MMP2 and MMP9 contribute to lung ischemia-reperfusion injury via promoting pyroptosis in mice.

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is a cause of poor prognosis in several lung diseases and after lung transplantation. In LIRI, matrix metalloproteinases and pyroptosis indicators change in parallel, both of them involvement of inflammatory modulation, but it is unclear whether they are related to each other. METHODS: We analyzed the matrix metalloproteinases (MMPs) changes from RNA sequencing (RNA-Seq) data of human transplantation and rat ischemia-reperfusion lung tissues in the Group on Earth Observations (GEO) database. Then established the mouse LIRI model to validate the changes. Further, the severity of lung injury was measured after intervening the matrix metalloproteinases changes with their selective inhibitor during Lung ischemia-reperfusion. Meanwhile, lung, pyroptosis was assessed by assaying the activity of Caspase-1 and interleukin 1ß (IL-1ß) before and after intervening the matrix metalloproteinases changes. RESULTS: The RNA-Seq data revealed that matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9) mRNA expression was elevated both in human lung transplantation and rat lung ischemia-reperfusion tissues, consistent with the change in our mouse model. At the same time, the activity of Caspase-1 and IL-1ß were increased after LIRI. While, the lung injury was attenuated for the use of MMP2 and MMP9 selective inhibitor SB-3CT. Likewise, lung pyroptosis alleviated when treatment the mice with SB-3CT in LIRI. CONCLUSION: We conclude that MMP2 and MMP9 are involved in the process of LIRI, the mechanism of which is related to the promotion of lung pyroptosis.

Comparison of the perioperative outcomes in antero-superior mediastinal tumor resection performed by transcervical resection and video-assisted thoracoscopic surgery.

BACKGROUND: It remains controversial that whether transcervical resection (TC) was associated with better outcomes than video-assisted thoracoscopic surgery (VATS) in the treatment of antero-superior mediastinal tumors. We aimed to compare the safety and reliability between TC and VATS. METHODS: Between 2010 and 2012, 80 consecutive patients underwent antero-superior mediastinal tumor resection via TC (n=31) or VATS (n=49). Perioperative outcomes were compared. A propensity score-matched analysis was performed to control the potential confounders. RESULTS: A total of 41 men and 39 women with median age of 52.5 years were enrolled. No patient died during the perioperative course. After propensity matching, TC group was associated with less intraoperative blood loss (35.1±18.7 vs. 93.7±136.1 mL, P=0.034), less postoperative drainage (65.6±76.8 vs. 335.0±154.9 mL, P<0.001), shorter length of postoperative hospital stay (3.2±1.2 vs. 4.1±1.3 days, P=0.003) and less hospitalization expense (22,252.3±4,761.7 vs. 26,514.2±4,052.8 CNY, P=0.002) compared to VATS group. One patient with VATS was converted to open surgery due to intraoperative vessels damage. The postoperative complication was null in TC group while it was 6.1% (n=3) in VATS group (P=0.279), including 1 case of prolonged chest tube drainage and 2 cases of recurrent laryngeal nerve injury. CONCLUSIONS: TC for antero-superior mediastinal tumors is a safe procedure with better perioperative outcomes compared to VATS.