The Mechanism of lncRNA NEAT1 in Alleviating Acute Respiratory Distress Syndrome Through miR-27b Regulated Nrf2 Pathway
2021年6月16日 更新者：Guangfa Zhu、Beijing Anzhen Hospital
The acute respiratory distress syndrome, formerly known as the acute lung injury (ARDS/ALI), is a critical illness with high mortality due to the lack of effective treatment.
The pathogenesis of ARDS/ALI has not been fully elucidated.
Nuclear factor E2-related factor 2 (Nrf2) plays a key role in regulating lung inflammation and oxidative stress which are closely related to lung injury in ARDS/ALI, but its regulatory mechanism remains unclear.
The investigator's provious study shown that microRNA-27b (miR-27b) downregulated Nrf2 to aggravate lung inflammation and histological injury.
Furthermore, in lipopolysaccharide (LPS)-induced cell (J774A.1)
inflammation model, miR-27b was upregulated while the long non-coding RNA (lncRNA) NEAT1 was downregulated, the putative binding sites of lncRNA NEAT1 and miR-27b were successfully predicted by bioinformatics approach.
Thus, the investigators propose that NEAT1 plays as a competing endogenous RNA (ceRNA) to adsorb miR-27b and liberate Nrf2, therefore, to attenuate lung inflammation and related lung injury in ARDS/ALI.
This project aims to explore the role of the lncRNA NEAT1/ mir-27b /Nrf2 signal axis in the development and treatment of ARDS/ALI in patients, as well as in LPS-induced ALI animal and cell models by using bioinformatics, molecular biology, histomorphology and clinical phenotype approaches, and to clarify the new mechanism in ARDS/ALI development and to provide new therapeutic targets.
調査の概要
詳細な説明
Collect blood and BALF from 400 ARDS patients at different time (at check-in, 24, 48 and 72 h after check-in the hospital) and 25 gender and age matching healthy controls.
Use RT-PCR to detect the expression of lncRNA NEAT1、miR-27b and Nrf2 in blood and BALF of ARDS patients and health controls.
The expressions of inflammatory and oxidative stress associated factors (NLRP3、NF-κB-P65、 p-P65、IκB、p-IκB、HO-1、NQO1、caspase-1、IL-1β、IL-6、IL-18、TNF-α) will be detected by western blot、ELISA and RT-PCR.
Moreover, flow cytometry will be adopted to measure the numbers and kinds of cells in BALF.
Then, analyze the differences of the expressions of lncRNA NEAT1、miR-27b and Nrf2 in the groups.
To explore the correlation of expressions of lncRNA NEAT1、miR-27b and Nrf2 with inflammation and oxidative stress in the groups.
Finally, to declare the relative of lncRNA NEAT1、miR-27b and Nrf2 with the time of mechanical ventilation, severity and mortality in 28 days of ARDS patients.
研究の種類
観察的
入学 (予想される)
425
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Beijing
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Beijing、Beijing、中国、100029
- Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～70年 (大人、高齢者)
健康ボランティアの受け入れ
はい
受講資格のある性別
全て
サンプリング方法
確率サンプル
調査対象母集団
We included ARDS patients from RICU、EICU、SICU、CCU in Beijing Anzhen hospital between 2020 and 2022
説明
Inclusion Criteria:
We included patients with acute respiratory distress according to 2012 ARDS Berlin new definition (Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA, 2012, 307(23):2526).
- Acute or progressive dyspnea within 1 week with identify cause;
- Chest radiograph/chest CT showed double lung infiltration, which could not be fully explained by pleural effusion, atelectasis, or nodules;
- Respiratory failure cannot be fully explained by heart failure and fluid overload;
- Hypoxemia, partial pressure of oxygen in arterial blood (PaO2)/oxygen fraction in air (FIO2) <150 mm Hg under PEEP ≥5 cm H2O, (mild ARDS: 200mmHg<PaO2/FiO2≤300mmHg, moderate ARDS: 100mmHg<PaO2/FiO2≤200mmHg, severe ARDS: PaO2/FiO2≤100mmHg);
- 18~70 years old;
- Agree to participate in the trial, and sign the informed consent.
Exclusion Criteria:
- Age less than 18 years old;
- Time of hospital stay <24 h;
- Pregnancy;
- Using V-V ECOM;
- Cardiac index <1.5L·ml.min-1.m-2;
- Pulmonary resection;
- Pulmonary embolism ;
- Refused to participate in the study.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
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Control group
25 gender and age matching healthy controls
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介入なし
|
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ARDS group 1
100 ARDS patients at the time of check in hospital
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介入なし
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ARDS group 2
100 ARDS patients at the time of 24h after check in hospital
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介入なし
|
|
ARDS group 3
100 ARDS patients at the time of 48h after check in hospital
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介入なし
|
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ARDS group 4
100 ARDS patients at the time of 72h after check in hospital
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介入なし
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The expression of lncRNA NEAT1 in blood and BALF in all groups
時間枠：up to 24 day
|
Use RT-PCR to measure the expression of lncRNA NEAT1 in blood and BALF in all groups
|
up to 24 day
|
|
The expression of miR-27b in blood and BALF in all groups
時間枠：up to 3 day
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Use RT-PCR to measure the expression of miR-27b in blood and BALF in all groups
|
up to 3 day
|
|
The expression of Nrf2 in blood and BALF in all groups
時間枠：up to 3 day
|
Use RT-PCR and Wsetern blot to measure the expression of Nrf2 in blood and BALF in all groups
|
up to 3 day
|
|
The expression of inflammatory factors(IL-1β、IL-6、IL-18、TNF-α) in blood and BALF in all groups
時間枠：up to 3 day
|
Use RT-PCR and ELISA to measure the expression of inflammatory factors(IL-1β、IL-6、IL-18、TNF-α) in blood and BALF in all groups
|
up to 3 day
|
|
The expression of oxidative stress associated factors in blood and BALF in all groups
時間枠：up to 3 day
|
Use Western blot to measure the expression of oxidative stress associated factors(NLRP3、NF-κB-P65、 p-P65、IκB、p-IκB、HO-1、NQO1、caspase-1) in blood and BALF in all groups
|
up to 3 day
|
|
The numbers and kinds of inflammatory cells in BALF and blood in all groups
時間枠：up to 3 day
|
Use flow cytometry to detect the number of inflammatory cells in BALF and blood in all groups
|
up to 3 day
|
|
The kinds of inflammatory cells in BALF and blood in all groups
時間枠：up to 3 day
|
Use flow cytometry to detect the kinds of inflammatory cells(neutrophile、macrophage、 lymphocyte) in BALF and blood in all groups
|
up to 3 day
|
|
The time of mechanical ventilation of patients in ARDS groups
時間枠：up to28 day
|
Record the time of mechanical ventilation of patients in ARDS groups
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up to28 day
|
|
The severity of ARDS patients in ARDS groups
時間枠：up to 28 day
|
Record the severity(PaO2/FiO2、OI、S/F、OSI) of ARDS patients in ARDS groups
|
up to 28 day
|
|
the mortality in 28 days of ARDS patients
時間枠：up to 28 day
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Record the mortality in 28 days of ARDS patients
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up to 28 day
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The differences and correlation of the expressions of lncRNA NEAT1、miR-27b and Nrf2 in the groups
時間枠：up to 28 day
|
Analyse the differences of the expressions of lncRNA NEAT1、miR-27b and Nrf2 in the groups, and to explore the relations between the three(lncRNA NEAT1、miR-27b and Nrf2) in different groups.
|
up to 28 day
|
|
The correlation of expressions of lncRNA NEAT1、miR-27b and Nrf2 with inflammation and oxidative stress in the groups.
時間枠：up to 28 day
|
To explore the correlation of expressions of lncRNA NEAT1、miR-27b and Nrf2 with inflammation and oxidative stress in the groups.
|
up to 28 day
|
|
The relative of lncRNA NEAT1、miR-27b and Nrf2 with the time of mechanical ventilation, severity and mortality in 28 days of ARDS patients
時間枠：up to 28 day
|
To declare the relative of lncRNA NEAT1、miR-27b and Nrf2 with the time of mechanical ventilation, severity and mortality in 28 days of ARDS patients
|
up to 28 day
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (予想される)
2021年7月1日
一次修了 (予想される)
2022年12月31日
研究の完了 (予想される)
2023年12月31日
試験登録日
最初に提出
2020年1月11日
QC基準を満たした最初の提出物
2021年6月16日
最初の投稿 (実際)
2021年6月24日
学習記録の更新
投稿された最後の更新 (実際)
2021年6月24日
QC基準を満たした最後の更新が送信されました
2021年6月16日
最終確認日
2021年6月1日
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