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姜黄素后处理通过调控miR-21/TLR4/NF-κB信号通路减轻肺损伤的机制。

The mechanism of curcumin post-treatment relieving lung injuries by regulating miR-21/TLR4/NF-κB signalling pathway.

作者信息

Zou Hai-Bo, Sun Xiao-Feng

机构信息

Department of Anaesthesiology, Affiliated Central Hospital, Shenyang Medical College, Shenyang, Liaoning Province, China.

出版信息

J Int Med Res. 2020 Nov;48(11):300060520965809. doi: 10.1177/0300060520965809.

Abstract

OBJECTIVE

To investigate the mechanism by which curcumin prevents lung injury in a rat model of limb ischaemia-reperfusion injury.

METHODS

Rats were randomized into four groups ( = 20): control group (sham group); ischaemia-reperfusion group (I/R group); curcumin group (I/R+Cur group); and inhibitor of agomir-21 group (I/R+Cur+antagomir-21 group). At 3 h after reperfusion, lung tissues were collected for histopathology and immunohistochemistry to determine the apoptosis index (AI). Lung injury score (LIS) and lung wet/dry (W/D) ratio were determined. Lung microRNA-21 (miR-21) mRNA levels were measured using reverse transcription-polymerase chain reaction. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) protein levels were measured by Western blot analysis. Tumour necrosis factor (TNF)-α and interleukin (IL)-1β levels were determined by enzyme-linked immunosorbent assays.

RESULTS

In the I/R group, the W/D, LIS, AI, miR-21 mRNA, TLR4, NF-κB p65, TNF-α and IL-1β were significantly increased and the PaO was decreased compared with the sham group. Evidence of lung injury was observed in the I/R group and this was alleviated in the I/R+Cur group. An inhibitor of miR-21 (antagomir-21) reversed the protective effects of curcumin.

CONCLUSION

Curcumin post-treatment can alleviate the lung injuries induced by limb ischaemia-reperfusion via downregulating the levels of miR-21 mRNA.

摘要

目的

探讨姜黄素预防肢体缺血再灌注损伤大鼠模型肺损伤的机制。

方法

将大鼠随机分为四组(每组n = 20):对照组(假手术组);缺血再灌注组(I/R组);姜黄素组(I/R+Cur组);以及agomir-21抑制剂组(I/R+Cur+antagomir-21组)。再灌注3小时后,收集肺组织进行组织病理学和免疫组织化学检查,以确定凋亡指数(AI)。测定肺损伤评分(LIS)和肺湿/干(W/D)比值。采用逆转录-聚合酶链反应检测肺组织微小RNA-21(miR-21)mRNA水平。通过蛋白质印迹分析测定Toll样受体4(TLR4)和核因子κB p65(NF-κB p65)蛋白水平。采用酶联免疫吸附测定法测定肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β水平。

结果

与假手术组相比,I/R组的W/D、LIS、AI、miR-21 mRNA、TLR4、NF-κB p65、TNF-α和IL-1β显著升高,而动脉血氧分压(PaO)降低。I/R组出现肺损伤证据,而I/R+Cur组肺损伤得到缓解。miR-21抑制剂(antagomir-21)可逆转姜黄素的保护作用。

结论

姜黄素治疗后可通过下调miR-21 mRNA水平减轻肢体缺血再灌注诱导的肺损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/318b/7705296/b39927072eff/10.1177_0300060520965809-fig1.jpg

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