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注射通过调节基质金属蛋白酶/金属蛋白酶组织抑制因子比例的平衡减轻脂多糖诱导的急性肺损伤。

Injection Alleviates LPS-Induced Acute Lung Injury by Adjusting the Balance of MMPs/TIMPs Ratio.

作者信息

Chen Guobing, Ge Dandan, Zhu Bizhen, Shi Huixuan, Ma Qilin

机构信息

Department of Paediatrics, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.

School of Medicine, Xiamen University, Xiamen 361003, China.

出版信息

Evid Based Complement Alternat Med. 2020 Jul 20;2020:9617081. doi: 10.1155/2020/9617081. eCollection 2020.

Abstract

injection (SMI) is a classical traditional Chinese medicine, which plays an active role in the treatment of many diseases such as promoting blood circulation, removing blood stasis, reducing inflammatory reaction, and improving acute lung injury (ALI). Previous studies have shown that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the pathophysiological process of ALI. However, the relationship between SMI and MMPs/TIMPs remains unclear. In this study, Wistar rats were randomly divided into control group (NC), group (SM), lipopolysaccharide group (LPS), and treatment group (Tsm). The four groups were subdivided into four time points (2, 6, 12, and 24 hours), and specimens were collected after animal sacrifice at each time point. Serum TNF- and IL-6 levels were detected by ELISA. The degree of lung injury was determined by lung tissue hematoxylin-eosin staining, lung wet/dry weight (W/D) ratio, and lung permeability index. The changes in lung MMPs/TIMPs protein and mRNA were detected by Western blot and real-time quantitative PCR. The results showed that rats injected with LPS experience acute lung injury, and the ratio of MMPs/TIMPs in lung tissues increased gradually with time. In the Tsm group, the ratio of MMPs/TIMPs decreased gradually, and likewise, the balance was gradually restored, while indicators related to lung injury were gradually declined. These data suggest that SMI alleviates LPS-induced acute lung injury; this protective effect may be related to regulation of the balance of MMPs/TIMPs ratio.

摘要

丹参注射液(SMI)是一种经典的中药,在治疗多种疾病如促进血液循环、活血化瘀、减轻炎症反应及改善急性肺损伤(ALI)等方面发挥着积极作用。以往研究表明,基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)参与ALI的病理生理过程。然而,SMI与MMPs/TIMPs之间的关系仍不清楚。本研究中,将Wistar大鼠随机分为对照组(NC)、丹参组(SM)、脂多糖组(LPS)和丹参治疗组(Tsm)。四组再细分为四个时间点(2、6、12和24小时),在每个时间点处死动物后采集标本。采用酶联免疫吸附测定法(ELISA)检测血清肿瘤坏死因子(TNF-)和白细胞介素-6(IL-6)水平。通过肺组织苏木精-伊红染色、肺湿/干重(W/D)比值及肺通透性指数来确定肺损伤程度。采用蛋白质印迹法(Western blot)和实时定量聚合酶链反应(real-time quantitative PCR)检测肺组织中MMPs/TIMPs蛋白和mRNA的变化。结果显示,注射LPS的大鼠出现急性肺损伤,肺组织中MMPs/TIMPs的比值随时间逐渐升高。在Tsm组中,MMPs/TIMPs的比值逐渐降低,同样,平衡逐渐恢复,同时与肺损伤相关的指标也逐渐下降。这些数据表明,SMI可减轻LPS诱导的急性肺损伤;这种保护作用可能与调节MMPs/TIMPs比值的平衡有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8c8/7387992/afa6765bf9af/ECAM2020-9617081.001.jpg

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