Effect of particulate matter 2.5 at urban centre of Hangzhou on lung impairment in rats

doi:10.12047/j.cjap.5651.2018.069

Abstract

Abstract: Objective: To explore the effect of ambient particle matter 2.5 (PM2.5) collected in the urban center of Hangzhou on the lung injury of rats and on the activating of endoplasmic reticulum pathway. Methods: PM2.5 samples were collected on quartz fiber filters using a PM2.5 high-volume air sampler in the urban area of Hangzhou. The collected PM2.5 particles were extracted in ultrapure water and concentrated by vacuum freeze-drying. Twenty-four male Sprague-Dawly (SD) rats were randomly divided into 3 groups:saline control group, low dose PM2.5 exposure group (5 mg/kg BW) and high dose PM2.5 exposure groups (25 mg/kg BW). Each group received intratracheal instillation of PM2.5, once a week for 4 weeks. Twenty-four hours after the last exposure, the rats were narcotized and sacrificed, left lung was isolated and fixed with 4% paraformaldehyde for histopathological detection. The bronchoalveolar lavage fluid (BALF) was collected from the right lung. The total antioxidant capacity (T-AOC) level, the activities of superoxide dismutase (SOD) and lactic dehydrogenase (LDH) in BALF were detected by chemical colorimetry. The level of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) cytokines in BALF was measured by enzyme linked immunosorbent assay (ELISA). And the protein expressions of glucose-regulated protein 78 (GRP78), phosphorylated protein kinase receptor-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor (p-eIF2α), transcription factors C/EBP homologue protein (CHOP), inositol-requiring enzyme 1α (IRE1α) and X-box binding protein 1 (XBP1) in lung tissue were determined by Western blotting. Results: Compared with control group, rats in both low dose (5 mg/kg) and high dose (25 mg/kg) PM2.5-treated groups showed obviously dose-dependent pulmonary toxicity including thickening of alveolar walls, narrowing of alveolar space, interstitial hyperplasia and inflammatory cell infiltration. Compared with control group, T-AOC level and the SOD activity in BALF in both PM2.5-treated groups were decreased dose-dependently (P<0.05), whereas the LDH activity in BALF were increased in a dose-dependent manner (P<0.05). Exposure to PM2.5 resulted in a increasing of the release of proinflammatory cytokines including TNF-α, IL-1β and IL-6 in rat lung in a dose-dependent manner (P<0.05). The levels of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α and spliced XBP1 (XBP1-S) were significantly up-regulated, whereas the level of unspliced XBP1 (XBP1-U) was down-regulated in the rat lung tissue of high-dose PM2.5 treated group. Conclusion: The PM2.5 in the urban area of Hangzhou can significantly cause lung inflammatory injury in rats. Both oxidative stress and activation of ER stress pathways may be related to such PM2.5 inhalation-induced lung inflammatory injury.

Key words: ambient particle matter 2.5, rat, lung injury, inflammatory response, oxidative stress, ER stress

TIAN Cheng-yuan, YAN Ming, ZHANG yun, LIU Ke-zhou, GUO Miao, SUN Yong-hong, XUE Ling-yun, ZHU Lei, XU Ying. Effect of particulate matter 2.5 at urban centre of Hangzhou on lung impairment in rats[J]. CJAP, 2018, 34(4): 299-303.

References

[1] 中国环境保护部, 2013年中国环境状况公报[R]. 北京:中国环境保护部, 2014.
[2] Park SK, Wang W. Ambient air pollution and type 2diabe-tes:a systematic review of epidemiologic research[J]. Curr Environ Health Rep, 2014, 1:275-286.
[3] Chalbot MC, Jones TA, Kavouras IG. Trends of non-ac-cidental, cardiovascular, stroke and lung cancer mortality in Arkansas are associated with ambient PM2.5 reduc-tions[J]. Inter J Environ Res Pub Heal, 2014, 11:7442-7455.
[4] Riva DR, Magalhłes CB, Lopes AA, et al. Low dose of fine particulate matter (PM2.5) can induce acute oxida-tive stress, inflammation and pulmonary impairment in healthy mice[J]. Inhal Toxicol, 2011, 23(5):257-267.
[5] Jin Y, Wu W, Zhang W, et al. Involvement of EGF re-ceptor signaling and NLRP12 inflammasome in fine par-ticulate matter-induced lung inflammation in mice[J]. Environ Toxicol, 2017, 32(4):1121-1134.
[6] 洪盛茂, 焦荔, 何曦, 等. 杭州主城区悬浮细颗粒PM2.5浓度变化及其组分分析[J]. 中国粉体技术, 2010, 16(01):14-17, 34.
[7] 黄斌, 邓旺, 王导新. p38丝裂原活化蛋白激酶在大鼠油酸型急性肺损伤中的作用[J]. 中国应用生理学杂志, 2017, 33(4):334-339, 386.
[8] Longhin E, Pezzolato E, Mantecca P, et al. Season linked responses to fine and quasi-ultrafine Milan PM in cultured cells[J]. Toxicol in Vitro, 2013, 27(2):551-559.
[9] Yao H, Sundar IK, Ahmad T, et al. SIRT1 protects a-gainst cigarette smoke-induced lung oxidative stress via a FOXO3-dependent mechanism[J]. Am J Physiol Lung Cell Mol Physiol, 2014, 306(9):816-828.
[10] Rahman I, Mulier B, Gilmour PS, et al. Oxidant-media-ted lung epithelial cell tolerance:the role of intracellular glutathione and nuclear factor-kappa B[J]. Biochem Pharmacol, 2001, 62(6):787-794.
[11] Yang H, Liu C, Yang D, et al. Comparative study of cy-totoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials:the role of particle size, shape and composition[J]. J Appl Toxicol, 2009, 29(1):69-78.
[12] Duranbedolla J, Ma OS, Saldaйanavor V, et al. Sepsis, mitochondrial failure and multiple organ dysfunction[J]. Clin Invest Med, 2014, 37(2):58-69.
[13] 杨锐, 贾强, 刘小粉, 等. 硫化氢对大鼠糖尿病心肌病氧化应激及内质网应激的影响[J]. 中国应用生理学杂志, 2016, 32(1):8-12.
[14] 龙杰, 王羽, 刘晓翠, 等. 氧化应激对原代培养乳鼠心房肌细胞中内质网应激及凋亡因子的影响[J]. 中国应用生理学杂志, 2017, 33(2):185-188.
[15] Malhotra JD, Kaufman RJ. Endoplasmic reticulum stress and oxidative stress:A vicious cycle or a double-edged sword[J]? Antioxid Redox Sign, 2007, 9(12):2277-2293.
[16] Hetz C. The unfolded protein response:controlling cell fate decisions under ER stress and beyond[J]. Nat Revs Molr Cell Biol, 2012, 13(2):89-102.
[17] Kim J, Song H, Heo HR, et al. Cadmium-induced ER stress and inflammation are mediated through C/EBP-DDIT3 signaling in human bronchial epithelial cells[J]. Exp Molr Med, 2017, 49(9):e372-382.
[18] Wang L, Cheng W, Zhang Z. Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibro-sis animal model[J]. Molr Med Rep, 2017, 16(1):310-316.
[19] Zhang K. Integration of ER stress, oxidative stress and the inflammatory response in health and disease[J]. Int J Clin Exp Med, 2010, 3(1):33-40.
[20] Son B, Kwon T, Lee S, et al. CYP2E1 regulates the de-velopment of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms[J]. Am J Phys-iol Lung Cell Mol Physiol, 2017, 313(5):L916-L929.