Penehyclidine hydrochloride exerts protective effects in rats with acute lung injury via the Fas/FasL signaling pathway

Kong,Qian; Wu,Xiaojing; Duan,Weina; Zhan,Liying; Song,Xuemin

doi:10.3892/etm.2019.7340

Penehyclidine hydrochloride exerts protective effects in rats with acute lung injury via the Fas/FasL signaling pathway

Authors:
- Qian Kong
- Xiaojing Wu
- Weina Duan
- Liying Zhan
- Xuemin Song
View Affiliations

Affiliations: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: March 4, 2019 https://doi.org/10.3892/etm.2019.7340
Pages: 3598-3606
Copyright: © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Acute lung injury (ALI) is a critical syndrome that is associated with high morbidity and mortality rates. The activation of the Fas/Fas ligand (FasL) signaling pathway may be an important pathophysiological mechanism during ALI development. Penehyclidine hydrochloride (PHC) has been revealed to exhibit anti‑apoptotic properties and may attenuate the observed systemic inflammatory response. The present study was performed to elucidate the molecular mechanism of PHC in the regulation of the Fas/FasL signaling pathway in rats with ALI. An ALI rat model was constructed by inducing blunt chest trauma and hemorrhagic shock (T/HS), with PHC administration prior to or following T/HS. At 6 h following T/HS, blood samples and lung tissues were collected. Western blotting, arterial blood gas analysis, ELISA, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling staining and biochemical indicator analysis were performed to determine the degree of lung injury and the key signaling pathways associated with lung damage. The results indicated that the administration of PHC following T/HS effectively attenuates lung injury by improving pulmonary oxygenation, decreasing histopathological damage, decreasing polymorphonuclear neutrophil count and decreasing Fas, FasL, caspase‑8, caspase‑3, tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑1β expression. The results indicated that PHC exhibits anti‑apoptotic functions and exerts protective effects in ALI rats induced by T/HS, which may be attributed to the inhibition of the Fas/FasL signaling pathway.

View Figures

View References

1	Liu Y, Du DY, Hu X, Xia DK, Xiang XY, Huang C, Zhou JH and Jiang JX: Prevalence and mortality of severe chest trauma in three gorges area of China. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 34:567–572. 2012.(In Chinese). PubMed/NCBI
2	Erickson SE, Martin GS, Davis JL, Matthay MA and Eisner MD; NIH NHLBI ARDS Network, : Recent trends in acute lung injury mortality: 1996–2005. Crit Care Med. 37:1574–1579. 2009. View Article : Google Scholar : PubMed/NCBI
3	Gallagher JJ: Management of blunt pulmonary injury. AACN Adv Crit Care. 25:375–386. 2014. View Article : Google Scholar : PubMed/NCBI
4	Brown LM, Kallet RH, Matthay MA and Dicker RA: The influence of race on the development of acute lung injury in trauma patients. Am J Surg. 201:486–491. 2011. View Article : Google Scholar : PubMed/NCBI
5	Messer MP, Kellermann P, Weber SJ, Hohmann C, Denk S, Klohs B, Schultze A, Braumüller S, Huber-Lang MS and Perl M: Silencing of fas, fas-associated via death domain, or caspase 3 differentially affects lung inflammation, apoptosis, and development of trauma-induced septic acute lung injury. Shock. 39:19–27. 2013.PubMed/NCBI
6	Thakkar RK, Chung CS, Chen Y, Monaghan SF, Lomas-Neira J, Heffernan DS, Cioffi WG and Ayala A: Local tissue expression of the cell death ligand, fas ligand, plays a central role in the development of extrapulmonary acute lung injury. Shock. 36:138–143. 2011. View Article : Google Scholar : PubMed/NCBI
7	Glavan BJ, Holden TD, Goss CH, Black RA, Neff MJ, Nathens AB, Martin TR and Wurfel MM; ARDSnet Investigators, : Genetic variation in the FAS gene and associations with acute lung injury. Am J Respir Crit Care Med. 183:356–363. 2011. View Article : Google Scholar : PubMed/NCBI
8	Herrero R, Tanino M, Smith LS, Kajikawa O, Wong VA, Mongovin S, Matute-Bello G and Martin TR: The Fas/FasL pathway impairs the alveolar fluid clearance in mouse lungs. Am J Physiol Lung Cell Mol Physiol. 305:L377–L388. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wang Z, Lin D, Zhang L, Liu W, Tan H and Ma J: Penehyclidine hydrochloride prevents anoxia/reoxygenation injury and induces H9c2 cardiomyocyte apoptosis via a mitochondrial pathway. Eur J Pharmacol. 797:115–123. 2017. View Article : Google Scholar : PubMed/NCBI
10	Yang Y, Zhao L and Ma J: Penehyclidine hydrochloride preconditioning provides cardiac protection in a rat model of myocardial ischemia/reperfusion injury via the mechanism of mitochondrial dynamics mechanism. Eur J Pharmacol. 813:130–139. 2017. View Article : Google Scholar : PubMed/NCBI
11	Zhu R, Zhao Y, Li X, Bai T, Wang S, Wang W and Sun Y: Effects of penehyclidine hydrochloride on severe acute pancreatitis-associated acute lung injury in rats. Biomed Pharmacother. 97:1689–1693. 2018. View Article : Google Scholar : PubMed/NCBI
12	Wu XJ, Liu HM, Song XM, Zhao B, Leng Y, Wang EY, Zhan LY, Meng QT and Xia ZY: Penehyclidine hydrochloride inhibits TLR4 signaling and inflammation, and attenuates blunt chest trauma and hemorrhagic shock-induced acute lung injury in rats. Mol Med Rep. 17:6327–6336. 2018.PubMed/NCBI
13	Zheng F, Xiao F, Yuan QH, Liu QS, Zhang ZZ, Wang YL and Zhan J: Penehyclidine hydrochloride decreases pulmonary microvascular endothelial inflammatory injury through a beta-arrestin-1-dependent mechanism. Inflammation. 41:1610–1620. 2018. View Article : Google Scholar : PubMed/NCBI
14	Wang LL, Zhan LY, Wu XJ and Xia ZY: Effects of penehyclidine hydrochloride on apoptosis of lung tissues in rats with traumatic acute lung injury. Chin J Traumatol. 13:15–19. 2010.PubMed/NCBI
15	Cui J, Li CS, He XH and Song YG: Protective effects of penehyclidine hydrochloride on acute lung injury caused by severe dichlorvos poisoning in swine. Chin Med J (Engl). 126:4764–4770. 2013.PubMed/NCBI
16	Wu XJ, Xia ZY, Wang LL, Luo T, Zhan LY, Meng QT and Song XM: Effects of penehyclidine hydrochloride on pulmonary contusion from blunt chest trauma in rats. Injury. 43:232–236. 2012. View Article : Google Scholar : PubMed/NCBI
17	Raghavendran K, Davidson BA, Helinski JD, Marschke CJ, Manderscheid P, Woytash JA, Notter RH and Knight PR: A rat model for isolated bilateral lung contusion from blunt chest trauma. Anesth Analg. 101:1482–1489. 2005. View Article : Google Scholar : PubMed/NCBI
18	Wu X, Song X, Li N, Zhan L, Meng Q and Xia Z: Protective effects of dexmedetomidine on blunt chest trauma-induced pulmonary contusion in rats. J Trauma Acute Care Surg. 74:524–530. 2013. View Article : Google Scholar : PubMed/NCBI
19	Kellner M, Noonepalle S, Lu Q, Srivastava A, Zemskov E and Black SM: ROS signaling in the pathogenesis of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). Adv Exp Med Biol. 967:105–137. 2017. View Article : Google Scholar : PubMed/NCBI
20	Wu DQ, Wu HB, Zhang M and Wang JA: Effects of zinc finger protein A20 on Lipopolysaccharide (LPS)-induced pulmonary inflammation/anti-inflammatory mediators in an acute lung injury/acute respiratory distress syndrome rat model. Med Sci Monit. 23:3536–3545. 2017. View Article : Google Scholar : PubMed/NCBI
21	Agarwal R, Handa A, Aggarwal AN, Gupta D and Behera D: Outcomes of noninvasive ventilation in acute hypoxemic respiratory failure in a respiratory intensive care unit in north India. Respir Care. 54:1679–1887. 2009.PubMed/NCBI
22	Han F, Luo Y, Li Y, Liu Z, Xu D, Jin F and Li Z: Seawater induces apoptosis in alveolar epithelial cells via the Fas/FasL-mediated pathway. Respir Physiol Neurobiol. 182:71–80. 2012. View Article : Google Scholar : PubMed/NCBI
23	Seitz DH, Palmer A, Niesler U, Braumüller ST, Bauknecht S, Gebhard F and Knöferl MW: Altered expression of Fas receptor on alveolar macrophages and inflammatory effects of soluble Fas ligand following blunt chest trauma. Shock. 35:610–617. 2011. View Article : Google Scholar : PubMed/NCBI
24	Kobata T, Takasaki K, Asahara H, Hong NM, Masuko-Hongo K, Kato T, Hirose S, Shirai T, Kayagaki N, Yagita H, et al: Apoptosis with FasL+ cell infiltration in the periphery and thymus of corrected autoimmune mice. Immunology. 92:206–213. 1997. View Article : Google Scholar : PubMed/NCBI
25	Gil S, Farnand AW, Altemeier WA, Gill SE, Kurdowska A, Krupa A, Florence JM and Matute-Bello G: Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody: KC complexes in a model of acute lung injury. Respir Res. 13:912012. View Article : Google Scholar : PubMed/NCBI
26	Weckbach S, Hohmann C, Braumueller S, Denk S, Klohs B, Stahel PF, Gebhard F, Huber-Lang MS and Perl M: Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: Distinct early response compared with single trauma or ‘double-hit’ injury. J Trauma Acute Care Surg. 74:489–498. 2013. View Article : Google Scholar : PubMed/NCBI
27	Serrao KL, Fortenberry JD, Owens ML, Harris FL and Brown LA: Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand. Am J Physiol Lung Cell Mol Physiol. 280:L298–L305. 2001. View Article : Google Scholar : PubMed/NCBI
28	Perl M, Hohmann C, Denk S, Kellermann P, Lu D, Braumüller S, Bachem MG, Thomas J, Knöferl MW, Ayala A, et al: Role of activated neutrophils in chest trauma-induced septic acute lung injury. Shock. 38:98–106. 2012. View Article : Google Scholar : PubMed/NCBI
29	Li H, Qian Z, Li J, Han X and Liu M: Effects of early administration of a novel anticholinergic drug on acute respiratory distress syndrome induced by sepsis. Med Sci Monit. 11:BR319–BR325. 2011.
30	Shen W, Gan J, Xu S, Jiang G and Wu H: Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway. Pharmacol Res. 60:296–302. 2009. View Article : Google Scholar : PubMed/NCBI
31	Han XY, Liu H, Liu CH, Wu B, Chen LF, Zhong BH and Liu KL: Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018). Bioorg Med Chem Lett. 15:1979–1982. 2005. View Article : Google Scholar : PubMed/NCBI
32	Tan H, Chen L and Ma J: Penehyclidine hydrochloride post-conditioning reduces ischemia/reperfusion-induced cardiomyocyte apoptosis in rats. Exp Ther Med. 14:4272–4278. 2017.PubMed/NCBI
33	Wang D, Jiang Q and Du X: Protective effects of scopolamine and penehyclidine hydrochloride on acute cerebral ischemia-reperfusion injury after cardiopulmonary resuscitation and effects on cytokines. Exp Ther Med. 15:2027–2031. 2018.PubMed/NCBI
34	Wu GM, Mou M, Mo LQ, Liu L, Ren CH, Chen Y and Zhou J: Penehyclidine hydrochloride postconditioning on lipopolysaccharide-induced acute lung injury by inhibition of inflammatory factors in a rodent model. J Surg Res. 195:219–227. 2015. View Article : Google Scholar : PubMed/NCBI
35	Cao HJ, Sun YJ, Zhang TZ, Zhou J and Diao YG: Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass. Can J Physiol Pharmacol. 91:521–527. 2013. View Article : Google Scholar : PubMed/NCBI
36	Wang YP, Li G, Ma LL, Zheng Y, Zhang SD, Zhang HX, Qiu M and Ma X: Penehyclidine hydrochloride ameliorates renal ischemia-reperfusion injury in rats. J Surg Res. 186:390–397. 2014. View Article : Google Scholar : PubMed/NCBI