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Use of miR-155 in preparation of acute lung injury prevention and treatment drugs

A technology for acute lung injury and lung injury, which is applied in the field of biomedicine and can solve problems such as expression defects and increased secretion

Active Publication Date: 2015-03-25
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Defective expression of miRNA-125a leads to increased secretion of T cell inflammatory chemokine RANTES in lupus patients[10]

Method used

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  • Use of miR-155 in preparation of acute lung injury prevention and treatment drugs
  • Use of miR-155 in preparation of acute lung injury prevention and treatment drugs
  • Use of miR-155 in preparation of acute lung injury prevention and treatment drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Example 1. miR-155 knockout mice are resistant to Pristane-induced pulmonary hemorrhage

[0071] The inventors first detected the expression level of miR-155 in the Pristane-induced acute lung injury mouse model. It was found that after intraperitoneal injection of 0.5ml Pristane for two weeks, compared with the control group, the expression of miR-155 in the lung was significantly up-regulated (see figure 2 a-b).

[0072] In order to clarify the role of miR-155 in acute lung injury, the inventors used miR-155 gene knockout mice to conduct Pristane induction experiments. It was found that mice knocked out of miR-155 had significant resistance to pulmonary hemorrhage (20% of mice developed pulmonary hemorrhage), while normal C57 mice had a disease rate as high as 80% (see figure 2 d). Compared with controls, miR-155 KO mice had intact lung structures (see figure 2 c).

Embodiment 2

[0073] Example 2. Intervention of miR-155 in vivo can prevent the occurrence of Pristane-induced pulmonary hemorrhage

[0074] In order to further clarify the role of miR-155 in the process of lung injury, the inventors used miR-155 antagomir to conduct in vivo intervention experiments.

[0075] The results showed that mice injected with miR-155antagomir (miR-155anta) had significant resistance to Pristane-induced pulmonary hemorrhage ( image 3 a-b).

[0076] In order to verify the inhibitory efficiency of miR-155 antagomir, the inventors collected RNA from different tissues and performed quantitative analysis of miR-155. It was found that, at 14 days, the expression level of miR-155 in each tissue of the mice injected with miR-155antagomir was lower than that of the antagomir negative control group and the PBS group ( image 3 c). This shows that miR-155 antagomir is effective, and the resistance of mice to pulmonary hemorrhage is indeed due to the absence of miR-155.

Embodiment 3

[0077] Example 3, miR-155 can promote the secretion of inflammatory factors in serum

[0078] It has been reported that miR-155, as a pro-inflammatory factor, can promote the expression of some inflammatory factors, such as IL-6 and TNF-a [14].

[0079] Therefore, the present inventors examined whether miR-155 deletion has an effect on the production of inflammatory cytokines in a Pristane-induced pulmonary hemorrhage model. On the 14th day of Pristane induction, different groups of serum were collected, and through the bioplex-cytokine suspension chip, the inventors found that some inflammatory factors, such as IL-1b, IL-6, TNF-a, IL-17, were induced by Pristane 14-day-old normal mice were significantly increased, while in miR-155KO mice, the expression levels of these factors were significantly reduced ( Figure 4 ).

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Abstract

The invention relates to a use of miR-155 in the preparation of acute lung injury prevention and treatment drugs. The invention discloses a close relationship between miR-155 with acute lung injury for the first time, and the miR-155 with promotes the occurrence of the acute lung injury, so downward agents of the miR-155 can be used to prevent, alleviate or treat the acute lung injury, especially acute lung hemorrhage.

Description

technical field [0001] The invention belongs to the field of biomedicine; more specifically, the invention relates to the use of miR-155 in the preparation of medicines for preventing and treating acute lung injury. Background technique [0002] Pulmonary hemorrhage is a serious complication of systemic lupus erythematosus (SLE) with a low incidence (1.9 percent) and a very high mortality rate (92 percent) [1]. Although numerous case reports describe a series of patients with diffuse pulmonary hemorrhage (DAH), its pathogenesis remains unknown. Secondly, pulmonary hemorrhage is often accompanied by inflammatory cell infiltration, immune complex deposition and other changes. The inconsistency between the literature reports and the immunopathology and clinical manifestations of pulmonary hemorrhage hinders people's research on the pathogenesis of pulmonary hemorrhage as a complication of SLE. Most of the information on tissue immunopathology is obtained by autopsy, so the me...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K48/00A61P11/00A61P29/00A61P37/02C12N15/113
Inventor 沈南黄新芳周诗雨肖春媛
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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