Fibrinogen-like protein 2 aggravates myocardial ischemia/reperfusion injury in mice following sevoflurane anesthetic through ROS production by PPAR

This study aims to investigate the mechanism and effects of Fibrinogen-like protein 2 (FGL2) in myocardial ischemia/reperfusion injury in mice following sevoflurane anesthetic. Mice of SAP group were placed in box with oxygen and anesthetic gas (60 mg/kg, pentobarbital), 2.5% Sevoflurane was pumped into the box for 1 h. H9C2 cells were treated by 3% sevoflurane for 6 h and a mixture of 95% O2 + 5% CO2 for 24 h. Fgl2 mRNA expression was up-regulated in mice of I/R injury following sevoflurane. Fgl2 protein reduced HR, LVDP, dp/dtmax (+) and dp/dtmax (-), increased LVEDP levels, myocardial infarct size and AI in mice of I/R injury following sevoflurane. Fgl2 suppressed PPAR signaling pathway, and promoted ROS production in vivo or vitro model. The activation of PPAR signaling pathway reduced the function of Fgl2 in vivo and vitro model. Fgl2 might serve as a therapeutic target in the treatment of I/R injury following sevoflurane. We hope that our findings will pave a way for future therapies against I/R injury following sevoflurane.

Keywords:
FGL2; myocardial ischemia/reperfusion injury; sevoflurane; ROS production; PPAR

Authorship

Wen BIAN

Department of Anesthesiology, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, Jinan City, Shandong Province, PR ChinaShandong Provincial ENT HospitalPR ChinaJinan City, Shandong Province, PR ChinaDepartment of Anesthesiology, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, Jinan City, Shandong Province, PR China

Fengmei JIAO

Guiting LI

Wei CHEN ^**Corresponding author: cwchenwei12@163.com

Operating Room, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, Jinan City, Shandong Province, PR ChinaShandong Provincial ENT HospitalPR ChinaJinan City, Shandong Province, PR ChinaOperating Room, Shandong Second Provincial General Hospital, Shandong Provincial ENT Hospital, Jinan City, Shandong Province, PR China

http://orcid.org/0000-0001-8188-8096

*Corresponding author: cwchenwei12@163.com

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (6)

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Figure 1
Fgl2 aggravates myocardial I/R injury following sevoflurane. Fgl2 mRNA expression in mice of I/R injury following sevoflurane (A); LVDP (B), LVEDP (C), dp/dtmax (+) (D), dp/dtmax (-) (E), myocardial infarct size (F), myocardial tissues of mice by HE staining (G), AI (H) and HR (I) in mice of I/R injury following sevoflurane by Fgl2 protein. Sham, sham control mice group; I/R, I/R injury mice group; I/R+SAP, I/R injury mice with sevoflurane group; Fgl2+I/R+SAP, I/R injury mice with sevoflurane and Fgl2 protein group. ##p<0.01 compared with sham control mice group or I/R injury mice with sevoflurane group; ###p<0.01 compared with I/R injury mice group.

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Figure 2
Fgl2 suppressed PPAR signaling pathway in vivo model. Heat map, results figure and refine results of gene chip (A, B and C); Fgl2 and PPARγ protein expression in vitro model by over-expression of Fgl2 (D, E and F); Fgl2 and PPARγ protein expression in vitro model by down-regulation of Fgl2 (G, H and I); PPARγ protein expression in mice of I/R injury following sevoflurane by Fgl2 protein (J and K); PPARγ protein expression in vitro model by over-expression of Fgl2 (IF, L). Negative, negative mimics group; Fgl2, over-expression of Fgl2 group; SiFgl2, down-regulation of Fgl2 group; I/R injury mice with sevoflurane group; Fgl2+I/R+SAP, I/R injury mice with sevoflurane and Fgl2 protein group. ##p<0.01 compared with negative mimics group or I/R injury mice with sevoflurane group.

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Figure 3
Fgl2 promoted ROS production in vitro model. ROS production (A and B), MDA (C), SOD (D), GSH (E) and GSH-px (F) levels in vitro model by over-expression of Fgl2; ROS production (G and H), MDA (I), SOD (J), GSH (K) and GSH-px (L) levels in vitro model by down-regulation of Fgl2. Negative, negative mimics group; Fgl2, over-expression of Fgl2 group; SiFgl2, down-regulation of Fgl2 group. ##p<0.01 compared with negative mimics group.

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Figure 4
The activation of PPAR signaling pathway reduced the function of Fgl2 in vivo and vitro model. PPARγ protein expression (A and B), HR (C), LVDP (D), LVEDP (E), dp/dtmax (+) (F), dp/dtmax (-) (G), myocardial infarct size (H), myocardial tissues of mice by HE staining (G), AI (I) and HR (J), MDA (K), SOD (L), GSH (M) and GSH-px levels (N) in mice of I/R injury following sevoflurane. Control, I/R injury mice with sevoflurane group; Anti-Fgl2, I/R injury mice with sevoflurane by anti-Fgl2 group; Anti-Fgl2+PPAR i, I/R injury mice with sevoflurane by anti-Fgl2 and GW9662 group. ##p<0.01 compared with I/R injury mice with sevoflurane group; ###p<0.01 compared with I/R injury mice with sevoflurane by anti-Fgl2 group.

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Figure 5
The inactivation of PPAR signaling pathway reduced the function of siFgl2 in vitro model. PPARγ protein expression (A and B), ROS production (C and D), MDA (E), SOD (F), GSH (G) and GSH-px (H) levels. Negative, negative mimics group; SiFgl2, down-regulation of Fgl2 group; SiFgl2+siPPAR, down-regulation of Fgl2 and PPAR group. ##p<0.01 compared with negative mimics group; ###p<0.01 compared with down-regulation of Fgl2 group.

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Figure 6
The activation of PPAR signaling pathway reduced the function of Fgl2 in vivo and vitro model. PPARγ protein expression (A and B), ROS production (C and D), MDA (E), SOD (F), GSH (G) and GSH-px (H) levels. Negative, negative mimics group; Fgl2, over-expression of Fgl2 group; Fgl2+PPAR, over-expression of Fgl2 and PPAR group. ##p<0.01 compared with negative mimics group; ###p<0.01 compared with over-expression of Fgl2 group.

Figure 1 Fgl2 aggravates myocardial I/R injury following sevoflurane. Fgl2 mRNA expression in mice of I/R injury following sevoflurane (A); LVDP (B), LVEDP (C), dp/dtmax (+) (D), dp/dtmax (-) (E), myocardial infarct size (F), myocardial tissues of mice by HE staining (G), AI (H) and HR (I) in mice of I/R injury following sevoflurane by Fgl2 protein. Sham, sham control mice group; I/R, I/R injury mice group; I/R+SAP, I/R injury mice with sevoflurane group; Fgl2+I/R+SAP, I/R injury mice with sevoflurane and Fgl2 protein group. ##p<0.01 compared with sham control mice group or I/R injury mice with sevoflurane group; ###p<0.01 compared with I/R injury mice group.

Figure 2 Fgl2 suppressed PPAR signaling pathway in vivo model. Heat map, results figure and refine results of gene chip (A, B and C); Fgl2 and PPARγ protein expression in vitro model by over-expression of Fgl2 (D, E and F); Fgl2 and PPARγ protein expression in vitro model by down-regulation of Fgl2 (G, H and I); PPARγ protein expression in mice of I/R injury following sevoflurane by Fgl2 protein (J and K); PPARγ protein expression in vitro model by over-expression of Fgl2 (IF, L). Negative, negative mimics group; Fgl2, over-expression of Fgl2 group; SiFgl2, down-regulation of Fgl2 group; I/R injury mice with sevoflurane group; Fgl2+I/R+SAP, I/R injury mice with sevoflurane and Fgl2 protein group. ##p<0.01 compared with negative mimics group or I/R injury mice with sevoflurane group.

Figure 3 Fgl2 promoted ROS production in vitro model. ROS production (A and B), MDA (C), SOD (D), GSH (E) and GSH-px (F) levels in vitro model by over-expression of Fgl2; ROS production (G and H), MDA (I), SOD (J), GSH (K) and GSH-px (L) levels in vitro model by down-regulation of Fgl2. Negative, negative mimics group; Fgl2, over-expression of Fgl2 group; SiFgl2, down-regulation of Fgl2 group. ##p<0.01 compared with negative mimics group.

Figure 4 The activation of PPAR signaling pathway reduced the function of Fgl2 in vivo and vitro model. PPARγ protein expression (A and B), HR (C), LVDP (D), LVEDP (E), dp/dtmax (+) (F), dp/dtmax (-) (G), myocardial infarct size (H), myocardial tissues of mice by HE staining (G), AI (I) and HR (J), MDA (K), SOD (L), GSH (M) and GSH-px levels (N) in mice of I/R injury following sevoflurane. Control, I/R injury mice with sevoflurane group; Anti-Fgl2, I/R injury mice with sevoflurane by anti-Fgl2 group; Anti-Fgl2+PPAR i, I/R injury mice with sevoflurane by anti-Fgl2 and GW9662 group. ##p<0.01 compared with I/R injury mice with sevoflurane group; ###p<0.01 compared with I/R injury mice with sevoflurane by anti-Fgl2 group.

Figure 5 The inactivation of PPAR signaling pathway reduced the function of siFgl2 in vitro model. PPARγ protein expression (A and B), ROS production (C and D), MDA (E), SOD (F), GSH (G) and GSH-px (H) levels. Negative, negative mimics group; SiFgl2, down-regulation of Fgl2 group; SiFgl2+siPPAR, down-regulation of Fgl2 and PPAR group. ##p<0.01 compared with negative mimics group; ###p<0.01 compared with down-regulation of Fgl2 group.

Figure 6 The activation of PPAR signaling pathway reduced the function of Fgl2 in vivo and vitro model. PPARγ protein expression (A and B), ROS production (C and D), MDA (E), SOD (F), GSH (G) and GSH-px (H) levels. Negative, negative mimics group; Fgl2, over-expression of Fgl2 group; Fgl2+PPAR, over-expression of Fgl2 and PPAR group. ##p<0.01 compared with negative mimics group; ###p<0.01 compared with over-expression of Fgl2 group.

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Fibrinogen-like protein 2 aggravates myocardial ischemia/reperfusion injury in mice following sevoflurane anesthetic through ROS production by PPAR

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[1] *Corresponding author: cwchenwei12@163.com