N-乙酰半胱氨酸对PM2.5致大鼠肺损伤时MAPK主要通路蛋白活化及氧化炎症反应的影响

doi:10.24920/003527

Abstract

Objective To evaluate the antagonistic effects of N-acetylcysteine (NAC) on mitogen-activated protein kinases (MAPK) pathway activation, oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter (PM_2.5).Methods Forty eight male Wistar rats were randomly divided into six groups: blank control group (C1), water drip control group (C2), PM_2.5 exposed group (P), low-dose NAC treated and PM_2.5 exposed group (L), middle-dose NAC treated and PM_2.5 exposed group (M), and high-dose NAC treated and PM_2.5 exposed group (H). PM_2.5 suspension (7.5 mg/kg) was administered tracheally once a week for four times. NAC of 125 mg/kg, 250 mg/kg and 500 mg/kg was delivered intragastrically to L, M and H group respectively by gavage (10 ml/kg) for six days before PM_2.5 exposure. The histopathological changes and human mucin 5 subtype AC (MUC5AC) content in lung tissue of rats were evaluated. We investigated IL-6 in serum and bronchoalveolar lavage fluid (BALF) by Enzyme-linked immunosorbent assay (ELISA), MUC5AC in lung tissue homogenate by ELISA, glutathione peroxidase (GSH-PX) in serum and BALF by spectrophotometry, and the expression of p-ERK1/2, p-JNK1/2 and p-p38 proteins by Western blot. All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM_2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells. Rats receiving NAC treatment showed less histological destruction and mucus secretion. Of P, L, M and H group, MUC5AC in lung tissue, IL-6 in serum and BALF were higher than controls (C1 and C2) (all P<0.05), with the highest levels found in the P group and a decreasing trend with increase of NAC dose. The activity of GSH-PX in serum and BALF of PM_2.5 exposed rats (P, L, M and H) was lower than that of controls (all P<0.05), with higher activities found in NAC treated rats (L, M, and H), and an increasing trend with increase of NAC dose. The expressions of p-ERK1/2, p-JNK1/2 and p-p38 proteins in PM_2.5 exposed lung tissue (P, L, M and H) was higher than controls (all P<0.05), with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation, lung oxidative stress and inflammatory injury induced by PM_2.5 in rats.

Key words: fine particulate matter (PM_2.5), N-acetylcysteine, mitogen-activated protein kinases, oxidative stress, inflammatory response, rats

Ping Fen, Cao Qin, Lin Hua, Han Shuzhi. Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation, Oxidative Stress and Inflammatory Responses in Rats with PM_2.5 Induced Lung Injuries[J].Chinese Medical Sciences Journal, 2019, 34(4): 270-276.

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References 22.

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Group	Lung tissue MUC5AC (pg/mg)	Serum		BALF
Group	Lung tissue MUC5AC (pg/mg)	IL-6 (pg/mg)	GSH-PX (U)	IL-6 (pg/ml)	GSH-PX (U)
C1	108.63±9.39	29.50±2.60	4568.56±203.53	41.27±2.24	190.53±2.71
C2	110.54±4.94	30.36±3.49	4531.75±129.02	41.47±2.31	189.46±2.46
P	192.25±13.52^ab	56.20±4.89^ab	1512.11±278.37^ab	71.85±2.44^ab	120.22±1.91^ab
L	171.21±12.58^abc	52.59±4.38^ab	1527.53±145.73^ab	69.63±1.95^ab	125.77±2.93^abc
M	153.06±4.60^abcd	46.43±3.29^abcd	2487.14±247.75^abcd	63.22±2.71^abcd	145.71±2.29^abcd
H	139.04±3.67^abcde	40.40±2.77^abcde	2659.91±197.28^abcd	56.54±1.46^abcde	181.58±1.57^abcde
F value	88.409	72.203	296.754	275.291	1333.633
P value	0.000	0.000	0.000	0.000	0.000

Group	p-ERK1/2	p-JNK1/2	p-p38
C1	0.40±0.02	0.31±0.01	0.20±0.02
C2	0.40±0.02	0.31±0.02	0.20±0.02
P	0.81±0.03^ab	0.82±0.03^ab	0.88±0.04^ab
L	0.75±0.01^abc	0.66±0.01^abc	0.63±0.01^abc
M	0.61±0.02^abcd	0.50±0.02^abcd	0.47±0.01^abcd
H	0.49±0.01^abcde	0.37±0.02^abcde	0.29±0.02^abcde
F value	201.256	333.001	524.187
P value	0.000	0.000	0.000

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Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation, Oxidative Stress and Inflammatory Responses in Rats with PM2.5 Induced Lung Injuries