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. 2020 Jun 3;10(2):2045894020922125.
doi: 10.1177/2045894020922125. eCollection 2020 Apr-Jun.

Improvement of lung ischemia-reperfusion injury by inhibition of microRNA-155 via reductions in neuroinflammation and oxidative stress of vagal afferent nerve

Yan Zhou  1 , Lianjie Zhang  1 , Jingjing Guan  1 , Xin Yin  1
Affiliations

Improvement of lung ischemia-reperfusion injury by inhibition of microRNA-155 via reductions in neuroinflammation and oxidative stress of vagal afferent nerve

Yan Zhou et al. Pulm Circ. .

Abstract

Lung ischemia-reperfusion injury (LIRI) is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine the effects of inhibiting microRNA-155 on the levels of proinflammatory cytokines and products of oxidative stress in the pulmonary vagal afferent nerves and the commissural nucleus of the solitary tract (cNTS) after LIRI. A rat model of LIRI was used. ELISA method was employed to examine proinflammatory cytokines, namely, IL-1β, IL-6 and TNF-α; and key biomarkers of oxidative stress, 8-isoprostaglandin F2α (8-iso PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). In results, in the process of LIRI, the levels of microRNA-155 were amplified in the vagal afferent nerves and cNTS, and this was accompanied with increases of IL-1β, IL-6 and TNF-α; and 8-iso PGF2α and 8-OHdG. Application of microRNA-155 inhibitor, but not its scramble, attenuated the elevation of proinflammatory cytokines and amplification of 8-iso PGF2α and 8-OHdG in those nerve tissues. In conclusion, we observed the abnormalities in the pulmonary afferent pathways at the levels of the peripheral nerves and brainstem, which is likely to affect respiratory functions as LIRI occurs. Our data suggest that blocking microRNA-155 signal pathways plays a beneficial role in regulating LIRI via inhibiting responses of neuroinflammation and oxidative stress signal pathways to LIRI.

Keywords: brainstem; lung ischemia; miRNA-155; neuroinflammation; oxidative stress; vagal nerves.

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Figures

Fig. 1.
Fig. 1.
Blood oxygen and carbon dioxide; and blood pressure and heart rate after lung ischemia reperfusion injury (LIRI). Top panels: Arterial partial pressure of oxygen and arterial partial pressure of carbon dioxide of rats in sham control rats and rats with LIRI. 0 h indicates baseline before ischemia; and 1.0, 3.0 and 6.0 h indicate times after reperfusion. *P < 0.05 vs. baseline. Bottom panels: Mean arterial pressure and heart rate of sham control rats and LIRI rats before ischemia, and 1.0–6.0 h after reperfusion. There were no differences in mean arterial pressure and heart rate for baseline and at different time points after reperfusion in sham control and LIRI groups. Note that “n” indicates a total number of rats in sham control group (n = 12) and LIRI group (n = 28).
Fig. 2.
Fig. 2.
The time course for the levels of miR-155 mRNA was increased in the nodose ganglion (NG) and the commissural nucleus of the solitary tract (cNTS) after the end of LIRI procedure and the increase was stabilized 6 h after the LIRI procedure and remained at a high level. *P < 0.05 vs. its level before LIRI (baseline). Point “0” indicates before LIRI. The number of rats = 6–10 in each group.
Fig. 3.
Fig. 3.
The levels of IL-1β, IL-6 and TNF-α in the nodose ganglion (NG)/vagal nerve (top panels) and the commissural nucleus of the solitary tract (cNTS; bottom panels). The cytokines were significantly increased in LIRI rats with scramble as compared with control animals. MiR-155 inhibitor attenuated increases of those cytokines in the peripheral and central vagal afferent nerves of LIRI rats. *P < 0.05, indicated rats with LIRI with scramble (n = 16) vs. sham control rats (n = 12) and LIRI rats with miR-155 inhibitor (n = 15).
Fig. 4.
Fig. 4.
Effects of LIRI on oxidative stress signal pathways. LIRI amplified the levels of oxidative products 8-iso PGF2α and 8-OHdG in the the nodose ganglion (NG) and the commissural nucleus of the solitary tract (cNTS). As miR-155 inhibitor was infused via ICV, increases of 8-iso PGF2α and 8-OHdG were attenuated. *P < 0.05, LIRI rats with miR-155 scramble (n = 16) vs. sham control rats (n = 12) and LIRI rats with miR-155 inhibitor (n = 15).
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