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Minocycline attenuates oxidative and inflammatory injury in a intestinal perforation induced septic lung injury model via down-regulating lncRNA MALAT1 expression
International Immunopharmacology ( IF 4.8 ) Pub Date : 2021-09-22 , DOI: 10.1016/j.intimp.2021.108115
Ning Cui 1 , Yong Liang 2 , Junyu Wang 2 , Bo Liu 2 , Bing Wei 2 , Yu Zhao 1
Affiliation  

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-α, IL-1β, IL-6, PGE2, MDA, NF-κB, 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-α, IL-6, IL-1β, PGE2 and MDA in lung tissues of the mice. Mechanistically, MINO exerted the effects of anti-inflammation and anti-oxidative stress through down-regulating the expression of MALAT1 and regulating Nrf2/Keap1 and NF-κB signaling pathways.

Conclusion

MINO represses oxidative stress and inflammatory response during sepsis-induced ALI via down-regulating MALAT1 expression, and it has the potential to treat septic ALI.



中文翻译:

米诺环素通过下调 lncRNA MALAT1 表达减轻肠穿孔诱导的脓毒性肺损伤模型中的氧化和炎症损伤

背景

氧化应激和炎症反应在急性肺损伤 (ALI) 中起重要作用。尽管米诺环素 (MINO) 具有抗炎作用,是治疗炎症性疾病的有希望的候选药物,但 MINO 对脓毒症期间 ALI 的影响仍不清楚。

方法

本研究建立了肠穿孔小鼠模型。C57BL/6 小鼠接受盲肠结扎和穿刺 (CLP) 以诱导脓毒症相关的 ALI。在 CLP 后 24 小时,使用 MINO 以不同剂量(阴性对照,分别为 20 mg/kg、50 mg/kg 和 100 mg/kg)腹腔注射治疗小鼠。通过病理检查评估肺损伤的严重程度,计算肺湿/干重比来评估肺水肿的严重程度。ELISA、化学比色法、Western blot或qRT-PCR检测小鼠肺组织中TNF-α、IL-1β、IL-6、PGE2、MDA、NF-κB、Nrf2、Keap1和lncRNA MALAT1水平的变化.

结果

MINO以剂量依赖性方式改善CLP诱导的小鼠肺水肿和肺损伤。MINO给药可显着下调小鼠肺组织中TNF-α、IL-6、IL-1β、PGE2和MDA的表达。机制上,MINO 通过下调 MALAT1 的表达和调节 Nrf2/Keap1 和 NF-κB 信号通路发挥抗炎和抗氧化应激的作用。

结论

MINO 通过下调 MALAT1 表达抑制脓毒症诱导的 ALI 期间的氧化应激和炎症反应,具有治疗脓毒症 ALI 的潜力。

更新日期:2021-09-23
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