Oxidative Medicine and Cellular Longevity ID:8787392 (2017）
Overexpression of Brg1 Alleviates Hepatic Ischemia/Reperfusion-Induced Acute Lung Injury through Antioxidative Stress Effects
Jun Cai、Ziqing Hei
The experimental protocols and design were approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Eight- to ten-week-old C57BL/6 male mice were used. Animal care was conducted in accordance with the Guidelines of Sun Yat-sen University for Animal Experimentation. Cytomegalovirus-transgenic Brg1-overexpressing (CMV-Brg1) mice (Cyagen Biosciences, ID: TGBS130618AG1, USA) with the C57BL/6 background were used to generate CMV-Brg1 and wild-type (WT) littermates. As described previously , genotyping was performed by polymerase chain reaction using genomic DNA extracted from a tail snip. The mice were randomly assigned into five groups (n = 8 per group) in the initial intervention model establishment study, which included sham-operated as well as 3, 6, 12, and 24 h reperfusion groups. Subsequent in vivo studies were performed using the 6 h reperfusion HIR model. Both the CMV-Brg1 and WT mice were then randomly assigned into two groups (n = 5 per group): sham-operated group (sham) and HIR group.After the process of HIR, pathological damage was detected in the lungs (Figure 1(a)), including increased alveolar damage, perivascular and peribronchial edema, alveolar wall capillary hyperemia, and pulmonary interstitial inflammatory cell infiltration. It reached a peak at 6 h after reperfusion (Figure 1(a)), as reflected by the significant increase in pathological scores (Figure 1(b)), and then was restored gradually to normal.As shown in Figures 1(c) and 1(d), the changes of ROS and 8-isoprostane levels in lung tissues were consistent with lung pathological damage. Similarly, the Brg1 protein expression in lung tissue began to decline after reperfusion, significantly reduced at 3 h and 6 h (P < 0.01 versus the Sham group), reached a minimum at 6 h, and then gradually increased at 12 h and 24 h (Figure 1(e)). Nrf2 protein expression in the lung tissue did not significantly change within the first 6 h after reperfusion, but it increased significantly at 12 h and 24 h after reperfusion (Figure 1(f)).The authors acknowledge Medjaden Bioscience Limited for the scientific editing and proofreading of this manuscript. This study was partly supported by grants from the Natural Science Foundation of China (no. 81372090, no. 81571926, no. 81501695, and no. 81601724) and key project of the Natural Science Foundation of Guangdong Province, China (Grant no. S2011020002780).