Protective effect of propofol on myocardial injury and related signal pathways in rats with intestinal ischemia-reperfusion injury

doi:10.3877/cma.j.issn.2095-1221.2021.05.007

Abstract

Abstract:

Objective

To explore the protective effect of propofol on myocardial injury in rats with intestinal ischemia-reperfusion injury and mechanism thereof.

Methods

Rat models of intestinal ischemia-reperfusion injury were constructed and divided into model group, sham operation group (sham operation group and model group by intraperitoneal injection of fat emulsion) , low, medium and high dose propofol group (5, 10, and 20 mg/kg propofol were injected intraperitoneally 30 minutes before surgery) . After 2 hours of reperfusion, hematoxylin-eosin (HE) staining was used to observe the pathological changes of the small intestinal tissue and cardiac muscle tissue in the rats; TUNEL assay was used to detect rat cardiomyocyte apoptosis; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum malondialdehyde (MDA) , glutathione peroxidase (GSH-Px) , superoxide dismutase (SOD) and interleukin 1β (IL-1β) , IL-6, and tumor necrosis factor α (TNF-α) in the rats; Western blot was used to detect the expressions of silent information regulation factor 2 related enzyme 1 (Sirt1) and acetylated forkhead transcription factor 1 (Ac- Foxo1) proteins in rat myocardial tissues. One-way analysis of variance was used for the comparison between multiple groups, and SNK-q test was used for further comparison between two groups.

Results

Compared with the sham operation group, the small intestinal tissue of the model group was severely edematous and partially necrotic, the structure of the small intestinal mucosa was damaged, the villi were obviously shedding, myocardial cells were swollen, and a large number of inflammatory cell infiltration appeared in the interstitium. The myocardial cells apoptosis rate [ (4.05±0.37) ﹪vs (34.24±4.28) ﹪], Ac-Foxo1 expression (0.80±0.14 vs 2.21±0.25) , MDA content [ (4.09±0.81) nmol/mg vs (12.64±2.10) nmol/ mg], and the levels of TNF-α [ (19.26±3.48) pg/ mg vs (85.37±10.41) pg/ mg], IL-1β [ (9.53±1.14) pg/ mg vs (57.82±7.36) pg/ mg], and IL-6 [ (8.49±2.03) pg/mg vs (50.76±6.28) pg/mg] were increased significantly (P < 0.05) ; Sirt1 expression (1.15±0.17 vs 0.42±0.05) , and the activity of GSH-Px[ (33.65±5.64) U/mg vs (8.42±1.87) U/ mg] and SOD [ (45.96±7.83) U/mg vs (13.65±4.34) U/ mg]were decreased, with the difference statistically significant (all P < 0.05) . Compared with the model group, the apoptotic rate of cardiomyocytes in the middle and high dose propofol group[ (34.24±4.28) ﹪ vs (19.44±3.53) ﹪, (13.61±2.29) ﹪], Ac- Foxo1 expression (2.21±0.25 vs 1.50±0.19, 1.16±0.17) , MDA content [ (12.64±2.10) nmol/ mg vs (9.24±1.02) nmol/mg, (7.16±0.87) nmol/ mg] and the levels of TNF-α [ (85.37± 10.41) pg/ mg vs (58.82±5.43) pg/ mg, (42.15±7.38) pg/ mg], IL-1β [ (57.82±7.36) pg/ mg vs 36.58±6.12) pg/ mg, (26.75±5.34) pg/ mg], and IL-6 [ (50.76±6.28) pg/ mg vs (35.26±4.99) pg/ mg, (23.51±4.32) pg/ mg] were reduced; Sirt1 expression (0.42±0.05 vs 0.65±0.07, 0.86±0.09) , and the activity of GSH-Px[ (8.42±1.87) U/ mg vs (20.45±2.86) U/ mg, (26.26±3.03) U/mg] and SOD [ (13.65±4.34) U/mg vs (24.62±4.19) U/ mg, (32.95±4.13) U/ mg]were all increased in a certain dose-dependent manner, and the difference was statistically significant (all P < 0.05) .

Conclusion

Propofol can increase the antioxidant capacity of myocardial cells in rats with intestinal ischemia-reperfusion injury, reduce inflammation, and thus protect the myocardium from injury. Its mechanism may be related to the activation of the Sirt1/Foxo1 pathway.

Key words: Propofol, Ischemia-reperfusion injury, Myocardial injury, Silent information regulation factor 2 related enzyme 1, Forkhead transcription factor 1

Jian Lei, Changsheng Zhang, Bao Wu. Protective effect of propofol on myocardial injury and related signal pathways in rats with intestinal ischemia-reperfusion injury[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2021, 11(05): 298-304.

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Figures/Tables 7

References 22

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分组	动物数	Sirt1/β-actin	Ac-Foxo1/β-actin
假手术	6	1.15±0.17	0.80±0.14
模型	6	0.42±0.05^a	2.21±0.25^a
低剂量丙泊酚	6	0.49±0.04^a	1.93±0.22^a
中剂量丙泊酚	6	0.65±0.07^abc	1.50±0.19^abc
高剂量丙泊酚	6	0.86±0.09^abcd	1.16±0.17^abcd
F值		57.411	45.590
P值		< 0.001	< 0.001

分组	动物数	Sirt1/β-actin	Ac-Foxo1/β-actin
假手术	6	1.15±0.17	0.80±0.14
模型	6	0.42±0.05^a	2.21±0.25^a
低剂量丙泊酚	6	0.49±0.04^a	1.93±0.22^a
中剂量丙泊酚	6	0.65±0.07^abc	1.50±0.19^abc
高剂量丙泊酚	6	0.86±0.09^abcd	1.16±0.17^abcd
F值		57.411	45.590
P值		< 0.001	< 0.001

分组	动物数	MDA （nmol/mg）	GSH-Px （U/mg）	SOD （U/mg）
假手术	6	4.09±0.81	33.65±5.64	45.96±7.83
模型	6	12.64±2.10^a	8.42±1.87^a	13.65±4.34^a
低剂量丙泊酚	6	11.35±0.86^a	13.37±2.95^a	16.21±3.76^a
中剂量丙泊酚	6	9.24±1.02^abc	20.45±2.86^abc	24.62±4.19^abc
高剂量丙泊酚	6	7.16±0.87^abcd	26.26±3.03^abcd	32.95±4.13^abcd
F值		45.643	49.231	40.421
P值		< 0.001	< 0.001	< 0.001

分组	动物数	MDA （nmol/mg）	GSH-Px （U/mg）	SOD （U/mg）
假手术	6	4.09±0.81	33.65±5.64	45.96±7.83
模型	6	12.64±2.10^a	8.42±1.87^a	13.65±4.34^a
低剂量丙泊酚	6	11.35±0.86^a	13.37±2.95^a	16.21±3.76^a
中剂量丙泊酚	6	9.24±1.02^abc	20.45±2.86^abc	24.62±4.19^abc
高剂量丙泊酚	6	7.16±0.87^abcd	26.26±3.03^abcd	32.95±4.13^abcd
F值		45.643	49.231	40.421
P值		< 0.001	< 0.001	< 0.001

分组	动物数	TNF-α	IL-1β	IL-6
假手术	6	19.26±3.48	9.53±1.14	8.49±2.03
模型	6	85.37±10.41^a	57.82±7.36^a	50.76±6.28^a
低剂量丙泊酚	6	74.69±6.35^a	49.61±7.97^a	44.58±5.72^a
中剂量丙泊酚	6	58.82±5.43^abc	36.58±6.12^abc	35.26±4.99^abc
高剂量丙泊酚	6	42.15±7.38^abcd	26.75±5.34^abcd	23.51±4.32^abcd
F值		84.622	58.711	71.612
P值		< 0.001	< 0.001	< 0.001

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