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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | 25 gender and age matching healthy controls |
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| ARDS group 1 | 100 ARDS patients at the time of check in hospital |
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| ARDS group 2 | 100 ARDS patients at the time of 24h after check in hospital |
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| ARDS group 3 | 100 ARDS patients at the time of 48h after check in hospital |
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| ARDS group 4 | 100 ARDS patients at the time of 72h after check in hospital |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| no intervention | Other | no intervention |
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| Measure | Description | Time Frame |
|---|---|---|
| The expression of lncRNA NEAT1 in blood and BALF in all groups | 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 | 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 | 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 | 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 | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| The differences and correlation of the expressions of lncRNA NEAT1、miR-27b and Nrf2 in the groups | 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. |
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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).
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We included ARDS patients from RICU、EICU、SICU、CCU in Beijing Anzhen hospital between 2020 and 2022
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases | Beijing | Beijing Municipality | 100029 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22797452 | Background | ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. | |
| 29466596 | Background | Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018 Feb 20;319(7):698-710. doi: 10.1001/jama.2017.21907. |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D010335 | Pathologic Processes |
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Blood and BALF will be stored at -70˚C
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 | Record the time of mechanical ventilation of patients in ARDS groups | up to28 day |
| The severity of ARDS patients in ARDS groups | 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 | Record the mortality in 28 days of ARDS patients | 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 | 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 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |