Effects of SB202190 on expression levels of IL-6 and NF-κB in flap ischemia-reperfusion injury

Guo,Kai; Ma,Jingxin; Liang,Wenyong

doi:10.3892/etm.2018.6442

Effects of SB202190 on expression levels of IL-6 and NF-κB in flap ischemia-reperfusion injury

Authors:
- Kai Guo
- Jingxin Ma
- Wenyong Liang
View Affiliations

Affiliations: Department III of Orthopaedics, Jinan Municipal Hospital of Traditional Chinese Medicine, Jinan, Shandong 250000, P.R. China, Department of Spine Surgery, Jinan Zhangqiu District Hospital of Traditional Chinese Medicine,Jinan, Shandong 250000, P.R. China, Department of Hand, Foot and Ankle Surgery, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China
Published online on: July 13, 2018 https://doi.org/10.3892/etm.2018.6442
Pages: 2522-2526
Copyright: © Guo 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

The aim of the current study was to investigate the effect of SB202190, a specific inhibitor of p38 MAPK signaling pathway, on the expression levels of IL-6 and NF-κB in flap ischemia-reperfusion injury. Healthy Sprague-Dawley rats were randomly divided into four groups of 12 each. For the ischemia-reperfusion group, the flap was constructed and then sutured after 8 h of ischemia. For the saline group, rats were intraperitoneally infused with saline at regular intervals after flap ischemia-reperfusion. For the inhibitor group, rats were intraperitoneally infused with SB202190 at regular intervals after flap ischemia-reperfusion. For the control group, the flap was constructed and then sutured immediately. The flap survival rate of each group was measured after 7 days. The concentration of IL-6 in serum was measured by ELISA kit. The mRNA and protein expression levels of IL-6 and NF-κB in the flap were measured using RT-PCR and western blot analysis, respectively. In the ischemia-reperfusion group and the saline group, the flap survival rates were much lower than that in the control group (P<0.05). By contrast, the mRNA and protein expression levels of IL-6 and NF-κB in the flap and the concentration of IL-6 in serum were much higher (P<0.05). In the inhibitor group, the flap survival rate was significantly higher than those in the ischemia-reperfusion and saline groups (P<0.05). By contrast, the concentration of IL-6 in serum and the mRNA and protein expression levels of NF-κB and IL-6 in the flap were significantly decreased (P<0.05). The results show that, SB202190 played a role in the protection of the flap by reducing the inflammatory response in flap ischemia-reperfusion injury.

View Figures

View References

1	Cheng HF, Feng Y, Jiang DM, Tao KY and Kong MJ: Protective function of tocilizumab in human cardiac myocytes ischemia reperfusion injury. Asian Pac J Trop Med. 8:48–52. 2015. View Article : Google Scholar : PubMed/NCBI
2	Khalil AA, Aziz FA and Hall JC: Reperfusion injury. Plast Reconstr Surg. 117:1024–1033. 2006. View Article : Google Scholar : PubMed/NCBI
3	Uchida Y, Freitas MC, Zhao D, Busuttil RW and Kupiec-Weglinski JW: The protective function of neutrophil elastase inhibitor in liver ischemia/reperfusion injury. Transplantation. 89:1050–1056. 2010. View Article : Google Scholar : PubMed/NCBI
4	Kanemoto S, Matsubara M, Noma M, Leshnower BG, Parish LM, Jackson BM, Hinmon R, Hamamoto H, Gorman JH III and Gorman RC: Mild hypothermia to limit myocardial ischemia-reperfusion injury: Importance of timing. Ann Thorac Surg. 87:157–163. 2009. View Article : Google Scholar : PubMed/NCBI
5	Liu YQ, Liu YF, Ma XM, Xiao YD, Wang YB, Zhang MZ, Cheng AX, Wang TT, Li JL, Zhao PX, et al: Hydrogen-rich saline attenuates skin ischemia/reperfusion induced apoptosis via regulating Bax/Bcl-2 ratio and ASK-1/JNK pathway. J Plast Reconstr Aesthet Surg. 68:e147–e156. 2015. View Article : Google Scholar : PubMed/NCBI
6	Ashraf MI, Ebner M, Wallner C, Haller M, Khalid S, Schwelberger H, Koziel K, Enthammer M, Hermann M, Sickinger S, et al: A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury. Cell Commun Signal. 12:62014. View Article : Google Scholar : PubMed/NCBI
7	Uemura T, Tsujii M, Akeda K, Iino T, Satonaka H, Hasegawa M and Sudo A: Transfection of nuclear factor-kappaB decoy oligodeoxynucleotide protects against ischemia/reperfusion injury in a rat epigastric flap model. J Gene Med. 14:623–631. 2012. View Article : Google Scholar : PubMed/NCBI
8	Grossi V, Liuzzi M, Murzilli S, Martelli N, Napoli A, Ingravallo G, Del Rio A and Simone C: Sorafenib inhibits p38α activity in colorectal cancer cells and synergizes with the DFG-in inhibitor SB202190 to increase apoptotic response. Cancer Biol Ther. 13:1471–1481. 2012. View Article : Google Scholar : PubMed/NCBI
9	Manson PN, Anthenelli RM, Im MJ, Bulkley GB and Hoopes JE: The role of oxygen-free radicals in ischemic tissue injury in island skin flaps. Ann Surg. 198:87–90. 1983. View Article : Google Scholar : PubMed/NCBI
10	Al-Juboori MJ: Flap designs for implant-related surgical procedures: A review. Implant Dent. 25:845–854. 2016. View Article : Google Scholar : PubMed/NCBI
11	Silva JJ, Pompeu DG, Ximenes NC, Duarte AS, Gramosa NV, Carvalho KM, Brito GA and Guimarães SB: Effects of kaurenoic acid and arginine on random skin flap oxidative stress, inflammation, and cytokines in rats. Aesthetic Plast Surg. 39:971–977. 2015. View Article : Google Scholar : PubMed/NCBI
12	Joshi YB and Praticò D: The 5-lipoxygenase pathway: Oxidative and inflammatory contributions to the Alzheimer's disease phenotype. Front Cell Neurosci. 8:4362015. View Article : Google Scholar : PubMed/NCBI
13	Patten RD, Pourati I, Aronovitz MJ, Baur J, Celestin F, Chen X, Michael A, Haq S, Nuedling S, Grohe C, et al: 17beta-estradiol reduces cardiomyocyte apoptosis in vivo and in vitro via activation of phospho-inositide-3 kinase/Akt signaling. Circ Res. 95:692–699. 2004. View Article : Google Scholar : PubMed/NCBI
14	Ju J, Wu J and Hou R: Role of the p38 mitogen-activated protein kinase signaling pathway in estrogen-mediated protection following flap ischemia-reperfusion injury. Cell Biochem Funct. 34:522–530. 2016. View Article : Google Scholar : PubMed/NCBI
15	Han HH, Lim YM, Park SW, Lee SJ, Rhie JW and Lee JH: Improved skin flap survival in venous ischemia-reperfusion injury with the use of adipose-derived stem cells. Microsurgery. 35:645–652. 2015. View Article : Google Scholar : PubMed/NCBI
16	Denes A, Thornton P, Rothwell NJ and Allan SM: Inflammation and brain injury: Acute cerebral ischaemia, peripheral and central inflammation. Brain Behav Immun. 24:708–723. 2010. View Article : Google Scholar : PubMed/NCBI
17	Suzuki S, Tanaka K and Suzuki N: Ambivalent aspects of interleukin-6 in cerebral ischemia: Inflammatory versus neurotrophic aspects. J Cereb Blood Flow Metab. 29:464–479. 2009. View Article : Google Scholar : PubMed/NCBI
18	Clark WM, Rinker LG, Lessov NS, Hazel K, Hill JK, Stenzel-Poore M, Eckenstein F and Haley EC: Lack of interleukin-6 expression is not protective against focal central nervous system ischemia. Stroke. 31:1715–1720. 2000. View Article : Google Scholar : PubMed/NCBI
19	Liu SF and Malik AB: NF-kappa B activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol. 290:L622–L645. 2006. View Article : Google Scholar : PubMed/NCBI
20	Wang J, Min P, Grassetti L, Lazzeri D, Zhang YX, Nicoli F, Innocenti M, Torresetti M, Levin LS and Persichetti P: Preliminary outcomes of distal IMAP and SEAP flaps for the treatment of unstable keloids subject to recurrent inflammation and infections in the lower sternal and upper abdominal areas. J Reconstr Microsurg. 31:621–630. 2015. View Article : Google Scholar : PubMed/NCBI