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Experimental study of the effects of AMP-dependent protein kinase metformin on emphysema in aged rats |
Received:May 27, 2019 |
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DOI:10.11915/j.issn.1671-5403.2019.11.180 |
Key words:pulmonary emphysema lung damage AMP-dependent protein kinase inflammation Corresponding author:DENG Hai-Bo, E-mail:ho393g@163.com〖FL |
Author Name | Affiliation | E-mail | DENG Hai-Bo | Department of Respiratory Medicine, Jianyang People′s Hospital of Sichuan Province, Jianyang 641400, China | ho393g@163.comexperimental | LONG Miao | Department of Respiratory Medicine, Jianyang People′s Hospital of Sichuan Province, Jianyang 641400, China | ho393g@163.comexperimental | JIA Kun-Lin | Department of Respiratory Medicine, Jianyang People′s Hospital of Sichuan Province, Jianyang 641400, China | ho393g@163.comexperimental | YU Lin | Department of Respiratory Medicine and Critical Care, First Affiliated Hospital of Chengdu Medical College, Chengdu 610081, China | ho393g@163.comexperimental |
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Abstract: |
Objective To investigate the effects of AMP-dependent protein kinase (AMPK) metformin on emphysema in the aged rats. Methods Forty 24-month-old SD rats with a body mass of (233.00±12.00)g were selected and were randomized into control group, model group, dexamethasone group and joint intervention group, with 10 rats in each group. Except for the control group, the other three groups were treated with smoking combined with intratracheal drip of porcine tryptoelastase to establish animal models of emphysema. Intraperitoneally, the control group and the model group were then routinely perfused with 5ml saline once a day, the dexamethasone group with an equal volume of 2mg/kg dexamethasone once a day, and the joint intervention group with an equal volume of 250mg/kg AMPK metformin plus 2mg/kg dexamethasone. All four groups were continuously intervened for 14 days. Lung damage in the four groups was observed using HE staining. They were compared in the respects of the levels of inflammatory factors[tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6) and IL-8] and biochemical indices (white blood cell count, neutrophil and lymphocyte ratio). SPSS statistics 18.0 was employed for data analysis. Depending on data type, intergroup comparison was performed using analysis of variance or pairwise comparison. Results No abnormality was observed in HE staining in the control group. In the model group, the respiratory bronchi and alveoli were of different sizes, the number of alveoli decreased significantly, alveolar septum became thinner, and some alveolar septa ruptured leading to emphysema-like changes such as alveolar fusion. In the dexamethasone group, the number of alveoli decreased slightly, a few ruptures of alveolar septa were observed with emphysema-like changes. The joint intervention group showed no significant emphysema-like changes and no significant reduction in alveolar number. TNF-a, IL-6 and IL-8, white blood cell count, neutrophil and lymphocyte ratio were (178.53±19.55)pg/ml, (96.58±0.06)pg/ml,(74.55±5.68)pg/ml, (3.49±0.68)×108/L, (17.35±3.24)% and (12.29±2.45)% respectively in control group; (261.39±23.21)pg/ml, (753.23±43.24)pg/ml, (323.59±17.85)pg/ml, (13.29±1.46)×108/L, (34.69±4.64)% and (43.53±5.77)% in model group; (243.66±18.68)pg/ml, (323.32±25.69)pg/ml, (132.31±10.51)pg/ml, (9.48±1.35)×108/L, (25.69±5.32)% and (32.51±4.34)% in the dexamethasone group; (213.69±15.32)pg/ml, (102.49±7.46)pg/ml, (89.43±6.59)pg/ml, (6.31±1.12)×108/L, (21.59±4.31)% and (21.29±3.45)% in joint intervention group. Compared with the control group, TNF-a, IL-6, IL-8, white blood cell count, neutrophil and lymphocyte ratio increased significantly in the model group and dexamethasone group; compared with the model group, the above parameters decreased significantly in the dexamethasone group and the joint intervention group; compared with the dexamethasone group, the above indices decreased significantly in the joint intervention group, all the differences being statistically significant (P<0.05). Conclusion AMPK metformin is effective for emphysema in the senile rats, reducing the level of inflammatory factors and improving lung damage. |
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