[Effects of lipoxinA4 on endoplasmic reticulum stress during myocardial ischemia reperfusion injury in rats].

OBJECTIVE

To explore the protective effect of lipoxin (LX)A4 during myocardial ischemia reperfusion injury (MIRI) and discuss the molecular mechanism of excessive endoplasmic reticulum stress (ERS) in rats.

METHODS

Seventy-two male SD rats were divided into 6 groups, according to random number table, 12 in each group: sham operation group (group sham)1, 2: injected with normal saline (NS) 2 ml/kg before and after coronary artery threading. MIRI group (group I/R)1, 2: injected with NS 2 ml/kg before and after MIRI. Group LX1, LX2: injected with LXA4 100 µg/kg in 2 ml/kg NS before and after MIRI treatment. After the rat MIRI model was established, the serum concentrations of troponin I (cTnI) were measured in each group before open-chest operation (T1) and at the end of the experiment (T2). Besides, expressions of GRP-78, caspase-12 protein and mRNA were test. At the same time, myocardial cell apoptosis, the myeloperoxidase (MPO), superoxide dismutase (SOD) activation and malondialdehyde (MDA) content were detected while the HE and ultrastructural changes of cardiac muscle were observed.

RESULTS

The expression levels of GRP-78, caspase-12 protein and mRNA, apoptotic index, serum cTnI concentrations (T2) and MPO, SOD activation, MDA content were all significantly higher in groups I/R and LX than those in group sham 1 and sham 2 (all P < 0.05). The expression levels of GRP-78, caspase-12 protein in group LX1 (compared with group I/R1) and in group LX2 (compared with group I/R2) were all significantly lower (all P < 0.05). Besides, the expression of GRP-78, caspase-12 mRNA in group LX1 were significantly less than those in group I/R1 ((0.86 ± 0.06)×10(5) vs (1.95 ± 0.65)×10(5), (12.35 ± 4.15)×10(5) vs (23.76 ± 6.57) ×10(5), both P < 0.05), so were those in groups LX2 and I/R2 ((0.64 ± 0.05)×10(5) vs (2.36 ± 0.57)×10(5), (7.04 ± 0.81)×10(5) vs (26.49 ± 6.82)×10(5), both P < 0.05). The apoptotic index, the serum concentrations of cTnI (T2), MPO activation and MDA content were all significantly lower in group LX1 than those in group I/R1 (34.6% ± 5.7% vs 52.5% ± 6.4%, (293 ± 22) vs (581 ± 44) ng/L, (176 ± 47) vs (331 ± 94) U/g tissue, (1549 ± 238) vs (2403 ± 439) nmol/g protein, both P < 0.05), so were those in groups LX2 and I/R2(26.5% ± 4.6% vs 54.8% ± 6.3%, (207 ± 29) vs (593 ± 61) ng/L, (99 ± 24) vs (329 ± 92) U/g tissue, (1055 ± 237) vs (2422 ± 518) nmol/g protein, all P < 0.05). In addition, the activity of SOD in groups LX1 and LX2 were both significantly higher respectively than those in groups I/R1 and I/R2 (both P < 0.05). Moreover, compared with groups I/R1 and I/R2, the neutrophils infiltration were significantly less than those in groups LX1 and LX2 respectively, and the ultrastructure damage were also much milder.

CONCLUSIONS

Before and after MIRI, application of LXA4 may significantly inhibit neutrophil infiltration and attenuate myocardial oxidative injury. LXA4 play its role in myocardial protection via down-regulating the expression of GRP-78, caspase-12 and the inhibition of excessive ERS.