Mechanism of sufentanil attenuating hepatic ischemia-reperfusion injury in rats

doi:10.11958/20220293

Abstract

Abstract:

Objective To investigate the mechanism of sufentanil preconditioning in reducing hepatic ischemia-reperfusion injury (HIRI) in rats. Methods A total of 48 SD male rats were randomly divided into the Sham operation group (S group), the HIRI group (IR group), the sufentanil pretreatment+HIRI group (SF group), the TGF-β₁ inhibitor+sufentanil pretreatment+HIRI group (SB group), the TGF-β₁ agonist+sufentanil pretreatment+HIRI group (SRI group) and the dimethyl sulfoxide (DMSO)+HIRI group (DMSO group), with 8 rats in each group. The samples were taken 4 hours after the completion of modeling. Then, HE staining was performed to observe the morphological changes of liver tissue. The abdominal aortic blood samples were collected, and the supernatant was collected after centrifugation to measure levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in each group. 10% liver tissue homogenate was prepared to measure levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in each group. The apoptosis rate of hepatocytes was detected by TUNEL method. Western blot method was used to detect the protein expression levels of TGF-β₁, Smad2/3, p-Smad2/3, p38 and p-p38 in liver tissue. Results Compared with the S group, the damage degree was aggravated in the other groups, and levels of ALT, AST, MDA and the hepatocyte apoptosis rate were increased (P<0.05), while the SOD level was decreased (P<0.05). The protein expression levels of TGF-β₁, p-Smad2/3 and p-p38 were increased in the IR group, the SF group and the SRI group (P<0.05), and the protein expression levels of TGF-β₁ and p-p38 were increased in the SB group (P<0.05). Compared with the IR group, the damage degree was reduced in the SF group and the SRI group, and levels of ALT, AST, MDA, the apoptosis rate of hepatocytes and expression level of p-p38 protein were decreased (P<0.05). Levels of SOD, TGF-β₁and p-Smad2/3 protein were increased (P<0.05), the damage degree was increased in the SB group, and levels of ALT, AST, MDA, apoptosis rate of hepatocytes and the expression level of p-p38 protein were increased (P<0.05). Levels of SOD, TGF-β₁and p-Smad2/3 protein were decreased (P<0.05). Compared with SF group, the damage degree of SB group was aggravated, levels of ALT, AST and MDA, the apoptosis rate of hepatocytes, the expression level of p-p38 protein were all increased (P<0.05), and SOD, TGF-β₁, p-Smad2/3 protein expression levels were decreased (P<0.05). The damage degree of SRI group was reduced, levels of ALT, AST, the apoptosis rate of hepatocytes and the expression level of p-p38 protein were decreased (P<0.05), while levels of SOD, TGF-β₁ and p-Smad2/3 protein were increased (P<0.05). Conclusion Sufentanil pretreatment may inhibit the phosphorylation of p38 MAPK by activating the TGF-β/Smad signaling pathway, reducing hepatocyte apoptosis and oxidative stress, thus playing a protective role on HIRI in rats.

Key words: sufentanil, reperfusion injury, liver, apoptosis, oxidative stress, p38 mitogen-activated protein linases, transforming growth factor β/Smad signaling pathway

CLC Number:

R614

Figures/Tables 5

References 14

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组别	ALT（U/L）	AST（U/L）	MDA（μmol/g）	SOD（U/mg）
S组	45.33±6.96	80.66±11.56	0.28±0.03	263.70±14.69
IR组	808.70±24.38^a	1 125.00±106.70^a	0.85±0.04^a	143.80±6.61^a
SF组	453.70±23.96^ab	653.40±30.85^ab	0.67±0.04^ab	183.20±8.20^ab
SB组	971.00±29.06^abc	1 593.00±204.30^abc	1.26±0.12^abc	98.08±4.44^abc
SRI组	226.40±18.25^abc	368.80±22.93^abc	0.38±0.05^ab	223.50±12.28^abc
DMSO组	807.70±16.60^ac	1 135.00±16.50^ac	0.88±0.05^ac	141.40±9.09^ac
F	2 442.000^＊＊	184.700^＊＊	263.400^＊＊	302.800^＊＊

组别	ALT（U/L）	AST（U/L）	MDA（μmol/g）	SOD（U/mg）
S组	45.33±6.96	80.66±11.56	0.28±0.03	263.70±14.69
IR组	808.70±24.38^a	1 125.00±106.70^a	0.85±0.04^a	143.80±6.61^a
SF组	453.70±23.96^ab	653.40±30.85^ab	0.67±0.04^ab	183.20±8.20^ab
SB组	971.00±29.06^abc	1 593.00±204.30^abc	1.26±0.12^abc	98.08±4.44^abc
SRI组	226.40±18.25^abc	368.80±22.93^abc	0.38±0.05^ab	223.50±12.28^abc
DMSO组	807.70±16.60^ac	1 135.00±16.50^ac	0.88±0.05^ac	141.40±9.09^ac
F	2 442.000^＊＊	184.700^＊＊	263.400^＊＊	302.800^＊＊

组别	TGF-β₁	Smad2/3	p-Smad2/3	p38	p-p38
S组	0.548±0.004	1.028±0.056	0.674±0.014	1.053±0.005	0.287±0.002
IR组	1.497±0.015^a	0.985±0.007	0.851±0.039^a	1.034±0.020	3.627±0.132^a
SF组	1.929±0.020^ab	0.998±0.005	1.152±0.015^ab	1.038±0.018	1.941±0.066^ab
SB组	0.930±0.022^abc	0.984±0.017	0.707±0.008^bc	1.034±0.006	4.127±0.293^abc
SRI组	2.064±0.050^abc	0.983±0.023	1.592±0.048^abc	1.034±0.008	1.041±0.062^abc
F	1 710.000^＊＊	1.383	511.800^＊＊	1.250	365.100^＊＊

组别	TGF-β₁	Smad2/3	p-Smad2/3	p38	p-p38
S组	0.548±0.004	1.028±0.056	0.674±0.014	1.053±0.005	0.287±0.002
IR组	1.497±0.015^a	0.985±0.007	0.851±0.039^a	1.034±0.020	3.627±0.132^a
SF组	1.929±0.020^ab	0.998±0.005	1.152±0.015^ab	1.038±0.018	1.941±0.066^ab
SB组	0.930±0.022^abc	0.984±0.017	0.707±0.008^bc	1.034±0.006	4.127±0.293^abc
SRI组	2.064±0.050^abc	0.983±0.023	1.592±0.048^abc	1.034±0.008	1.041±0.062^abc
F	1 710.000^＊＊	1.383	511.800^＊＊	1.250	365.100^＊＊

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