Korean J Physiol Pharmacol.  2014 Feb;18(1):67-72. 10.4196/kjpp.2014.18.1.67.

Naloxone Postconditioning Alleviates Rat Myocardial Ischemia Reperfusion Injury by Inhibiting JNK Activity

• Xia A
• Xue Z
• Wang W
• Zhang T
• Wei T
• Sha X
• Ding Y
• Zhou W

• KMID: 2285493
• DOI: http://doi.org/10.4196/kjpp.2014.18.1.67

Abstract

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p< 0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p< 0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.

Keyword

Cell apoptosis; c-Jun N-terminal kinases (JNK); Ischemia reperfusion; Naloxone

MeSH Terms

Animals
Apoptosis
Blotting, Western
Humans
In Situ Nick-End Labeling
Ischemia
JNK Mitogen-Activated Protein Kinases
Male
Myocardial Ischemia*
Myocytes, Cardiac
Naloxone*
Rats*
Rats, Sprague-Dawley
Reperfusion Injury*
Reperfusion*
JNK Mitogen-Activated Protein Kinases
Naloxone

Figure

• 

  Fig. 1 Pathological and morphological effects of naloxone postconditioning on MIRI rats (HE staining, ×400). (A) Sham group, (B) IR group, (C) Nal M group. Sham group, shamoperated control group; IR, 30 min ischemia prior to 2 h reperfusion; Nal M, medium-dose naloxone group (1.0 mg/kg).

• 

  Fig. 2 Effect of naloxone postconditioning on p-JNK protein expression of MIRI rats. **Compared with sham group: p<0.01; ##Compared with IR group: p<0.01. Sham group:sham-operated control; IR, 30 min ischemia prior to 2 h reperfusion; Nal L, Low-dose naloxone group (0.5 mg/kg); Nal M, Medium-dose naloxone group (1.0 mg/kg); Nal H, High-dose naloxone group (2.0 mg/kg).

• 

  Fig. 3 Effect of naloxone postconditioning on cell apoptosis of MIRI rats (×200). (A) Sham group, (B) IR group, (C) Nal L group, (D) Nal M group, (E) Nal H group. Sham group, sham-operated control; IR, 30 min ischemia prior to 2 h reperfusion; Nal L, Low-dose naloxone group (0.5 mg/kg); Nal M, Medium-dose naloxone group (1.0 mg/kg); Nal H, High-dose naloxone group (2.0 mg/kg).

• 

  Fig. 4 Effect of naloxone postconditioning on the apoptosis indices of MIRI rats (mean±SD, n=8). **Compared with sham group: p<0.01; ##Compared with IR group: p<0.01. Sham, Sham-operated control; IR, 30 min ischemia prior to 2 h reperfusion; Nal L, Low-dose naloxone group (0.5 mg/kg); Nal M, Medium-dose naloxone group (1.0 mg/kg); Nal H, High-dose naloxone group (2.0 mg/kg).

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