Intervention and Mechanism of Dexmedetomidine on A549 Cells Injured by Hypoxia/Reoxygenation

  • Hui Gao Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
  • Ziyin Luo Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
  • Zhuolin Zhou Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
  • Yiming Wu Division of Cardiovascular Medicine University of Iowa Carver College of Medicine Iowa City, American 50309
  • Wantie Wang Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
DOI https://doi.org/10.22270/jddt.v9i3.2607

Abstract

Objective: To investigate the effect and mechanism of dexmedetomidine (DEX) on hypoxia /reoxygenation (H/R) injury of A549 cells.


Methods: A549 cells were cultured and randomly divided into four groups (n=10): Normoxic group;DEX group; H/R injury group;H/R injury+DEX intervention group. Observe the morphological changes of cells; Cell viability was detected by cck-8 assay. TUNEL assay was used to detect apoptosis index (AI).Expressions of GRP78, CHOP, JNK, caspase-12, caspase-3 proteins and mRNA were detected by Western Blot and RT-PCR;Detect the activity of caspase-3.


Results: Compared with the H group, the OD value and AI value in the HD group were significantly up-regulated, apoptotic cells were significantly decreased, the expressions of CHOP, caspase-12, p-JNK and caspase-3 proteins and mRNA were significantly decreased, the GRP78 protein and mRNA increased, and the caspase-3 activity was significantly decreased, the differences were statistically significant (P<0.01).


Conclusion: Dexmedetomidine has a protective effect on A549 cells after H/R injury, which may be related to its inhibition of apoptosis induced by excessive endoplasmic reticulm stress.


Keywords: Dexmedetomidine; Hypoxia/Reoxygenationinjury;Apoptosis;Endoplasmicreticulm stress.

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Author Biographies

Hui Gao, Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Ziyin Luo, Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Zhuolin Zhou, Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Yiming Wu, Division of Cardiovascular Medicine University of Iowa Carver College of Medicine Iowa City, American 50309

Division of Cardiovascular Medicine University of Iowa Carver College of Medicine Iowa City, American 50309

Wantie Wang, Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

Ischemia/Reperfusion Injury Research Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

References

1. Junhui Zhou, Liangrong Wang, Maolin Hao. Effects of small interfering RNA on apoptosis and CCAAT / enhancer binding protein homologous protein in lung ischemia / reperfusion injury in mice. Chinese Journal of Experimental Surgery. 2013; 30:1608-11.
2. Maolin HAO, Shan ZHAO, Haie CHEN. Effect of JNK gene on lung injury induced by ischemic reperfusion in siRNA under over expressing endoplasmic reticulum. Chinese Journal of Applied Physiology.2014; 30:5-10.
3. Junhui Zhou, Dan Chen, Haie Chen. Effects of caspase-12-siRNA pretreatment on lung ischemia-reperfusion injury in mice. Chinese Journal of Anesthesiology. 2014; 34:105-107.
4. Kucuk A, Yaylak F, Cavunt-Bayraktar A. The protective effects of dexmedetomidine on hepatic ischemia reperfusion injury.Bratisl Lek Listy. 2014; 15: 680-684.
5. Guo Changman, Chen Dan, Song Dong. Protective effects of dexmedetomidine on lung ischemia-reperfusion injury in mice. Chinese Journal of Clinical Pharmacology and Therapeutics.2016; 21:145 -149.
6. Chen Dan, Song Dong, Ye Yuzhu. Deemethamidine by affecting the CHOP apoptotic pathway to reduce ischemia / reperfusion lung injury. Chinese Journal of Pathophysiology.2015; 31:1093-98 .
7. Jian Cui, Hailin Zhao, Chunyan Wang. Dexmedetomidine attenuates oxidative stress induced lung alveolar epithelial cell apoptosis in vitro. Oxidative Medicine and Cellular Longevity. 2015; 2015:1-11
8. Chenfang Luo, Dongdong Yuan, Weifeng Yao. Dexmedetomidine protects against apoptosis induced by hypoxia/reoxygenation through the inhibition of gap junctions in NRK-52E cells. Life Sciences .2015; 122:72-77.
9. Wang Wang, Lingyun Jia, Tengke Wang. Endogenous calcitonin gene-related peptide protects human alveolar epithelial cells through protein kinase C and heat shock protein. J Biol Chem .2005; 280:20325-30.
10. Lingyun Jia, Mingjiang Xu, Wei Zhen. Novel anti-oxidative role of calreticulin in protecting A549 human type II alveolar epithelial cells against hypoxic injury. Am J Physiol Cell Physiol. 2008; 294:47-55.
11. Kim MH, Aydemir TB, Cousins RJ. Dietary zinc regulates apoptosis through the p-elF2α/ATF4/CHOP Pathway during Pharmacologically Induced Endoplasmic Reticulum Stress in Livers of Mice.J Nutr .2016; 146:2180-86.
12. Lakshmanan AP, Thandavarayan RA, Palaniyandi SS. Modulation of AT-1R/ CHOP-JNK-Caspase12 pathway by olmesartan treatment attenuates ER stress-induced renal apoptosis in streptozotocin-induced diabetic mice. Eur J Pharm Sci.2011; 44:627-634.
13. Xu J, Qin X, Cai X. Mitochondrial JNK activation triggers autophagy and apoptosis and aggravates myocardial injury following ischemia/reperfusion. Biochim Biophys Acta.2015; 1852:262-270.
14. Zhang XY, Zhang TT, Song DD. Endoplasmic reticulum chaperone GRP78 is involved in autophagy activation induced by ischemic preconditioning in neural cells . Mol Brain 2015;. 8:20.
15. Jiang YX, Dai ZL, Zhang XP. Dexmedetomidine alleviates pulmonary edema by upregulating AQP1 and AQP5 expression in rats with acute lung injury induced by lipopolysaccharide. Huazhong Univ Sci Technolog Med Sci.2015; 35:684 -688.
16. Cui J, Zhao H, Yi B,et al. Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo.Crit Care Med. 2015; 43:356-368.
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How to Cite
1.
Gao H, Luo Z, Zhou Z, Wu Y, Wang W. Intervention and Mechanism of Dexmedetomidine on A549 Cells Injured by Hypoxia/Reoxygenation. JDDT [Internet]. 15May2019 [cited 28Feb.2020];9(3):99-06. Available from: http://jddtonline.info/index.php/jddt/article/view/2607
Issue
Vol 9 No 3 (2019): Volume 9, Issue 3, May-June 2019
Section
Research
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