte chemotactic protein-1/chemokine receptor 2 signaling pathway / Chronic glomerulonephritis / Flow cytometry / Western blotting / Rat

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WEI Huan-bing LI Ang GAO Ying LI Wei DAI Yun-feng. Matrine alleviating kidney injury in rats with chronic glomerulonephritis and its mechanism[J]. Acta Anatomica Sinica. 2024, 55(6): 769-775 https://doi.org/10.16098/j.issn.0529-1356.2024.06.016

References

［1］ Gusev E, Solomatina L, Zhuravleva Y, et al. The pathogenesis of endstage renal disease from the standpoint of the theory of general pathological processes of inflammation［J］. Int J Mol Sci, 2021, 22(21):11453.

［2］ Cerullo D, Rottoli D, Corna D, et al. Add-on cyclic angiotensin-(1-7) with cyclophosphamide arrests progressive kidney disease in rats with ANCA associated glomerulonephritis［J］. Cells, 2022, 11(15): 2434.

［3］ Khan MAH, Hwang SH, Barnett SD, et al. Multitarget molecule, PTUPB, to treat diabetic nephropathy in rats［J］. Br J Pharmacol, 2021, 178(22): 4468-4484.

［4］ Du Q, Fu YX, Shu AM, et al. Loganin alleviates macrophage infiltration and activation by inhibiting the MCP-1/CCR2 axis in diabetic nephropathy［J］. Life Sci, 2021, 272(1): 118808.

［5］ Wang MR, Zhang XJ, Liu HC, et al. Matrine protects oligodendrocytes by inhibiting their apoptosis and enhancing mitochondrial autophagy［J］. Brain Res Bull, 2019, 153(1): 30-38.

［6］ Mahzari A, Li S, Zhou X, et al. Matrine protects against MCD-induced development of NASH via upregulating HSP72 and downregulating mTOR in a manner distinctive from metformin［J］. Front Pharmacol, 2019, 10(1): 405.

［7］ Li WW, Wang TY, Cao B, et al. Synergistic protection of matrine and lycopene against lipopolysaccharideinduced acute lung injury in mice［J］. Mol Med Rep, 2019, 20(1): 455-462.

［8］ Khan A, Shal B, Naveed M, et al. Matrine ameliorates anxiety and depression-like behaviour by targeting hyperammonemia-induced neuroinflammation and oxidative stress in CCl4 model of liver injury［J］. Neurotoxicology, 2019, 72(1): 38-50.

［9］ Xu Y, Lin H, Zheng W, et al. Matrine ameliorates adriamycin-induced nephropathy in rats by enhancing renal function and modulating Th17/Treg balance［J］. Eur J Pharmacol, 2016, 791(1): 491-501.

［10］ Lin J, Ouyang H, Liang ChL, et al. Effects of total glucosides of Paeony on kidney protection in rats with chronic glomerulonephritis［J］. Traditional Chinese Drug Research and Clinical Pharmacology, 2021, 32(10): 1425-1430. (in Chinese)

林劲, 欧阳辉, 梁春玲, 等. 白芍总苷对慢性肾小球肾炎模型大鼠的肾脏保护作用及机制研究［J］. 中药新药与临床药理, 2021, 32(10): 1425-1430.

［11］ Zhao X, Lu Y, Li S, et al. Predicting renal function recovery and short-term reversibility among acute kidney injury patients in the ICU: comparison of machine learning methods and conventional regression［J］. Ren Fail, 2022, 44(1):1326-1337.

［12］ Zhang YB, Zhang XL, Chen NH, et al. Four matrine-based alkaloids with antiviral activities against hbv from the seeds of sophora alopecuroides［J］. Org Lett, 2017,19(2):424-427.

［13］ Xiao Y, Ma D, Wang H, et al. Matrine suppresses the er-positive mcf cells by regulating energy metabolism and endoplasmic reticulum stress signaling pathway［J］. Phytother Res, 2017, 31(4): 671-679.

［14］ Kant S, Kronbichler A, Sharma P, et al. Advances in understanding of pathogenesis and treatment of immunemediated kidney disease: a review［J］. Am J Kidney Dis, 2022, 79(4): 582-600.

［15］ Wu WB, Chen W, Lin Y. Analysis of immune function in patients with chronic glomerulonephritis［J］. Experimental and Laboratory Medicine, 2021, 39(6): 1434-1436. (in Chinese)

吴文冰, 陈雯, 林一. 慢性肾小球肾炎患者免疫功能分析［J］. 实验与检验医学, 2021, 39(6): 1434-1436.

［16］ Uchida T, Ito S, Kumagai H, et al. Roles of natural killer T cells and natural killer cells in kidney injury［ J］. Int J Mol Sci, 2019, 20(10): 2487.

［17］ Ruszkowski J, Lisowska KA, Pindel M, et al. T cells in IgA nephropathy: role in pathogenesis，clinical significance and potential therapeutic target［J］. Clin Exp Nephrol, 2019, 23(3): 291-303.

［18］ Zou Y, Zhao Q, Zhang X, et al. The immunosuppressive effects and mechanisms of loureirin B on collagen-induced arthritis in rats［J］. Front Immunol, 2023, 14: 1094649.

［19］ Singh S, Anshita D, Ravichandiran V. MCP-1: function, regulation, and involvement in disease［J］. Int Immunopharmacol，2021, 101(1): 107598.

［20］ Yoshimura T. The production of monocyte chemoattractant protein-1 (MCP-1)/CCL2 in tumor microenvironments［J］. Cytokine, 2017, 98(1): 71-78.

［21］ Xu L, Sharkey D, Cantley LG. Tubular GM-CSF promotes late MCP1/CCR2-mediated fibrosis and inflammation after ischemia/reperfusion injury［J］. J Am Soc Nephrol，2019, 30(10): 1825-1840.

［22］ Moadab F, Khorramdelazad H, Abbasifard M. Role of CCL2/CCR2 axis in the immunopathogenesis of rheumatoid arthritis: latest evidence and therapeutic approaches［J］. Life Sciences, 2021, 269(1): 119034.

［23］ Lefèvre L, Iacovoni JS, Martini H, et al. Kidney inflammaging is promoted by CCR2 macrophages and tissue-derived micro-environmental factors［J］. Cell Mol Life Sci, 2021, 78(7): 3485-3501.

［24］ Kanemitsu N, Kiyonaga F, Mizukami K, et al. Chronic treatment with the (iso-)glutaminyl cyclase inhibitor PQ529 is a novel and effective approach for glomerulonephritis in chronic kidney disease［J］. Naunyn Schmiedebergs Arch Pharmacol, 2021, 394(4): 751-761.