芍药苷调节RIP1/RIP3/MLKL信号通路对慢性结肠炎大鼠坏死性凋亡的影响

doi:10.3969/j.issn.1006-6233.2024.10.05

Abstract
Figure/Table
References
Related Citation (3)

Download: PDF (2775 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To explore the effect of paeoniflorin (PAE) on necroptosis in chronic colitis rats by regulating the receptor-interacting protein 1 (RIP1)/receptor-interacting protein 3 (RIP3)/mixed lineage kinase domain-like protein (MLKL) signaling pathway. Methods: Healthy SD rats were randomly divided into six groups, with six rats per group: Control group, Model group, and three treatment groups with low, medium, and high doses of PAE administered via gavage for 7 days (1.25g·kg^-1·d^-1 PAE-L group, 2.5g·kg^-1·d^-1 PAE-M group, 5g·kg^-1·d^-1 PAE-H group), and a combination group with high-dose PAE gavage for 7 days plus tail vein injection of RIP1 activator for 7 days (5g·kg^-1·d^-1 PAE-H + 1.5mg·kg^-1·d^-1 Z-VAD-fmk group). A chronic colitis model was established, and after successful modeling, blood was collected from the rats via the orbital vein. Colonic mucosa tissues were collected for HE staining to observe the morphology of colon tissues; colonic mucosal damage index (CMDI) scores were analyzed; TUNEL assay was used to detect apoptosis in colon tissues; immunohistochemistry was used to detect the expression of matrix metalloproteinases (MMP-1, MMP-2) in colon tissues; ELISA was used to detect serum levels of inflammatory cytokines (IL-6, TNF-α); and western blotting was used to detect the expression of RIP1/RIP3/MLKL signaling pathway proteins in colon tissues. Results: Compared with the Control group, the Model group exhibited colonic mucosal erosion, edema, and inflammatory cell infiltration, with increased CMDI scores, apoptosis rate, IL-6, TNF-α levels, and upregulated expression of MMP-1, MMP-2, p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL proteins (P<0.05). Compared with the Model group, the PAE-L, PAE-M, and PAE-H groups showed a gradual reduction in inflammatory cell infiltration in colonic mucosa tissues, decreased CMDI scores, apoptosis rate, IL-6, TNF-α levels, and downregulated expression of MMP-1, MMP-2, p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL proteins (P<0.05). Compared with the PAE-H group, the PAE-H + Z-VAD-fmk group showed exacerbated inflammation in colonic mucosa tissues, with increased CMDI scores, apoptosis rate, IL-6, TNF-α levels, and upregulated expression of MMP-1, MMP-2, p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL proteins (P<0.05). Conclusion: Paeoniflorin can alleviate necroptosis in chronic colitis rats by inhibiting the RIP1/RIP3/MLKL signaling pathway.

Key words： Chronic colitis Paeoniflorin Receptor-interacting protein 1/receptor-interacting protein 3/mixed lineage kinase domain-like protein Necroptosis

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	MU Zhongyan
	ZHANG Jianping
	et al

Cite this article:

MU Zhongyan,ZHANG Jianping,et al. The Effect of Paeoniflorin on Necroptosis in Chronic Colitis Rats by Regulating the RIP1/RIP3/MLKL Signaling Pathway[J]. HeBei Med, 2024, 30(10): 1609-1614.

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.10.05 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I10/1609

[1] Riemschneider S,Hoffmann M,Slanina U,et al.Indol-3-carbinol and quercetin ameliorate chronic DSS-induced colitis in C57BL/6 mice by AhR-mediated anti-inflammatory mechanisms[J].Int Environ Res Public Health,2021,18(5): 2262.
[2] Ma Y,Lang X,Yang Q,et al.Paeoniflorin promotes intestinal stem cell-mediated epithelial regeneration and repair via PI3K-AKT-mTOR signalling in ulcerative colitis[J].Int Immunopharmacol,2023,119(1): 110247.
[3] Zhang Y,Li M,Li X,et al.Catalytically inactive RIP1 and RIP3 deficiency protect against acute ischemic stroke by inhibiting necroptosis and neuroinflammation[J].Cell Death Dis,2020,11(7): 565.
[4] 宋瑞婧张欣欣,高飞,等.加味升降散通过介导RIP1/RIP3/MLKL通路抑制坏死性凋亡减轻糖尿病肾病大鼠肾脏纤维化[J].中国实验方剂学杂志,2022,28(17): 33-42.
[5] 唐坤鹏,吕嘉琪,文坛,等.电针不同特定穴对慢性结肠炎大鼠的效应差异性研究[J].现代中西医结合杂志,2024,33(1): 54-59.
[6] 李兰珍,李双燕,王烨,等.芍药苷对DSS诱导的慢性溃疡性结肠炎大鼠结肠Beclin1、Bcl-2表达的影响[J].中国中医药科技,2020,27(6): 885-889.
[7] 吕向阳,任晓爽,张良,等.柚皮素下调RIP1-RIP3-MLKL信号通路抑制多囊卵巢综合征大鼠卵巢颗粒细胞凋亡[J].中国药理学通报,2024,40(3): 483-489.
[8] M'Koma AE.Inflammatory bowel disease: clinical diagnosis and surgical treatment-overview[J].Medicina (Kaunas),2022,58(5): 567.
[9] Yu W,Ilyas I,Hu X,et al.Therapeutic potential of paeoniflorin in atherosclerosis: a cellular action and mechanism-based perspective[J].Front Immunol,2022,13(1): 1072007.
[10] Zhang MY,Ma LJ,Jiang L,et al.Paeoniflorin protects against cisplatin-induced acute kidney injury through targeting Hsp90AA1-Akt protein-protein interaction[J].Ethnopharmacol,2023,310(1): 116422.
[11] Si XL,Wang Y,Song BN,et al.Potential chemoprevention of paeoniflorin in colitis-associated colorectal cancer by network pharmacology,molecular docking,and in vivo experiment[J].Chem Biodivers,2022,19(8): 202200295.
[12] Li Q,Zheng S,Niu K,et al.Paeoniflorin improves ulcerative colitis via regulation of PI3K AKT based on network pharmacology analysis[J].Exp Ther Med,2024,27(4): 125.
[13] Wang X,Jiang L,Liu XQ,et al.Paeoniflorin binds to VEGFR2 to restore autophagy and inhibit apoptosis for podocyte protection in diabetic kidney disease through PI3K-AKT signaling pathway[J].Phytomedicine,2022,106(1): 154400.
[14] Liu C,Chen Y,Cui W,et al.Inhibition of neuronal necroptosis mediated by RIP1/RIP3/MLKL provides neuroprotective effects on kaolin-induced hydrocephalus in mice[J].Cell Prolif,2021,54(9): 13108.
[15] Ling X,Zhou J,Jin T,et al.Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism[J].Front Pharmacol,2022,13(1): 870928.