Anti-apoptosis effect and mechanism of heme oxygenase-1 on lung injury after cardiopulmonary bypass_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SHENG Wei ¹ , WANG Haitao ² , CHI Yifan ¹ ,  SUN Long ¹ , NIU Zhaozhuo ¹ , LIN Mingshan ¹ , QIAO Youjin ¹ , WU Jiantao ¹

1. Department of Cardiovascular Surgery, Qingdao Municipal Hospital, Medical College of Qingdao University, Qingdao, 266071, Shandong, P.R.China;
2. Pharmacy Department, Qingdao Cancer Hospital, Medical College of Qingdao University, Qingdao, 266042, Shandong, P.R.China;

Corresponding author：

SUN Long, Email: sw8011@126.com

Keywords：

Heme oxygenase-1; cardiopulmonary bypass; lung injury; cell apoptosis

DOI：

10.7507/1007-4848.201610033

Video：

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Objective To determine the anti-apoptosis effects of heme oxygenase-1 (HO-1) on lung injury after cardiopulmonary bypass (CPB), and to investigate its probable mechanisms. Methods A total of 144 male Wistar rats with wight of 250-350 g were divided into 3 groups: group A (control group), group B (cobalt protoporphyrin, CoPP), and group C [CoPP and zinc protoporphyrin (ZnPP)] randomly. A modified rat model of CPB-induced lung injury was established. And then the lung tissues were taken at different times for the relevant indicators test: before CPB (T0), immediately after CPB (T1), 2 h after CPB (T2), 6 h after CPB (T3), 12 h after CPB (T4), and 24 h after CPB (T5). The expression of HO-1 and Bcl-2 protein in each group was tested by immunohistochemistry, and cell apoptosis by TUNEL. Results The HO-1 protein expression in group B was significantly higher than that in groups A and C at any given time point, so was the HO-1 activity (P<0.05). There was no significant difference in Bcl-2 expression of lung tissue before CPB among each group (P>0.05). The Bcl-2 protein reduced gradually after CPB. The expressions of Bcl-2 protein in group B at all time points after bypass were significantly higher than that in groups A and C (P<0.05). The apoptosis index (AI) showed no significant difference before CPB in each group (P>0.05), and increased gradually after CPB. AI in group B at any time point after bypass was lower than that in groups A and C (P<0.05). The HE staining results showed that the damage of lung tissue in group B obviously reduced compared with groups A and C. Conclusion CoPP can induce a large amount of HO-1 expression in the lung tissue, and it is still highly expressed after CPB. So it plays an important role in anti-apoptosis through the up-regulation of Bcl-2 protein expression.

Citation： SHENG Wei, WANG Haitao, CHI Yifan, SUN Long, NIU Zhaozhuo, LIN Mingshan, QIAO Youjin, WU Jiantao. Anti-apoptosis effect and mechanism of heme oxygenase-1 on lung injury after cardiopulmonary bypass. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2017, 24(5): 384-389. doi: 10.7507/1007-4848.201610033 Copy

1.	Wei J, Fan G, Zhao H, et al. Heme oxygenase-1 attenuates inflammation and oxidative damage in a rat model of smoke-induced emphysema. Int J Mol Med, 2015, 36(5): 1384-1392.
2.	Namba F, Go H, Murphy JA, et al. Expression level and subcellular localization of heme oxygenase-1 modulates its cytoprotective properties in response to lung injury: a mouse model. PLoS One, 2014, 9(3): e90936.
3.	Dennery PA. Heme oxygenase in neonatal lung injury and repair. Antioxid Redox Signal, 2014, 21(13): 1881-1892.
4.	黄海嵘, 张雷, 李德闽, 等. 大鼠体外循环后肺损伤的实验研究. 东南国防医药, 2014, 16(2): 113-116.
5.	Fu DR, Kato D, Watabe A, et al. Prognostic utility of apoptosis index, Ki-67 and survivin expression in dogs with nasal carcinoma treated with orthovoltage radiation therapy. J Vet Med Sci, 2014, 76(11): 1505-1512.
6.	Takahashi T, Shimizu H, Morimatsu H, et al. Heme Oxygenase-1 is an essential cytoprotective component in oxidative tissue injury induced by hemorrhagic shock. J Clin Biochem Nutr, 2009, 44(1): 28-40.
7.	Liu PL, Liu JT, Kuo HF, et al. Epigallocatechin gallate attenuates proliferation and oxidative stress in human vascular smooth muscle cells induced by interleukin-1β via heme oxygenase-1. Mediators Inflamm, 2014, 2014: 523684.
8.	Ryter SW, Kim HP, Nakahira K, et al. Protective functions of heme oxygenase-1/carbon monoxide in the respiratory system. Antioxid Redox Signal, 2007, 9(12): 2157-2173.
9.	Yamazaki S, Inamori S, Nakatani T, et al. Activated protein C attenuates cardiopulmonary bypass-induced acute lung injury through the regulation of neutrophil activation. J Thorac Cardiovasc Surg, 2011, 141(5): 1246-1252.
10.	Apostolakis EE, Koletsis EN, Baikoussis NG, et al. Strategies to prevent intraoperative lung injury during cardiopulmonary bypass. J Cardiothorac Surg, 2010, 5: 1.
11.	White LE, Cui Y, Shelak CM, et al. Lung endothelial cell apoptosis during ischemic acute kidney injury. Shock, 2012, 38(3): 320-327.
12.	Deng C, Zhai Z, Wu D, et al. Inflammatory response and pneumocyte apoptosis during lung ischemia-reperfusion injury in an experimental pulmonary thromboembolism model. J Thromb Thrombolysis, 2015, 40(1): 42-53.
13.	Zhang C, Guo Z, Liu H, et al. Influence of levosimendan postconditioning on apoptosis of rat lung cells in a model of ischemia-reperfusion injury. PLoS One, 2015, 10(1): e0114963.
14.	郭海娇, 康凯, 刘焕欣, 等. 紫绀及非紫绀型先心病患者来源的人骨髓间充质干细胞抗凋亡能力的比较. 中国胸心血管外科临床杂志, 2016, 23(12): 1172-1176.
15.	Li Ch, Wu X, Sun R, et al. Croton tiglium extract induces apoptosis via bax/bcl-2 pathways in human lung cancer A549 cells. Asian Pac J Cancer Prev, 2016, 17(11): 4893-4898.
16.	Park EJ, Chauhan AK, Min KJ, et al. Thymoquinone induces apoptosis through downregulation of c-FLIP and Bcl-2 in renal carcinoma Caki cells. Oncol Rep, 2016, 36(4): 2261-2267.
17.	Liang S, Sun K, Wang Y, et al. Role of Cyt-C/caspases-9,3, Bax/Bcl-2 and the FAS death receptor pathway in apoptosis induced by zinc oxide nanoparticles in human aortic endothelial cells and the protective effect by alpha-lipoic acid. Chem Biol Interact, 2016, 258: 40-51.
18.	Zhang Q, Ma S, Liu B, et al. Chrysin induces cell apoptosis via activation of the p53/Bcl-2/caspase-9 pathway in hepatocellular carcinoma cells. Exp Ther Med, 2016, 12(1): 469-474.
19.	Vervliet T, Parys JB, Bultynck G. Bcl-2 proteins and calcium signaling: complexity beneath the surface. Oncogene, 2016, 35(39): 5079-5092.
20.	Jia G, Wang Q, Wang R, et al. Tubeimoside-1 induces glioma apoptosis through regulation of Bax/Bcl-2 and the ROS/Cytochrome C/Caspase-3 pathway. Onco Targets Ther, 2015, 8: 303-311.
21.	Clerc P, Ge SX, Hwang H, et al. Drp1 is dispensable for apoptotic cytochrome c release in primed MCF10A and fibroblast cells but affects Bcl-2 antagonist-induced respiratory changes. Br J Pharmacol, 2014, 171(8): 1988-1999.

1. Wei J, Fan G, Zhao H, et al. Heme oxygenase-1 attenuates inflammation and oxidative damage in a rat model of smoke-induced emphysema. Int J Mol Med, 2015, 36(5): 1384-1392.
2. Namba F, Go H, Murphy JA, et al. Expression level and subcellular localization of heme oxygenase-1 modulates its cytoprotective properties in response to lung injury: a mouse model. PLoS One, 2014, 9(3): e90936.
3. Dennery PA. Heme oxygenase in neonatal lung injury and repair. Antioxid Redox Signal, 2014, 21(13): 1881-1892.
4. 黄海嵘, 张雷, 李德闽, 等. 大鼠体外循环后肺损伤的实验研究. 东南国防医药, 2014, 16(2): 113-116.
5. Fu DR, Kato D, Watabe A, et al. Prognostic utility of apoptosis index, Ki-67 and survivin expression in dogs with nasal carcinoma treated with orthovoltage radiation therapy. J Vet Med Sci, 2014, 76(11): 1505-1512.
6. Takahashi T, Shimizu H, Morimatsu H, et al. Heme Oxygenase-1 is an essential cytoprotective component in oxidative tissue injury induced by hemorrhagic shock. J Clin Biochem Nutr, 2009, 44(1): 28-40.
7. Liu PL, Liu JT, Kuo HF, et al. Epigallocatechin gallate attenuates proliferation and oxidative stress in human vascular smooth muscle cells induced by interleukin-1β via heme oxygenase-1. Mediators Inflamm, 2014, 2014: 523684.
8. Ryter SW, Kim HP, Nakahira K, et al. Protective functions of heme oxygenase-1/carbon monoxide in the respiratory system. Antioxid Redox Signal, 2007, 9(12): 2157-2173.
9. Yamazaki S, Inamori S, Nakatani T, et al. Activated protein C attenuates cardiopulmonary bypass-induced acute lung injury through the regulation of neutrophil activation. J Thorac Cardiovasc Surg, 2011, 141(5): 1246-1252.
10. Apostolakis EE, Koletsis EN, Baikoussis NG, et al. Strategies to prevent intraoperative lung injury during cardiopulmonary bypass. J Cardiothorac Surg, 2010, 5: 1.
11. White LE, Cui Y, Shelak CM, et al. Lung endothelial cell apoptosis during ischemic acute kidney injury. Shock, 2012, 38(3): 320-327.
12. Deng C, Zhai Z, Wu D, et al. Inflammatory response and pneumocyte apoptosis during lung ischemia-reperfusion injury in an experimental pulmonary thromboembolism model. J Thromb Thrombolysis, 2015, 40(1): 42-53.
13. Zhang C, Guo Z, Liu H, et al. Influence of levosimendan postconditioning on apoptosis of rat lung cells in a model of ischemia-reperfusion injury. PLoS One, 2015, 10(1): e0114963.
14. 郭海娇, 康凯, 刘焕欣, 等. 紫绀及非紫绀型先心病患者来源的人骨髓间充质干细胞抗凋亡能力的比较. 中国胸心血管外科临床杂志, 2016, 23(12): 1172-1176.
15. Li Ch, Wu X, Sun R, et al. Croton tiglium extract induces apoptosis via bax/bcl-2 pathways in human lung cancer A549 cells. Asian Pac J Cancer Prev, 2016, 17(11): 4893-4898.
16. Park EJ, Chauhan AK, Min KJ, et al. Thymoquinone induces apoptosis through downregulation of c-FLIP and Bcl-2 in renal carcinoma Caki cells. Oncol Rep, 2016, 36(4): 2261-2267.
17. Liang S, Sun K, Wang Y, et al. Role of Cyt-C/caspases-9,3, Bax/Bcl-2 and the FAS death receptor pathway in apoptosis induced by zinc oxide nanoparticles in human aortic endothelial cells and the protective effect by alpha-lipoic acid. Chem Biol Interact, 2016, 258: 40-51.
18. Zhang Q, Ma S, Liu B, et al. Chrysin induces cell apoptosis via activation of the p53/Bcl-2/caspase-9 pathway in hepatocellular carcinoma cells. Exp Ther Med, 2016, 12(1): 469-474.
19. Vervliet T, Parys JB, Bultynck G. Bcl-2 proteins and calcium signaling: complexity beneath the surface. Oncogene, 2016, 35(39): 5079-5092.
20. Jia G, Wang Q, Wang R, et al. Tubeimoside-1 induces glioma apoptosis through regulation of Bax/Bcl-2 and the ROS/Cytochrome C/Caspase-3 pathway. Onco Targets Ther, 2015, 8: 303-311.
21. Clerc P, Ge SX, Hwang H, et al. Drp1 is dispensable for apoptotic cytochrome c release in primed MCF10A and fibroblast cells but affects Bcl-2 antagonist-induced respiratory changes. Br J Pharmacol, 2014, 171(8): 1988-1999.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Anti-apoptosis effect and mechanism of heme oxygenase-1 on lung injury after cardiopulmonary bypass

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