Objective  To explore the protective effect of luteolin on acute kidney injury.

Methods  Mice with endotoxin-induced acute kidney injury model were constructed by lipopolysaccharide (LPS). Kidney-injured mice were treated with luteolin and given tail vein injection of miR-30c-5p antagomir to knock down the expression of miR-30c-5p. Animals were grouped as follows: normal control group, LPS group, lignocaine treated group (LPS+Lu group), negative control group for lignocaine treatment (LPS+DMSO group), miR-30c-5p expression knockdown group (antagomir 30c-5p group) and miR-30c-5p expression knockdown control group ( antagomir NC group). Serum cre-atinine (SCr) and blood urea nitrogen (BUN) were measured in mice by taking automated chemical analyzer, and renal histopathological damage was observed by HE staining. Serum Cystatin C (Cys-C), inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-4 levels were measured in mice using ELISA kits, and apoptosis was detected by TUNEL staining and Western blot.

Results  Compared with the normal control group, acute kidney injury pathology was more severe in the LPS group, with significantly higher expression levels of SCr, BUN and serum Cys-C, pro-inflammatory factor IL-6, TNF-α, and pro-apoptotic factor Bax protein expression level, and expression levels of an-ti-inflammatory factor IL-4, anti-apoptotic factor Bcl-2, and miR-30c-5p expression levels were significantly decreased (P<0.05). Compared with the LPS group, the pathology of kidney injury was reduced in the LPS+Lu group, and the expression levels of SCr, BUN and Cys-C, IL-6, TNF-α, and Bax were significantly reduced, while the levels of IL-4, Bcl-2, and miR-30c-5p were significantly increased (P<0.05). Compared with mice in the antagomir NC group, antagomir 30c-5p group mice owned more severe inflammation and apoptosis (P<0.05).

Conclusion  Luteolin protected mice with acute kidney injury by upregulating miR-30c-5p expression to inhibit inflammation and apoptosis.

1.Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study[J]. Intensive Care Med, 2015, 41(8): 1411-1423. DOI: 10.1007/s00134-015-3934-7.

2.杨春艳. 急诊危重患者急性肾损伤发生的Logistic回归分析[J]. 中国医学工程, 2022, 30(8): 71-74. [Yang CY. Lo-gistic regression analysis of occurrence of acute kidney injury in emergency critically ill patients[J]. China Medical Engineering, 2022, 30(8): 71-74.] DOI: 10.19338/j.issn.1672-2019.2022.08.015.

3.Peerapornratana S, Manrique-Caballero CL, Gómez H, et al. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment[J]. Kidney Int, 2019, 96(5): 1083-1099. DOI: 10.1016/j.kint.2019.05.026.

4.Koçkara A, Kayataş M. Renal cell apoptosis and new treatment options in sepsis-induced acute kidney  injury[J]. Ren Fail, 2013, 35(2): 291-294. DOI: 10.3109/0886022X.2012.744040.

5.杨朋, 钱军, 陈文飞, 等. 木犀草素对人非小细胞肺癌A549细胞凋亡及自噬的影响[J]. 中成药, 2022, 44(8): 2667-2671. [Yang P, Qian J, Chen WF, et al. Effects of luteolin on apoptosis and autophagy of human non-small cell lung cancer A549 cells[J]. Chinese Traditional Patent Medicine, 2022, 44(8): 2667-2671.] DOI: 10.3969/j.issn.1001-1528.2022.08.045.

6.Sung J, Lee J. Anti-inflammatory activity of butein and luteolin through suppression of NFκB activation and induction of heme oxygenase-1[J]. J Med Food, 2015, 18(5): 557-564. DOI: 10.1089/jmf.2014.3262.

7.Choi JS, Islam MN, Ali MY, et al. The effects of C-glycosylation of luteolin on its antioxidant, an-ti-Alzheimer's disease, anti-diabetic, and anti-inflammatory activities[J]. Arch Pharm Res, 2014, 37(10): 1354-1363. DOI: 10.1007/s12272-014-0351-3.

8.Seelinger G, Merfort I, Wölfle U, et al. Anti-carcinogenic effects of the flavonoid luteolin[J]. Molecules, 2008, 13(10): 2628-2651. DOI: 10.3390/molecules13102628.

9.Xu Y, Zhang J, Liu J, et al. Luteolin attenuate the D-galactose-induced renal damage by attenuation of oxidative stress and inflammation[J]. Nat Prod Res, 2015, 29(11): 1078-1082. DOI: 10.1080/14786419.2014.981181.

10.Yao Y, Yang J, Wang D, et al. The aqueous extract of lycopus lucidus turcz ameliorates streptozoto-cin-induced  diabetic renal damage via inhibiting TGF-β1 signaling pathway[J]. Phytomedicine, 2013, 20(13): 1160-1167. DOI: 10.1016/j.phymed.2013.06.004.

11.谭斅. 木犀草素防治无机汞诱导的肾损伤效果观察[D]. 哈尔滨: 东北农业大学, 2016.

12.谭斅. 木犀草素对鹌鹑机体影响及其缓解无机汞致肝肾损伤作用[D]. 哈尔滨: 东北农业大学, 2020.

13.Fabris L, Ceder Y, Chinnaiyan AM, et al. The potential of micrornas as prostate cancer biomarkers[J]. Eur Urol, 2016, 70(2): 312-322. DOI: 10.1016/j.eururo.2015.12.054.

14.Lu TX, Rothenberg ME. MicroRNA[J]. J Allergy Clin Immunol, 2018, 141(4): 1202-1207. DOI: 10.1016/j.jaci.2017.08.034.

15.王立, 胡春秀, 姜忠于, 等. 埃克替尼介导FXR受体通过下调miR-21水平抑制非小细胞肺癌细胞增殖及侵袭能力机制分析[J]. 中国药师, 2022, 25(7): 1133-1137. [Wang L, Hu CX, Jiang ZY, et al. Mechanism of ico-tinib-mediated FXR receptor inhibiting the proliferation and invasion of non-small cell lung cancer cells by down-regulating the level of miR-21[J]. China Pharmacist, 2022, 25(7): 1133-1137.] DOI: 10.19962/j.cnki.issn1008-049X.2022.07.001.

16.Wang X, Zhang Y, Han S, et al. Overexpression of miR-30c-5p reduces cellular cytotoxicity and inhibits the  formation of kidney stones through ATG5[J]. Int J Mol Med, 2020, 45(2): 375-384. DOI: 10.3892/ijmm.2019.4440.

17.Ge QM, Huang CM, Zhu XY, et al. Differentially expressed miRNAs in sepsis-induced acute kidney injury target  oxidative stress and mitochondrial dysfunction pathways[J]. PLoS One, 2017, 12(3): e173292. DOI: 10.1371/journal.pone.0173292.

18.Xin SB, Yan H, Ma J, et al. Protective effects of luteolin on lipopolysaccharide-induced acute renal inju-ry in mice[J]. Med Sci Monit, 2016, 22: 5173-5180. DOI: 10.12659/msm.898177.

19.Campbell A, Morris G, Heller JP, et al. Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced  seizures in immature mice[J]. Sci Rep, 2021, 11(1): 340. DOI: 10.1038/s41598-020-79350-7.

20.Li X, Yao L, Zeng X, et al. miR-30c-5p Alleviated pyroptosis during sepsis-induced acute kidney injury via  targeting TXNIP[J]. Inflammation, 2021, 44(1): 217-228. DOI: 10.1007/s10753-020-01323-9.

21.Wang Z, Wu J, Hu Z, et al. Dexmedetomidine alleviates lipopolysaccharide-induced acute kidney injury by  inhibiting p75NTR-mediated oxidative stress and apoptosis[J]. Oxid Med Cell Longev, 2020, 2020: 5454210. DOI: 10.1155/2020/5454210.  

22.Chen J, Shetty S, Zhang P, et al. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects  against endotoxin-induced acute kidney injury[J]. Toxicol Appl Pharmacol, 2014, 277(2): 118-123. DOI: 10.1016/j.taap.2014.03.017.

23.Giza DE, Fuentes-Mattei E, Bullock MD, et al. Cellular and viral microRNAs in sepsis: mechanisms of action and clinical  applications[J]. Cell Death Differ, 2016, 23(12): 1906-1918. DOI: 10.1038/cdd.2016.94.

24.He J, Zhang B, Gan H. CIDEC is involved in lps-induced inflammation and apoptosis in renal tubular epithelial cells[J]. Inflammation, 2018, 41(5): 1912-1921. DOI: 10.1007/s10753-018-0834-3.

25.Guo R, Wang Y, Minto AW, et al. Acute renal failure in endotoxemia is dependent on caspase activa-tion[J]. J Am Soc Nephrol, 2004, 15(12): 3093-3102. DOI: 10.1097/01.ASN.0000145530.73247.F5.