Minocycline attenuates oxidative and inflammatory injury in a intestinal perforation induced septic lung injury model via down-regulating lncRNA MALAT1 expression

Background: Oxidative stress and inflammatory responses play an important role in acute lung injury (ALI). Although minocycline (MINO) has anti-inflammatory effects and is a promising candidate in treating inflammatory diseases, the effect of MINO on ALI during sepsis is still unclear. Methods: In the present study, a mouse model with intestinal perforation was established. C57BL/6 mice received cecal ligation and puncture (CLP) to induce sepsis-associated ALI. MINO was used to treat the mice via intraperitoneal injection at different doses (negative control, 20 mg/kg, 50 mg/kg and 100 mg/kg, respectively) 24 h after CLP. The severity of lung injury was evaluated by pathological examination, and lung wet / dry weight ratio was calculated to evaluate the severity of pulmonary edema. The changes of TNF-alpha, IL-1 beta, IL-6, PGE2, MDA, NF Kappa B, Nrf2, Keap1 and lncRNA MALAT1 levels in lung tissues of the mice were detected with ELISA, chemical colorimetry, Western blot or qRT-PCR. Results: MINO ameliorated the lung edema and lung injury of the mice induced by CLP in a dose-dependent manner. MINO administration could significantly down-regulate expressions of TNF-alpha, IL-6, IL-1 beta, PGE2 and MDA in lung tissues of the mice. Mechanistically, MINO exerted the effects of anti-inflammation and antioxidative stress through down-regulating the expression of MALAT1 and regulating Nrf2/Keap1 and NF-Kappa B signaling pathways. Conclusion: MINO represses oxidative stress and inflammatory response during sepsis-induced ALI via downregulating MALAT1 expression, and it has the potential to treat septic ALI.

Automated summary

MINO can ameliorate sepsis-induced lung edema and injury by regulating the NF-Kappa B and Nrf2/Keap1 signaling pathways, suppressing inflammation and oxidative stress responses. MINO also exerts these effects by downregulating MALAT1 expression.