. Clinical Significance of NLRP3 Inflammasome and Related Cell Moleculesin early Elderly Diabetic Kidney Disease
NLRP3 Inflammasome and Related Cell Moleculesin
Abstract
Backgrounds:It aims to investigate the expression level of NLRP3 inflammasome and its related cell molecules in early diabetes kidney disease (EDKD) in the elderly and its clinical application value.
Methods: From October 2021 to April 2023, 50 elderly patients with T2DM (T2DM group), 50 elderly patients with EDKD (EDKD group) and 50 elderly people who passed the health check-up (healthy group) are chosenas the study subjects. Plasma NLRP3 inflammasome and related cells (blood leukocyte count, monocyte count, lymphocyte count) molecular (NT-proBNP and others) levels are tested, and Pearson correlation analysis is utilized to explore the correlation among plasma NLRP3 inflammasome and related cells, molecules and renal function indicators (UACR, BUN, Ucr) in elderly patients with EDKD.
Results: (1) The three groups’ comparison in HbA1c, FIns, HOMA-IR, UACR, BUN, Ucr, SOD, MCP-1 and TNF-α level were with P<0.05.The levels of TG and LDL-C in the EDKD group were bigger than those in the T2DM and the healthy groups;The levels of FPG, HbA1c, FINs, HOMA-IR, UACR, SOD, MCP-1, TNF-α in the EDKD and T2DM groups werebigger than those in the healthy group, while SOD wassmaller than that in the healthy group; The levels of BUN, Ucr, hs-CRP, FPG, HbA1c, FINs, HOMA-IR, UACR, SOD, MCP-1, TNF-α in the EDKD group werebigger than those in the T2DM group, while SOD was smallerthan that in the T2DM group;The aboveresults were with P<0.05. (2)It has P<0.05 in Monocyte count, NLRP3, NT-proBNP, caspase-1, ASC and othersin the three groups.The levels of thosein the EDKD and T2DM groups were bigger than the healthy group. The levels of these indicators in the EDKD group were bigger than those in the T2DM group, and with P<0.05.These indicators in EDKD group were positively correlated with UACR, BUN, and Ucr, respectively, and with P<0.05.
Conclusion: NLRP3 inflammasome and its related molecules caspase-1, ASC, IL-1β, IL-18 level and Monocyte count raised in early senile EDKD, and were significantly correlated with the severity of EDKD.
References
References
[1]Thomas S , Karalliedde J .Diabetic kidney disease[J].Medicine, 2022, 50( 11):704-710.
[2]Kolseth IB,Reine TM,Parker K,et al.Increased levels of inflammatory mediators and proinflammatory monocytes in patients with type I diabetes mellitus and nephropathy[J].J Diabetes Complications,2017,31(1):245-252.
[3]Hugo de Luca Corrêa, Rosa T D S ,Maurílio Tiradentes Dutra,et al.Association between dynapenic abdominal obesity and inflammatory profile in diabetic older community-dwelling patients with end-stage renal disease[J].Experimental Gerontology, 2021, 146(526):1-7.
[4]Cui Q , Zhang Z , Tian X ,et al.Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating AHR/NRF2/NLRP3 Inflammasome Pathways through Indole-3-lactic Acid Production[J]. 2023,71(4):1970–1981.
[5]Narros-Fernandez P , Chioua M , Petcu S A ,et al.Synthesis and Pharmacological Evaluation of New N-Sulfonylureasas NLRP3 Inflammasome Inhibitors: Identification of a HitCompound to Treat Gout[J].Journal of Medicinal Chemistry, 2022(8):6250-6260.
[6]Wei C , Xiang W , Jiulong L ,et al.NLRP3 inflammasome activation determines the fibrogenic potential of PM 2.5 air pollution particles in the lung[J].Journal of Environmental Sciences, 2022, 111:429-441.
[7]Hu M , Lin L , Liu J ,et al.Aurantio-obtusin induces hepatotoxicity through activation of NLRP3 inflammasome signaling[J].Toxicology Letters, 2022, 354:1-13.
[8]Cao W , Wang X , Li J ,et al.NLRP3 inflammasome activation determines the fibrogenic potential of PM_(2.5) air pollution particles in the lung[J].Journal of Environmental Sciences, 2022(1):429-441.
[9]Pérez-Morales RE,Del Pino MD,Valdivielso JM,et al.Inflammation in Diabetic Kidney Disease[J].Nephron,2019,143(1):12-16.
[10]Ozeki A , Oogaki Y , Henmi Y ,et al.Elevated S100A9 in preeclampsia induces soluble endoglin and IL-1 beta secretion and hypertension via the NLRP3 inflammasome[J].Journal of hypertension, 2022,(1)40:84-93.
[11]Mezzasoma L,Antognelli C,Talesa VN.A Novel Role for Brain Natriuretic Peptide: Inhibition of IL-1β Secretion via Downregulation of NF-kB/Erk 1/2 and NALP3/ASC/Caspase-1 Activation in Human THP-1 Monocyte[J].Mediators Inflamm, 2017,2017:5858315.
[12]Karatas A, Turkmen E, Erdem E, et al. Monocyte to high-density lipoprotein cholesterol ratio in patients with diabetes mellitus and diabetic nephropathy[J]. Biomark Med,2018,12(9):953-959.
[13]Pang Y Q , Yang J , Jia C M ,et al.Hypoxic preconditioning reduces NLRP3 inflammasome expression and protects against cerebral ischemia/ reperfusion injury [J]. Neural Regeneration Research, 2022, 17(2):395-400.
[14]Xiang T , Luo X , Ye L ,et al.Klotho alleviates NLRP3 inflammasome-mediated neuroinflammation in a temporal lobe epilepsy rat model by activating the Nrf2 signaling pathway[J].Epilepsy & Behavior, 2022, 128:108509.
[15]Yang M,Luo S,Jiang N,et al.DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy[J].Front Physiol, 2021,12:659751.
[16]Zang G Y , Yin Q , Shao C ,et al.CD137 signaling aggravates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated NLRP3 inflammasome activation[J].Journal of Geriatric Cardiology, 2023, 20(3):223-237.
[17]Shahzad K,Bock F,Dong W,et al.Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy[J].Kidney Int,2015,87(1):74-84.
[18]Xu X,Zhang L,Hua F,et al.FOXM1-activated SIRT4 inhibits NF-κB signaling and NLRP3 inflammasome to alleviate kidney injury and podocyte pyroptosis in diabetic nephropathy[J].Exp Cell Res,2021,408(2):112863.
[19]He J,Sun M,Tian S.Procyanidin B2 prevents lupus nephritis development in mice by inhibiting NLRP3 inflammasome activation[J].Innate Immun,2018,24(5):307-315.
[20]Chen K,Zhang J,Zhang W,et al.ATP-P2X4 signaling mediates NLRP3 inflammasome activation: a novel pathway of diabetic nephropathy[J].Int J Biochem Cell Biol,2013,45(5):932-943.
[21]Chen K,Feng L,Hu W,et al.Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy[J].FASEB J,2019,33(3):4571-4585.
[22]Yu G , Wang J , Zhang W ,et al.NLRP3 inflammasome signal pathway involves in Vibrio harveyi-induced inflammatory response in murine peritoneal macrophages in vitro[J].Acta Biochimica et Biophysica Sinica, 2021, 53(12):1590-1601.
[23]Von Scholten BJ,Reinhard H,Hansen TW,et al.Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria[J].J Diabetes Complications,2016,30(2):248-255.
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