柚皮素对人角膜上皮细胞毒性的实验研究

doi:10.3877/cma.j.issn.2095-2007.2021.01.007

目的

探讨柚皮素(Nar)对人角膜上皮细胞(HCECs)的毒性。

方法

对购于青旗上海生物技术发展有限公司的HCECs进行细胞毒性实验和划痕实验。应用四氮唑盐比色分析法检测二甲基亚砜(DMSO)溶剂和Nar对HCECs细胞存活率的影响，采用Graphpad Prism8.0软件绘制细胞存活率曲线并计算半抑制浓度(IC₅₀)。应用划痕实验观察不同浓度Nar对HCECs迁移的影响，采用ImageJ软件计算细胞的愈合率。吸光度值、存活率及愈合率数值符合正态分布，均采用均数±标准差表示。不同浓度的DMSO溶剂和Nar溶液对HCECs 24 h、48 h及72 h存活率的比较；不同浓度Nar对HCECs 6 h、12 h及24 h划痕愈合率的比较，均采用独立样本t检验。

结果

体积百分比为0.04%、0.08%及0.16%的DMSO处理HCECs 24 h，其存活率分别为(94.57±0.83)%、(93.59±1.17)%及(91.43±1.47)%。经t检验，各浓度DMSO处理HCECs 24 h，其存活率与DMEM(dulbecco′s modified eagle medium)组比较的差异均有统计学意义(t＝3.436，3.882，4.960；P<0.05)。体积百分比为0.08%和0.16%的DMSO处理HCECs 48 h，其存活率分别为(94.43±0.38)%和(93.16±0.66)%。经t检验，各浓度DMSO处理HCECs 48 h，其与DMEM组比较存活率的差异均有统计学意义(t＝2.953，3.573；P<0.05)。体积百分比为0.02%、0.04%、0.08%及0.16%的DMSO处理HCECs 72 h，其存活率分别为(96.28±0.29)%、(95.30±0.25)%、(94.65±0.82)%及(93.73±1.18)%。经t检验，各浓度DMSO处理HCECs 72 h，其与DMEM组比较存活率的差异均有统计学意义(t＝3.756，4.763，4.929，5.263；P<0.05)。200 μM、400 μM及800 μM Nar溶液处理HCECs 48 h，其存活率分别为(60.17±0.46)%、(47.55±0.91)%及(29.19±1.25)%；72 h的存活率分别为(60.02±6.20)%、(31.20±1.96)%及(22.96±2.69)%。经t检验，各浓度Nar处理HCECs 48 h和72 h，其与24 h比较存活率的差异均有统计学意义(t＝12.903，6.675, 11.215，5.377，12.696，11.972；P<0.05)。25 μM、400 μM及800 μM Nar溶液处理HCECs 72 h，其存活率分别为(89.41±1.38)%、(31.20±1.96)%及(22.96±2.69)%。经t检验，各浓度Nar溶液处理HCECs 72 h，其与48 h比较存活率的差异均有统计学意义(t＝4.442，13.119，3.631；P<0.05)。Nar溶液对HCECs 24 h、48 h及72 h的IC₅₀分别为690.8 μM、343.4 μM及237.7 μM；IC₅₀ 95%可信区间分别为(574.1~845.5)、(259.2~734.3)及(231.1~266.7)。HCECs在0、100 μM、200 μM及400 μM Nar溶液中HCECs 6 h的划痕愈合率分别为(18.04±1.61)%、(16.91±1.56)%、(16.63±2.12)%及(12.20±2.06)%。划痕愈合的时间越长，HCECs的愈合率越高。细胞在100 μM Nar溶液浓度中各时间段的划痕愈合率与DMEM组比较的差异均无统计学意义(t＝0.872，1.074，1.620；P>0.05)；400 μM Nar溶液各时间段的划痕愈合率与DMEM组比较的差异均有统计学意义(t＝3.863，9.869，27.194；P<0.05)；200 μM Nar溶液处理HCECs 12 h和24 h，其划痕愈合率与DMEM组比较的差异均有统计学意义(t＝5.714，9.119；P<0.05)。

结论

Nar可降低HCECs存活率并抑制HCECs迁移愈合率，对HCECs具有毒性。

关键词: 人角膜上皮细胞, 柚皮素, 二甲基亚砜, 毒性

Objective

The aim of this study was to investigate the toxicity of naringenin (Nar) to human corneal epithelial cells (HCECs).

Methods

HCECs purchased from Qingqi Shanghai Biotechnology Development Co., Ltd. were used for cytotoxicity test and scratch test. The tetrazolium salt colorimetric assay was used to detect the cell survival of Nar and DMSO on HCECs. Graphpad Prism8.0 software was used to map the cells survival curve and calculate the half inhibitory concentration (IC₅₀). The scratch experiment was used to observe the effect of different concentrations of Nar on the migration of HCECs. ImageJ was used to calculate the cell healing rate (HR). OD value, survival rate (SR) and HR were in accordance with normal distribution, and expressed by ±s.The independent sample t-testing method was used to compare SR of HCECs with different concentrations of DMSO solvent and Nar solution for 24 h, 48 h and 72 h; and the wound HR of cells at 6 h, 12 h and 24 h with different concentrations of Nar.

Results

The SR of HCECs in the DMSO 0.04%, 0.08% and 0.16% groups for 24 h was (94.57±0.83)%, (93.59±1.17)% and (91.43±1.47)%, respectively. After t testing, compared with the DMEM group, the difference in the SR of HCECs was statistically significant (t=3.436, 3.882, 4.960; P<0.05). The SR of HCECs was (94.43±0.38)% and (93.16±0.66)% in the DMSO group with a volume percentage of 0.08% and 0.16% for 48 h. After t testing, compared with the DMEM group, the difference in the SR of HCECs was statistically significant (t=2.953, 3.573; P<0.05). In the DMSO group with the volume percentage of 0.02%, 0.04%, 0.08% and 0.16% for 72 h, the SRs of HCECs were (96.28±0.29)%, (95.30±0.25)%, (94.65±0.82)% and (93.73±1.18)%. After t testing, the difference in the SR of HCECs between different DMSO volume percentage and the DMEM group was statistically significant (t=3.756, 4.763, 4.929, 5.263; P<0.05). The SRs of HCECs treated with 200 μM, 400 μM and 800 μM Nar solutions for 48 h were (60.17±0.46)%, (47.55±0.91)% and (29.19±1.25)%, respectively; the SRs at 72 h were ( 60.02±6.20)%, (31.20±1.96)% and (22.96±2.69)%. After t testing, the difference in SR of HCECs for 48 h and 72 h compared with that for 24 h, was statistically significant (t=12.903, 6.675, 11.215, 5.377, 12.696, 11.972; P<0.05). The SRs of HCECs treated with 25 μM, 400 μM and 800 μM Nar solutions for 72 h were (89.41±1.38)%, (31.20±1.96)% and (22.96±2.69)%, respectively. After t testing, the SR of HCECs for 72 h compared with that for 48 h was significantly different (t=4.442, 13.119, 3.631; P<0.05). The IC₅₀ of Nar solution for HCECs at 24 h, 48 h and 72 h was 690.8 μM, 343.4 μM and 237.7 μM, respectively, and the 95% confidence intervals of IC₅₀ were (574.1 to 845.5), (259.2 to 734.3) and (231.1 to 266.7). The migration area coverage rate of HCECs for 6 h in 0, 100 μM, 200 μM and 400 μM Nar solutions were (18.04±1.61)%, (16.91±1.56)%, (16.63±2.12)% and (12.20±2.06) %, respectively. The migration area coverage rate of HCECs gradually increased with time. Compared with the DMEM group, there was no significant difference in the migration area coverage rate of cells added with 100 μM Nar solution in per time period (t=0.872, 1.074, 1.620; P>0.05); the difference in that of cells added with 400 μM Nar was statistically significant (t=3.863, 9.869, 27.194; P<0.05); the difference in the scar HR of HCECs added with 200 μM Nar after scratching for 12 h and 24 h was significantly different (t=5.714, 9.119; P<0.05).

Conclusions

Nar could reduce the SR of HCECs and inhibit the migration and HR of HCECs, which is toxic to HCECs.

Key words: Human corneal epithelial cells, Naringenin, Dimethyl sulfoxide, Toxicity

表1 不同浓度二甲基亚砜中24 h、48 h及72 h细胞存活率的比较(±s)

项目	0	0.0025%DMSO	0.005%DMSO	0.01%DMSO	0.02%DMSO	0.04%DMSO	0.08%DMSO	0.16%DMSO
24 h OD值	0.415±0.011	0.412±0.108	0.409±0.011	0.406±0.012	0.403±0.012	0.398±0.013	0.395±0.014	0.389±0.012
存活率(%)	100.00±2.61	98.92±0.48	98.05±0.55	97.18±0.53	95.98±0.61	94.57±0.83^*	93.59±1.17^*	91.43±1.47^*
t值		0.704	1.266	1.836	2.598	3.436	3.882	4.960
P值		>0.05	>0.05	>0.05	>0.05	<0.05	<0.05	<0.05
48 h OD值	0.477±0.016	0.474±0.015	0.470±0.016	0.467±0.015	0.464±0.015	0.461±0.014	0.456±0.014	0.452±0.013
存活率(%)	100.00±3.25	99.10±0.12	98.11±0.07	97.30±0.20	96.50±0.45	95.60±0.54	94.43±0.38^*	93.16±0.66^*
t值		0.479	1.009	1.436	1.851	2.315	2.953	3.573
P值		>0.05	>0.05	>0.05	>0.05	>0.05	<0.05	<0.05
72 h OD值	0.615±0.010	0.610±0.010	0.605±0.010	0.601±0.015	0.596±0.010	0.591±0.009	0.588±0.010	0.583±0.012
存活率(%)	100.00±1.69	98.96±0.08	98.04±0.06	97.19±0.19	96.28±0.29^*	95.30±0.25^*	94.65±0.82^*	93.73±1.18^*
t值		1.068	2.010	2.860	3.756	4.763	4.929	5.263
P值		>0.05	>0.05	>0.05	<0.05	<0.05	<0.05	<0.05

表1 不同浓度二甲基亚砜中24 h、48 h及72 h细胞存活率的比较(±s)

项目	0	0.0025%DMSO	0.005%DMSO	0.01%DMSO	0.02%DMSO	0.04%DMSO	0.08%DMSO	0.16%DMSO
24 h OD值	0.415±0.011	0.412±0.108	0.409±0.011	0.406±0.012	0.403±0.012	0.398±0.013	0.395±0.014	0.389±0.012
存活率(%)	100.00±2.61	98.92±0.48	98.05±0.55	97.18±0.53	95.98±0.61	94.57±0.83^*	93.59±1.17^*	91.43±1.47^*
t值		0.704	1.266	1.836	2.598	3.436	3.882	4.960
P值		>0.05	>0.05	>0.05	>0.05	<0.05	<0.05	<0.05
48 h OD值	0.477±0.016	0.474±0.015	0.470±0.016	0.467±0.015	0.464±0.015	0.461±0.014	0.456±0.014	0.452±0.013
存活率(%)	100.00±3.25	99.10±0.12	98.11±0.07	97.30±0.20	96.50±0.45	95.60±0.54	94.43±0.38^*	93.16±0.66^*
t值		0.479	1.009	1.436	1.851	2.315	2.953	3.573
P值		>0.05	>0.05	>0.05	>0.05	>0.05	<0.05	<0.05
72 h OD值	0.615±0.010	0.610±0.010	0.605±0.010	0.601±0.015	0.596±0.010	0.591±0.009	0.588±0.010	0.583±0.012
存活率(%)	100.00±1.69	98.96±0.08	98.04±0.06	97.19±0.19	96.28±0.29^*	95.30±0.25^*	94.65±0.82^*	93.73±1.18^*
t值		1.068	2.010	2.860	3.756	4.763	4.929	5.263
P值		>0.05	>0.05	>0.05	<0.05	<0.05	<0.05	<0.05

图4 倒置光学显微镜下人角膜上皮细胞在不同浓度柚皮素各时间段内划痕愈合后的形态(100×)　4A~4D分别示实验初始时人角膜上皮细胞在柚皮素0、100 μM、200 μM及400 μM浓度下的形态；4E~4K分别示划痕6 h后人角膜上皮细胞在柚皮素0、100 μM、200 μM及400 μM浓度下的愈合后形态；4L~4O分别示划痕12 h后人角膜上皮细胞在柚皮素0、100 μM、200 μM及400 μM浓度下的愈合后形态；4P~4S分别示划痕24 h后人角膜上皮细胞在柚皮素0、100 μM、200 μM及400 μM浓度下的愈合后形态

表2 不同浓度柚皮素溶液中24 h、48 h及72 h细胞存活率的比较(±s)

项目	0	25 μM Nar	50 μM Nar	100 μM Nar	200 μM Nar	400 μM Nar	800 μM Nar	1600 μM Nar
24 h OD值	0.416±0.006	0.393±0.011	0.378±0.016	0.358±0.011	0.355±0.013	0.297±0.020	0.276±0.013	0.164±0.016
存活率(%)	100.00±1.47	92.81±2.27^a	88.02±3.22^a	82.03±2.03^a	81.11±2.77^a	62.69±3.82^a	56.03±3.95^a	20.87±1.30^a
t值		4.596	5.86	12.421	10.421	15.775	18.058	69.858
P值		<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05
48 h OD值	0.461±0.008	0.439±0.005	0.404±0.007	0.401±0.006	0.320±0.007	0.275±0.006	0.210±0.005	0.167±0.005
存活率(%)	100.00±0.49	93.78±1.01^a	83.99±3.31^a	83.14±3.07^a	60.17±0.46^ab	47.55±0.91^ab	29.19±1.25^ab	17.04±2.00^a
t值		9.628	8.28	9.397	102.698	88.208	91.503	69.768
P值		<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05
72 h OD值	0.638±0.030	0.584±0.029	0.568±0.023	0.540±0.030	0.434±0.006	0.287±0.042	0.245±0.019	0.201±0.012
存活率(%)	100.00±1.90	89.41±1.38^ac	86.35±1.53^a	80.81±0.27^a	60.02±6.20^ab	31.20±1.96^abc	22.96±2.69^abc	14.40±4.02^a
t值		7.813	9.765	17.307	10.673	43.648	40.463	33.348
P值		<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05

表2 不同浓度柚皮素溶液中24 h、48 h及72 h细胞存活率的比较(±s)

项目	0	25 μM Nar	50 μM Nar	100 μM Nar	200 μM Nar	400 μM Nar	800 μM Nar	1600 μM Nar
24 h OD值	0.416±0.006	0.393±0.011	0.378±0.016	0.358±0.011	0.355±0.013	0.297±0.020	0.276±0.013	0.164±0.016
存活率(%)	100.00±1.47	92.81±2.27^a	88.02±3.22^a	82.03±2.03^a	81.11±2.77^a	62.69±3.82^a	56.03±3.95^a	20.87±1.30^a
t值		4.596	5.86	12.421	10.421	15.775	18.058	69.858
P值		<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05
48 h OD值	0.461±0.008	0.439±0.005	0.404±0.007	0.401±0.006	0.320±0.007	0.275±0.006	0.210±0.005	0.167±0.005
存活率(%)	100.00±0.49	93.78±1.01^a	83.99±3.31^a	83.14±3.07^a	60.17±0.46^ab	47.55±0.91^ab	29.19±1.25^ab	17.04±2.00^a
t值		9.628	8.28	9.397	102.698	88.208	91.503	69.768
P值		<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05
72 h OD值	0.638±0.030	0.584±0.029	0.568±0.023	0.540±0.030	0.434±0.006	0.287±0.042	0.245±0.019	0.201±0.012
存活率(%)	100.00±1.90	89.41±1.38^ac	86.35±1.53^a	80.81±0.27^a	60.02±6.20^ab	31.20±1.96^abc	22.96±2.69^abc	14.40±4.02^a
t值		7.813	9.765	17.307	10.673	43.648	40.463	33.348
P值		<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05

[1]	王元，曾凯宏，邓波，等. 柚皮素对高糖模型MIN6细胞的增殖和胰岛素分泌的影响[J]. 重庆医学，2020，49(17): 2844-2848.
[2]	Shi R, Su WW, Zhu ZT, et al. Regulation effects of naringin on diesel particulate matter-induced abnormal airway surface liquid secretion[J]. Phytomedicine, 2019, 63: 153004.
[3]	Lou C, Zhang F, Yang M, et al. Naringenin decreases invasiveness and metastasis by inhibiting TGF-β-induced epithelial to mesenchymal transition in pancreatic cancer cells[J]. PLoS One, 2012, 7(12): e50956.
[4]	曾文峰，张发云，杜刚军，等. 柚皮素：新一代免疫调节剂[J]. 生物化学与生物物理进展，2018，45(9): 915-925.
[5]	Lin J, Sun J, Wang Y, et al. Ocular pharmacokinetics of naringenin eye drops following topical administration to rabbits[J]. J Ocul Pharmacol Ther, 2015, 31(1): 51-56.
[6]	魏爽，盛敏杰，姜亚萍，等. 药物毒性角膜病变的研究进展[J]. 眼科新进展，2019，39(10): 988-991.
[7]	Duda-Madej A, Kozowska J, Krzyžek P, et al. Antimicrobial O-Alkyl derivatives of naringenin and their oximes against multidrug-resistant bacteria[J]. Molecules, 2020, 25(16): 3642.
[8]	张晓燕，张慧芝，陈梦平，等. 某院2013—2016年抗菌药物眼用制剂使用量与眼部感染细菌耐药性分析[J]. 中国药房，2017，28(26): 3634-3638.
[9]	Lin Y, Tan D, Kan Q, et al. The protective effect of naringenin on airway remodeling after mycoplasma pneumoniae infection by inhibiting autophagy-mediated lung inflammation and fibrosis[J]. Mediators Inflamm, 2018: 8753894.
[10]	Zhang C, Zeng W, Yao Y, et al. Naringenin ameliorates radiation-induced lung injury by lowering IL-1β level[J]. J Pharmacol Exp Ther, 2018, 366(2): 341-348.
[11]	Manchope MF, Artero NA, Fattori V, et al. Naringenin mitigates titanium dioxide (TiO₂)-induced chronic arthritis in mice: role of oxidative stress, cytokines, and NFκB[J]. Inflamm Res, 2018, 67(11-12): 997-1012.
[12]	Lather A, Sharma S, Khatkar A. Naringenin derivatives as glucosamine-6-phosphate synthase inhibitors: synthesis, antioxidants, antimicrobial, preservative efficacy, molecular docking and in silico ADMET analysis[J]. BMC Chem, 2020, 14(1): 41.
[13]	Huang YF, Bai C, He F, et al. Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19)[J]. Pharmacol Res, 2020, 158: 104939.
[14]	曲明俐，段豪云，王瑶，等. 三种常用非甾体类抗炎滴眼液对人角膜上皮细胞的毒性研究[J]．中华实验眼科杂志，2015，33(7): 627-632.
[15]	魏会宇，赵少贞. 溴芬酸钠滴眼液对角膜上皮细胞的毒性研究及分析[J]. 中国地方病防治杂志，2016，31(8): 959-960.
[16]	Ayaki M. Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells[J]. Clinical Ophthalmology, 2010, 21(4): 1217-1222.
[17]	贺兵，谢晓燕，张枫，等. 不同浓度二甲基亚砜对兔软骨细胞生长的影响[J/CD]. 中华临床医师杂志：电子版，2014，8(9): 79-82.
[18]	Nirogi R, Kandikere V, Bhyrapuneni G, et al. Effect of dimethyl sulfoxide on in vitro cytochrome P4501A2 mediated phenacetin O-deethylation in human liver microsomes[J]. Drug Metab Dispos, 2011, 39 (11): 2162-2164.
[19]	Nishimura M, Ueda N, Naito S. Effects of dimethyl sulfoxide on the gene induction of cytochrome P450 isoforms, UGT-dependent glucuronosyl transferase isoforms, and ABCB1 in primary culture of human hepatocytes[J]. Biol Pharm Bull, 2003, 26(7): 1052-1056.
[20]	刘耳，王金兵. 细胞冻存保护剂二甲基亚砜的细胞毒作用[J]. 中国预防兽医学报，1994，12(4): 50-52.
[21]	杨莉，安益国，郑建忠. 柚皮素诱导肺腺癌A549细胞凋亡的研究[J]. 中国现代医药杂志，2014，16(10): 19-21.
[22]	周跃，周燕红. 柚皮素联合5-FU对大肠癌细胞增殖和迁移的影响[J]. 湖北科技学院学报(医学版)，2020，34(5): 369-372，394.
[23]	夏一萍. 环孢素A在角膜上皮细胞抗真菌免疫中对Dectin-1表达的影响及机制[D]. 青岛：青岛大学，2017.
[24]	周洋，陈婷妍，美丽巴努·玉素甫. 金雀异黄素通过ROS-NLRP3-IL-1β途径保护角膜上皮细胞免受高渗刺激诱导的损伤[J]. 医学研究杂志，2020，49(4): 80-86.
[25]	Ortiz-Andrade RR, Sánchez-Salgado JC, Navarrete-Vázquez G, et al. Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra- pancreatic glucose regulation[J]. Diabetes Obes Metab, 2008, 10(11): 1097-1104.
[26]	李雪弟. 角膜外伤所致真菌性角膜炎误诊原因分析[J]. 中华眼外伤职业眼病杂志，1999，21(4): 358.
[27]	Chen YY, Chang YM, Wang KY, et al. Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms[J]. Environ Toxicol, 2019, 34(3): 233-239.
[28]	李林芳，杨倩，张源源，等. 柚皮素对人与小鼠乳腺癌细胞的增殖、迁移、侵袭及凋亡的影响[J]．中国普通外科杂志，2020，29(11): 1346-1356.
[29]	Zhao ZJ, Jin GG, Ge YH, et al. Naringenin inhibits migration of breast cancer cells via inflammatory and apoptosis cell signaling pathways[J]. Inflammopharmacology, 2019, 27(5): 1021-1036.
[30]	Wang H, He Y, Hou Y, et al. Novel self-nanomicellizing formulation based on Rebaudioside A: A potential nanoplatform for oral delivery of naringenin[J]. Mater Sci Eng C Mater Biol Appl, 2020, 112: 110926.
[31]	裴岩岩，闫春生，牛美兰，等. 柚皮素纳米混悬剂的制备及其体内药动学行为[J]．中成药，2019，41(9): 2034-2038.
[32]	王建筑，毕研平，李菲，等. 载柚皮素的牛血清白蛋白修饰PLGA纳米粒的制备[J]．中成药，2019，41(11): 2566-2571.
[33]	王晓晨，陈莹，刘丁铭，等．柚皮素脂质体的制备及体外释放度的研究[J]. 泰山医学院学报，2018, 39(4): 371-373.
[34]	Sandhu PS, Kumar R, Beg S, et al. Natural lipids enriched self-nano-emulsifying systems for effective co-delivery of tamoxifen and naringenin: Systematic approach for improved breast cancer therapeutics[J]. Nanomedicine, 2017, 13(5): 1703-1713.

[1]	作者. 脓毒症与脓毒性休克[J]. 中华危重症医学杂志(电子版), 2023, 16(03): 0-.
[2]	龚利缘, 应利君, 吕铁, 李川吉. 平均动脉压对不同乳酸清除率脓毒性休克患者预后的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(01): 37-42.
[3]	林乐清, 曹伟, 唐泽文, 王白永, 王磊, 张宁, 唐文学. 脓毒性休克患者液体复苏时外周灌注指数的临床指导价值研究[J]. 中华危重症医学杂志(电子版), 2022, 15(06): 460-465.
[4]	方辉, 郑武田, 范晓鋆, 刘梦莹. 连花清瘟颗粒联合帕拉米韦对儿童病毒性急性上呼吸道感染的疗效及免疫功能影响[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 350-356.
[5]	江泽莹, 王安婷, 王姣丽, 陈慈, 周秋玲, 黄燕娟, 周芳, 薛琰, 周剑烽, 谭文勇, 杜美芳. 多种植物油组分预防肿瘤放化疗相关毒性反应的效果分析[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 523-527.
[6]	徐双云, 汪佩林, 卫志文. 轮状病毒阳性肠炎并发惊厥危险因素及相关预测模型构建[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(04): 260-266.
[7]	张凯玄, 梁燕, 石红妍, 郑煦暘, 连建奇, 张欠欠. 出血热病毒感染呼吸道研究进展[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(01): 12-15.
[8]	唐芹芳, 孙明忠, 傅庆萍, 肖丽华, 颜冬梅, 王颖, 季宏建. 糖尿病患者索氏梭菌感染致中毒性休克综合征一例[J]. 中华实验和临床感染病杂志(电子版), 2022, 16(05): 354-358.
[9]	张依, 许东梅. 四例首诊误诊为肿瘤的神经梅毒树胶样肿病例[J]. 中华实验和临床感染病杂志(电子版), 2022, 16(04): 280-286.
[10]	肖慧, 徐维国, 范小兵, 李厚衡. 血清IL-34、SP-D、CXCL17在甲型流感病毒性肺炎患者中表达及临床意义[J]. 中华肺部疾病杂志(电子版), 2023, 16(03): 349-351.
[11]	王璐, 黄楚月, 李志利, 王一, 孔德松, 刘飞, 樊志敏. 患者来源的结直肠癌类器官模型的构建及其在有毒中药抗癌活性评价中的应用[J]. 中华结直肠疾病电子杂志, 2022, 11(04): 343-348.
[12]	卢贤红, 钱石陆, 周敏. 微生态调节剂对小儿轮状病毒性肠炎的临床干预效果分析[J]. 中华消化病与影像杂志(电子版), 2023, 13(04): 245-249.
[13]	孔凡彪, 杨建荣. 肝脏基础疾病与结直肠癌肝转移之间关系的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(07): 818-822.
[14]	李秋琼, 薛静, 王敏, 陈芬, 肖美芳. NSE、SIL-2R、TNF-α检测对小儿病毒性脑膜炎与细菌性脑膜炎的诊断价值[J]. 中华临床医师杂志(电子版), 2023, 17(03): 303-307.
[15]	于晓倩, 徐瑞, 黄文, 吴霞, 赵学强, 郑飞, 李欣然. 病毒性心肌炎向扩张型心肌病转变进展的诊断学特征[J]. 中华诊断学电子杂志, 2022, 10(04): 238-242.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

The toxicity of naringenin to human corneal epithelial cells

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

The toxicity of naringenin to human corneal epithelial cells