槲皮素通过抑制丝裂原活化蛋白激酶信号通路表达减轻小鼠放射性肺炎

doi:10.6040/j.issn.1671-7554.0.2019.091

摘要/Abstract

摘要： 目的建立放射性肺炎小鼠模型,应用槲皮素对其干预,观察槲皮素对小鼠放射性肺炎的疗效。方法随机数字表法将80只BALB/c小鼠分为6组:健康对照组(n=8)、单纯给药组(n=8)、单纯照射组(n=16)、照射+阿米福汀组(n=16)、照射+槲皮素(4 mg/mL)组(n=16)、照射+槲皮素(2 mg/mL)组(n=16)。以6 mV X射线全肺单次10 Gy照射,各槲皮素给药组尾静脉注射不同浓度槲皮素(2、4 mg/mL),单纯给药组注射槲皮素4 mg/mL,健康对照组、单纯照射组注射4 mg/mL生理盐水,照射+阿米福汀组注射4 mg/mL阿米福汀。照射后1~8周,每周取各组小鼠双侧肺组织,HE染色观察小鼠肺组织炎性病理变化;采用免疫组织化学法和Western blotting技术观察槲皮素对丝裂原活化蛋白激酶(MAPK)标志蛋白p38、SAPK/JNK和p44/p42表达的影响。结果与单纯照射组比较,各照射+槲皮素组小鼠的肺组织炎性表现减轻(P<0.01),肺组织p38、SAPK/JNK和p44/p42染色阳性程度、蛋白表达均降低(P<0.01)。结论槲皮素通过遏抑MAPK标志蛋白p38、SAPK/JNK、p44/p42的表达,从而阻止炎性因子的释放,最终降低了组织损伤和炎症程度。

关键词: 槲皮素, 放射性肺炎, 丝裂原活化蛋白激酶

Abstract: Objective To establish the mice model of radiation-induced lung injury, and to study the curative effect of quercetin on it. Methods Eighty BALB/c mice were randomly assigned to 6 groups and treated as follows: mice in normal control group(n=8)were intravenously injected with 4 mg/mL saline; mice in quercetin group(n=8)were intravenously injected with 4 mg/mL quercetin; mice in simply irradiated group(n=16)received a single 10 Gy dose of radiation; mice in quercetin(4 mg/mL)intervention group received a single 10 Gy dose of radiation and were intravenously injected with 4 mg/mL quercetin; mice in quercetin(2 mg/mL)intervention group received a single 10 Gy dose of radiation and were intravenously injected with 2 mg/mL quercetin; mice in amifostine intervention group received a single 10 Gy dose of radiation and were intravenously injected with 4 mg/mL amifostine. From week 1 to week 8 after irradiation, lung tissues in both sides of mice were harvested for further experiments. The expressions of marker proteins of mitogen-activated protein kinase(MAPK), p38, SAPK/JNK and p44/p42, were assayed by immunohistochemistry and Western blotting. Results Compared with the simply irradiated group, the quercetin(4 mg/mL)intervention group and quercetin(2 mg/mL)intervention group showed the alleviative inflammation, the decreased positive gradings and expressions of p38, SAPK/JNK and p44/p42 proteins in lung tissues. Conclusion Quercetin signifi- 山东大学学报 (医学版)57卷5期 -程健,等.槲皮素通过抑制丝裂原活化蛋白激酶信号通路表达减轻小鼠放射性肺炎 \=-cantly attenuates radiation-induced lungs injury in mice, which may be associated with the inhibition of MAPK signal pathway.

Key words: Quercetin, Radiation-induced lung injury, Mitogen-activated protein kinase

中图分类号:

R73-34

程健,姜玉华. 槲皮素通过抑制丝裂原活化蛋白激酶信号通路表达减轻小鼠放射性肺炎[J]. 山东大学学报 (医学版), 2019, 57(5): 87-92.

CHENG Jian, JIANG Yuhua. Protective effect of quercetin on radiation-induced lungs injury in mice via inhibition of mitogen-activated protein kinase signal pathway[J]. Journal of Shandong University (Health Sciences), 2019, 57(5): 87-92.

参考文献

[1] 岳海英,王仁生.放射性肺损伤机制研究进展[J].中华放射肿瘤学杂志, 2014, 23(3): 230-233.
[2] 徐颖臻,张秀丽,张如意.p38MAPK-HSP27通路在右美托咪定减轻小鼠内毒性急性肺损伤中的作用[J].中华麻醉学杂志, 2015, 35(3): 366-369. XU Yingzhen, ZHANG Xiuli, ZHANG Ruyi, et al. Role of p38MAPK-HSP27 signaling pathway in attenuation of LPS-induced acute lung injury by dexmedetomidine in mice [J]. Chin J Anesthesiol, 2015, 35(3): 366-369.
[3] Angst E, Park JL, Moro A, et al. The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo[J]. Pancreas, 2013, 42(2): 223-229.
[4] 陈曦, 赵路军, 徐利明, 等. 氧化应激在放射性肺损伤中的相关研究进展[J]. 中华放射医学与防护杂志, 2016, 36(4): 312-315. CHEN Xi, ZHAO Lujun, XU Liming, et al. Research progress of oxidative stress in radiation-induced lung injury[J]. Chinese Journal of Radiological Medicine and Protection, 2016, 36(4): 312-315.
[5] Antonic V, Rabbani ZN, Jackson IL, et al. Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury[J]. Free Radic Res, 2015, 49(10): 1259-1268.
[6] 郑苗丽,冯勤付.放射性肺损伤的研究进展[J].中华放射肿瘤学杂志, 2018, 27(7): 692-695. ZHENG Miaoli, FENG Qinfu. Research progress in radiation-induced lung injury [J]. Chin J Radiat Oncol, 2018, 27(7): 692-695.
[7] 宣伟, 李帅, 吴秀艳, 等. 萝卜硫素对小鼠放射性肺损伤的防护作用机制[J]. 中华放射医学与防护杂志, 2017, 37(4): 251-258. XUAN Wei, LI Shuai, WU Xiuyan, et al. Mechanism of protective effect of sulforaphane against radiation-induced lung injury in mice[J]. Chinese Journal of Radiological Medicine and Protection, 2017, 37(4): 251-258.
[8] Lierova A, Jelicova M, Nemcova M, et al. Cytokines and radiation-induced pulmonary injuries[J]. J Radiat Res, 2018, 59(6): 709-753.
[9] Jang SS, Kim HG, Han JM, et al. Modulation of radiation-induced alterations in oxidative stress and cytokine expression in lung tissue by Panax ginseng extract[J]. Phytother Res, 2015, 29(2): 201-209.
[10] Sui X, Kong N, Ye L, et al. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents[J]. Cancer Lett. 2014, 344(2): 174-179.
[11] Luo F, Shi J, Shi Q, et al. ERK and p38 upregulation versus bcl-6 downregulation in rat kidney epithelial cells exposed to prolonged hypoxia[J]. Cell Transplant, 2017, 26(8): 1441-1451.
[12] 胡晓, 王煜, 沈海涛, 等. GW3965抑制p38丝裂原活化蛋白激酶信号通路表达减轻百草枯致小鼠急性肺损伤[J]. 中华急诊医学杂志, 2018, 27(5): 507-512. HU Xiao, WANG Yu, SHEN Haitao, et al. Protective effect of GW3965 on PQ-induced acute lung injury in mice via inhibition of p38MAPK signal pathway[J]. Chinese Journal of Emergency Medicine, 2018, 27(5): 507-512.
[13] Chorzalska A, Ahsan N, Rao RSP, et al. Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of chronic myeloid leukemia[J]. Mol Oncol, 2018, 12(5): 630-647.
[14] Choi M, Schreiber A, Eulenberg-Gustavus C, et al. Endothelial NF-κB blockade abrogates ANCA-induced GN[J]. JASN, 2017, 28(11): 3191-3204.
[15] Wang S, Gu J, Xu Z, et al. Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway[J]. J Cell Mol Med, 2017, 21(6): 1182-1192.
[16] Chen L, Jiang K, Chen H, et al. Deguelin induces apoptosis in colorectal cancer cells by activating the p38 MAPK pathway[J]. Cancer Manag Res, 2019, 11: 95-105. doi:10.2147/CMAR.S169476.
[17] Zhang MY, Yan ZB, Bu LL, et al. Rapeseed protein-derived antioxidant peptide RAP alleviates renal fibrosis through MAPK/NF-κB signaling pathways in diabetic nephropathy[J]. Drug Des Devel Ther, 2018, 12: 1255-1268. doi:10.2147/DDDT.S162288.
[18] Cai W, Yu D, Fan J, et al. Quercetin inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells via the Smad pathway[J]. Drug Des Devel Ther, 2018, 12: 4149-4161. doi:10.2147/dddt.s185618.
[19] Tian H, Liu Q, Qin S, et al. Synthesis and cardiovascular protective effects of quercetin 7-O-sialic acid[J]. J Cell Mol Med, 2017, 21(1): 107-120.
[20] Sangai NP, Patel CN, Pandya HA. Ameliorative effects of quercetin against bisphenol A-caused oxidative stress in human erythrocytes: an in vitro and in silico study[J]. Toxicol Res(Camb), 2018, 7(6): 1091-1099.
[21] Abdelhalim MAK, Qaid HA, Al-Mohy Y, et al. Effects of quercetin and arginine on the nephrotoxicity and lipid peroxidation induced by gold nanoparticles in vivo[J]. Int J Nanomedicine, 2018, 13: 7765-7770. doi:10.2147/IJN.S183281.
[22] Kobori M, Takahashi Y, Sakurai M, et al. Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in adipose tissue of diet-induced obese mice[J]. Mol Nutr Food Res, 2016, 60(2): 300-312.
[23] Zhao L, Cen F, Tian F, et al. Combination treatment with quercetin and resveratrol attenuates high fat diet-induced obesity and associated inflammation in rats via the AMPKα1/SIRT1 signaling pathway[J]. Exp Ther Med, 2017, 14(6): 5942-5948.
[24] Zhao L, Zhang Q, Ma W, et al. A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota[J]. Food Funct, 2017, 8(12): 4644-4656.
[25] Peng Z, Gong X, Yang Y, et al. Hepatoprotective effect of quercetin against LPS/d-GalN induced acute liver injury in mice by inhibiting the IKK/NF-κB and MAPK signal pathways[J]. Int Immunopharmacol, 2017, 52: 281-289. doi:10.1016/j.intimp.2017.09.022.

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