Protective effect of remifentanil on myocardial ischemia-reperfusion injury through Fas apoptosis signaling pathway

Z.-JU. Qu, Z.-JI. Qu, H.-B. Zhou, C.-S. Xu, D.-Z. Zhang, G. Wang

Department of Anesthesia, Beijing Jishuitan Hospital, Beijing, China. drgengwang@163.com

---

• Pharmacology

OBJECTIVE: The aim of this study was to investigate the protective effect of remifentanil (RFT) on myocardial ischemia-reperfusion (IR) injury through Fas apoptosis signaling pathway.

MATERIALS AND METHODS: A total of 36 Sprague-Dawley (SD) rats were randomly divided into 3 groups, including the sham operation (Sham) group, IR model (IR) group and RFT pretreatment (RFT) group, with 12 rats in each group. Myocardial tissues of rats in each group were collected. Hematoxylin and eosin (H&E) staining was used to examine the pathological differences of the myocardium in the three groups. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD) and malondialdehyde (MDA) in the serum of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to detect the apoptosis level of myocardial cells in each group. Furthermore, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were applied to measure the mRNA and protein expression levels of Fas and its pathway indexes, respectively.

RESULTS: Compared with the Sham group, LDH and CK activities and MDA level in the IR group were significantly increased, whereas the level of SOD was remarkably decreased (p<0.05). Compared with the IR group, RFT pretreatment could significantly reduce the release of LDH and CK-muscle/brain (CK-MB), increase SOD level and decrease MDA level (p<0.05). TUNEL results manifested that the apoptosis rate of myocardial cells in the IR group was markedly increased than that of the Sham group (p<0.05). Meanwhile, the apoptosis rate of myocardial cells in the RFT group was notably decreased when compared with that of the IR group (p<0.05). ELISA results demonstrated that the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) proteins in the RTF group were significantly lower than those of the IR group (p<0.05). RT-PCR and Western blotting results indicated that the expressions of Fas, Fas ligand (FasL), and Fas-associated protein with death domain (FADD) in IR and RFT groups were significantly higher than those of the Sham group (p<0.05). However, RTF pretreatment could markedly reduce the levels of Fas, FasL, and FADD (p<0.05).

CONCLUSIONS: RFT can reduce the apoptosis of myocardial cells as well as IR-induced oxidative stress and inflammation by inhibiting the Fas/FasL signal transduction pathway.

Free PDF Download