Diagnostic value of nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory body and sphingosine-1-phosphate in early diabetic nephropathy and its progression_West China Medical Journal

Authors：

LIN Yan ¹ , LI Jing ¹ , YU Xiangyou ¹ , LIU Lingjiao ¹ , YAN Ni ¹ ,  DUAN Chaoyang ²

1. Department of Endocrinology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, P. R. China;
2. Department of Nephrology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710004, P. R. China;

Corresponding?author：

DUAN Chaoyang, Email: duanzhaoyang2005@yeah.net

Keywords：

Nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory body; sphingosine-1-phosphate; diabetic nephropathy; early diabetic nephropathy; diagnostic value

DOI：

10.7507/1002-0179.202108088

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the diagnostic value of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory body and sphingosine-1-phosphate (S1P) in early diabetic nephropathy and its progression. Methods A total of 600 diabetic patients who were treated in Shaanxi Provincial People’s Hospital between January 2018 and December 2020 were selected, and the patients were divided into simple diabetes group, early diabetic nephropathy group and clinical diabetic nephropathy group. The expression of NLRP3 messenger RNA (mRNA) in fasting venous blood mononuclear cells was detected by real-time fluorescence quantitative polymerase chain reaction, and the level of S1P was detected by enzyme-linked immunosorbent assay double-antibody sandwich method. Pearson correlation analysis was used to explore the correlation between blood NLRP3 mRNA and S1P levels. The receiver operating characteristic curve was used to evaluate the diagnostic value of blood NLRP3 mRNA and S1P levels in early diabetic nephropathy and clinical diabetic nephropathy. Results Among the 600 diabetic patients, 205 were in the simple diabetes group, 198 in the early diabetic nephropathy group and 197 in the clinical diabetic nephropathy group. There was no significant difference in age and gender among the three groups (P>0.05). The blood levels of NLRP3 mRNA and S1P in the clinical diabetic nephropathy group were higher than those in the early diabetic nephropathy group and the simple diabetes group, the blood NLRP3 mRNA and S1P levels in the early diabetic nephropathy group were higher than those in the simple diabetes group. The differences were statistically significant, and the blood NLRP3 mRNA levels of the three groups were 2.69±0.64 vs. 2.05±0.56 vs. 1.76±0.51, and the S1P levels were (1.49±0.27) vs. (1.16±0.13) vs. (0.89±0.07) μmol/L (P<0.05). There was a positive correlation between blood NLRP3 mRNA and S1P level in patients (r=0.455, P<0.001). Blood NLRP3 mRNA, S1P levels and their combined detection can be used to diagnose whether diabetic patients develop early diabetic nephropathy (area under the receiver operating characteristic curve were 0.645, 0.968, 0.971; P<0.001) and whether it progressed to clinical diabetic nephropathy (area under the receiver operating characteristic curve were 0.825, 0.918, and 0.945; P<0.001). Conclusion Blood NLRP3 mRNA and S1P levels can be used to diagnose early diabetic nephropathy and evaluate its disease progression.

Citation： LIN Yan, LI Jing, YU Xiangyou, LIU Lingjiao, YAN Ni, DUAN Chaoyang. Diagnostic value of nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory body and sphingosine-1-phosphate in early diabetic nephropathy and its progression. West China Medical Journal, 2022, 37(7): 1035-1040. doi: 10.7507/1002-0179.202108088 Copy

1.	張杜丹, 唐迅, 靳丹瑤, 等. 中國成年人糖尿病患病率 Meta 分析. 中華流行病學雜志, 2018, 39(6): 852-857.
2.	郝玉婷, 林潔, 秦杰. 聯合檢測標志物在糖尿病腎病早期腎損傷診斷中的臨床價值. 西部醫學, 2018, 30(10): 1535-1538, 1546.
3.	徐靜, 胡曉帆, 黃威, 等. 糖尿病腎病與伴糖尿病的非糖尿病腎臟疾病患者臨床病理特征分析. 中華內科雜志, 2017, 56(12): 924-929.
4.	程龍飛, 章金燦, 黃澤偉, 等. 糖化血紅蛋白聯合尿微量白蛋白檢測對糖尿病腎病早期診斷的臨床價值. 中華臨床醫師雜志(電子版), 2016, 10(16): 2382-2385.
5.	Wang S, Li Y, Fan J, et al. Interleukin-22 ameliorated renal injury and fibrosis in diabetic nephropathy through inhibition of NLRP3 inflammasome activation. Cell Death Dis, 2017, 8(7): e2937.
6.	張婧瑤, 劉衛東, 劉函曄, 等. 1-磷酸鞘氨醇與相關疾病的研究進展. 生理科學進展, 2019, 50(3): 200-204.
7.	葛均波, 徐永健, 王辰. 內科學. 9 版. 北京: 人民衛生出版社, 2018: 735-734.
8.	郭思若, 張愛華. 糖尿病腎病的診斷及鑒別診斷. 中華全科醫師雜志, 2017, 16(10): 750-752.
9.	Strelitz J, Ahern AL, Long GH, et al. Changes in behaviors after diagnosis of type 2 diabetes and 10-year incidence of cardiovascular disease and mortality. Cardiovasc Diabetol, 2019, 18(1): 98.
10.	楊宏秀, 張會芬, 劉麗, 等. 血清 NGAL、TRF、hs-CRP 及 SF 在糖尿病腎病診斷中的價值. 山東醫藥, 2017, 57(46): 50-52.
11.	Lu H, Deng S, Zheng M, et al. iTRAQ plasma proteomics analysis for candidate biomarkers of type 2 incipient diabetic nephropathy. Clin Proteomics, 2019, 16: 33.
12.	Feng H, Gu J, Gou F, et al. High glucose and lipopolysaccharide prime NLRP3 inflammasome via ROS/TXNIP pathway in mesangial cells. J Diabetes Res, 2016, 2016: 6973175.
13.	El-Horany HE, Abd-Ellatif RN, Watany M, et al. NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients. IUBMB Life, 2017, 69(8): 623-630.
14.	周路平, 黃煒, 徐勇, 等. 甜味受體在糖尿病腎病 NLRP3 炎癥信號活化中的作用. 中華內分泌代謝雜志, 2018, 34(7): 587-593.
15.	Zhang C, Boini KM, Xia M, et al. Activation of nod-like receptor protein 3 inflammasomes turns on podocyte injury and glomerular sclerosis in hyperhomocysteinemia. Hypertension, 2012, 60(1): 154-162.
16.	Gao C, Chen J, Fan F, et al. RIPK2-mediated autophagy and negatively regulated ROS-NLRP3 inflammasome signaling in GMCs stimulated with high glucose. Mediators Inflamm, 2019, 2019: 6207563.
17.	Hou Y, Lin S, Qiu J, et al. NLRP3 inflammasome negatively regulates podocyte autophagy in diabetic nephropathy. Biochem Biophys Res Commun, 2020, 521(3): 791-798.
18.	毛海霞, 歐三桃. NLRP3 炎性小體與糖尿病腎病的研究進展. 西南軍醫, 2021, 23(1): 30-34.
19.	Chen K, Feng L, Hu W, et al. Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy. FASEB J, 2019, 33(3): 4571-4585.
20.	Feng H, Zhu X, Tang Y, et al. Astragaloside IV ameliorates diabetic nephropathy in db/db mice by inhibiting NLRP3 inflammasome-mediated inflammation. Int J Mol Med, 2021, 48(2): 164.
21.	Zhang L, Jing M, Liu Q. Crocin alleviates the inflammation and oxidative stress responses associated with diabetic nephropathy in rats via NLRP3 inflammasomes. Life Sci, 2021, 278: 119542.
22.	蔣東波, 張小燕. 糖尿病腎病患者腎臟活檢組織中 NLRP3 炎癥小體表達水平與腎損害的關系. 熱帶醫學雜志, 2021, 21(1): 99-102, 封 4.
23.	黃秀麗, 吳艷, 王超平, 等. 老年糖尿病腎病患者外周血 NLRP3 炎性體與腎損傷指標的相關性分析. 老年醫學與保健, 2017, 23(6): 496-498.
24.	Lan T, Liu W, Xie X, et al. Sphingosine kinase-1 pathway mediates high glucose-induced fibronectin expression in glomerular mesangial cells. Mol Endocrinol, 2011, 25(12): 2094-2105.
25.	Awad AS, Rouse MD, Khutsishvili K, et al. Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes. Kidney Int, 2011, 79(10): 1090-1098.
26.	Chen C, Gong W, Li C, et al. Sphingosine kinase 1 mediates AGEs-induced fibronectin upregulation in diabetic nephropathy. Oncotarget, 2017, 8(45): 78660-78676.
27.	El-Shewy HM, Sohn M, Wilson P, et al. Low-density lipoprotein induced expression of connective tissue growth factor via transactivation of sphingosine 1-phosphate receptors in mesangial cells. Mol Endocrinol, 2012, 26(5): 833-845.
28.	李林徽, 張瑾, 尹建紅, 等. T 淋巴細胞 CD69 抗原表達水平和 S1P、TGF-β1 等細胞因子在糖尿病腎病中的研究進展. 中西醫結合心腦血管病雜志, 2020, 18(4): 590-593.
29.	Bekpinar S, Yenidunya G, Gurdol F, et al. The effect of nephropathy on plasma sphingosine 1-phosphate concentrations in patients with type 2 diabetes. Clin Biochem, 2015, 48(18): 1264-1267.
30.	趙郁松, 馬毓敏, 梅笑雪. 血清淋巴管生成因子介導糖尿病腎病進展的相關性. 廣西醫科大學學報, 2022, 39(1): 127-131.
31.	Imasawa T, Kitamura H, Ohkawa R, et al. Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy. Exp Toxicol Pathol, 2010, 62(1): 53-60.

1. 張杜丹, 唐迅, 靳丹瑤, 等. 中國成年人糖尿病患病率 Meta 分析. 中華流行病學雜志, 2018, 39(6): 852-857.
2. 郝玉婷, 林潔, 秦杰. 聯合檢測標志物在糖尿病腎病早期腎損傷診斷中的臨床價值. 西部醫學, 2018, 30(10): 1535-1538, 1546.
3. 徐靜, 胡曉帆, 黃威, 等. 糖尿病腎病與伴糖尿病的非糖尿病腎臟疾病患者臨床病理特征分析. 中華內科雜志, 2017, 56(12): 924-929.
4. 程龍飛, 章金燦, 黃澤偉, 等. 糖化血紅蛋白聯合尿微量白蛋白檢測對糖尿病腎病早期診斷的臨床價值. 中華臨床醫師雜志(電子版), 2016, 10(16): 2382-2385.
5. Wang S, Li Y, Fan J, et al. Interleukin-22 ameliorated renal injury and fibrosis in diabetic nephropathy through inhibition of NLRP3 inflammasome activation. Cell Death Dis, 2017, 8(7): e2937.
6. 張婧瑤, 劉衛東, 劉函曄, 等. 1-磷酸鞘氨醇與相關疾病的研究進展. 生理科學進展, 2019, 50(3): 200-204.
7. 葛均波, 徐永健, 王辰. 內科學. 9 版. 北京: 人民衛生出版社, 2018: 735-734.
8. 郭思若, 張愛華. 糖尿病腎病的診斷及鑒別診斷. 中華全科醫師雜志, 2017, 16(10): 750-752.
9. Strelitz J, Ahern AL, Long GH, et al. Changes in behaviors after diagnosis of type 2 diabetes and 10-year incidence of cardiovascular disease and mortality. Cardiovasc Diabetol, 2019, 18(1): 98.
10. 楊宏秀, 張會芬, 劉麗, 等. 血清 NGAL、TRF、hs-CRP 及 SF 在糖尿病腎病診斷中的價值. 山東醫藥, 2017, 57(46): 50-52.
11. Lu H, Deng S, Zheng M, et al. iTRAQ plasma proteomics analysis for candidate biomarkers of type 2 incipient diabetic nephropathy. Clin Proteomics, 2019, 16: 33.
12. Feng H, Gu J, Gou F, et al. High glucose and lipopolysaccharide prime NLRP3 inflammasome via ROS/TXNIP pathway in mesangial cells. J Diabetes Res, 2016, 2016: 6973175.
13. El-Horany HE, Abd-Ellatif RN, Watany M, et al. NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients. IUBMB Life, 2017, 69(8): 623-630.
14. 周路平, 黃煒, 徐勇, 等. 甜味受體在糖尿病腎病 NLRP3 炎癥信號活化中的作用. 中華內分泌代謝雜志, 2018, 34(7): 587-593.
15. Zhang C, Boini KM, Xia M, et al. Activation of nod-like receptor protein 3 inflammasomes turns on podocyte injury and glomerular sclerosis in hyperhomocysteinemia. Hypertension, 2012, 60(1): 154-162.
16. Gao C, Chen J, Fan F, et al. RIPK2-mediated autophagy and negatively regulated ROS-NLRP3 inflammasome signaling in GMCs stimulated with high glucose. Mediators Inflamm, 2019, 2019: 6207563.
17. Hou Y, Lin S, Qiu J, et al. NLRP3 inflammasome negatively regulates podocyte autophagy in diabetic nephropathy. Biochem Biophys Res Commun, 2020, 521(3): 791-798.
18. 毛海霞, 歐三桃. NLRP3 炎性小體與糖尿病腎病的研究進展. 西南軍醫, 2021, 23(1): 30-34.
19. Chen K, Feng L, Hu W, et al. Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy. FASEB J, 2019, 33(3): 4571-4585.
20. Feng H, Zhu X, Tang Y, et al. Astragaloside IV ameliorates diabetic nephropathy in db/db mice by inhibiting NLRP3 inflammasome-mediated inflammation. Int J Mol Med, 2021, 48(2): 164.
21. Zhang L, Jing M, Liu Q. Crocin alleviates the inflammation and oxidative stress responses associated with diabetic nephropathy in rats via NLRP3 inflammasomes. Life Sci, 2021, 278: 119542.
22. 蔣東波, 張小燕. 糖尿病腎病患者腎臟活檢組織中 NLRP3 炎癥小體表達水平與腎損害的關系. 熱帶醫學雜志, 2021, 21(1): 99-102, 封 4.
23. 黃秀麗, 吳艷, 王超平, 等. 老年糖尿病腎病患者外周血 NLRP3 炎性體與腎損傷指標的相關性分析. 老年醫學與保健, 2017, 23(6): 496-498.
24. Lan T, Liu W, Xie X, et al. Sphingosine kinase-1 pathway mediates high glucose-induced fibronectin expression in glomerular mesangial cells. Mol Endocrinol, 2011, 25(12): 2094-2105.
25. Awad AS, Rouse MD, Khutsishvili K, et al. Chronic sphingosine 1-phosphate 1 receptor activation attenuates early-stage diabetic nephropathy independent of lymphocytes. Kidney Int, 2011, 79(10): 1090-1098.
26. Chen C, Gong W, Li C, et al. Sphingosine kinase 1 mediates AGEs-induced fibronectin upregulation in diabetic nephropathy. Oncotarget, 2017, 8(45): 78660-78676.
27. El-Shewy HM, Sohn M, Wilson P, et al. Low-density lipoprotein induced expression of connective tissue growth factor via transactivation of sphingosine 1-phosphate receptors in mesangial cells. Mol Endocrinol, 2012, 26(5): 833-845.
28. 李林徽, 張瑾, 尹建紅, 等. T 淋巴細胞 CD69 抗原表達水平和 S1P、TGF-β1 等細胞因子在糖尿病腎病中的研究進展. 中西醫結合心腦血管病雜志, 2020, 18(4): 590-593.
29. Bekpinar S, Yenidunya G, Gurdol F, et al. The effect of nephropathy on plasma sphingosine 1-phosphate concentrations in patients with type 2 diabetes. Clin Biochem, 2015, 48(18): 1264-1267.
30. 趙郁松, 馬毓敏, 梅笑雪. 血清淋巴管生成因子介導糖尿病腎病進展的相關性. 廣西醫科大學學報, 2022, 39(1): 127-131.
31. Imasawa T, Kitamura H, Ohkawa R, et al. Unbalanced expression of sphingosine 1-phosphate receptors in diabetic nephropathy. Exp Toxicol Pathol, 2010, 62(1): 53-60.

West China Medical Journal

Diagnostic value of nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory body and sphingosine-1-phosphate in early diabetic nephropathy and its progression

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content