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Application of TLR4 excited exosome or exosome preparation in preparation of medicine for preventing and treating radiation-induced lung injury

A radiation-induced lung injury and exosome technology, applied in the field of medicine, can solve the problems of not being able to clarify the radiation protection effect of TLR4 agonists and restricting the practical application of TLR4 agonists, so as to reduce the degree of apoptosis and DNA damage, and reduce the proliferation activity Reduced, high clinical application value effect

Pending Publication Date: 2022-07-29
THE FIRST MEDICAL CENT CHINESE PLA GENERAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, current studies cannot clarify the specific mechanism by which TLR4 agonists play a role in radiation protection, which seriously restricts the practical application of TLR4 agonists in clinical practice.
However, there are no related reports in the prior art that TLR4-activated exosome preparations can prevent and treat radiation-induced lung injury

Method used

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  • Application of TLR4 excited exosome or exosome preparation in preparation of medicine for preventing and treating radiation-induced lung injury
  • Application of TLR4 excited exosome or exosome preparation in preparation of medicine for preventing and treating radiation-induced lung injury
  • Application of TLR4 excited exosome or exosome preparation in preparation of medicine for preventing and treating radiation-induced lung injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Clone formation experiments

[0032] (1) Grouping and corresponding processing methods:

[0033] Mouse macrophage RAW264.7 cells were selected and cultured in a cell incubator for 12 hours, then the culture medium was collected and collected by centrifugation as the culture medium of the RAWsup treatment group;

[0034] Select mouse macrophage RAW264.7, add MPLA (1 µg / mL) to the medium, and after culturing for 12 hours, collect the medium and collect it by centrifugation as the medium of the (MPLA+RAW) sup treatment group;

[0035] Medium plus MPLA (1µg / mL) was used as MPLA treatment group medium;

[0036] The normal control group (NC) was the untreated normal medium (DMEM medium).

[0037] (2) Experimental steps:

[0038] Four groups of different numbers of MLE-12 cells (400, 800, 1600, 3200) were cultured for 12 hours, and then the four different treatments shown in (1) were performed in each number of MLE-12 cell culture medium. , 0Gy, 2Gy, 4Gy, 8Gy were carried ...

Embodiment 2

[0041] (1) Different treatments of MLE-12 cells are the same as those in Example 1(1).

[0042] (2) The cultured MLE-12 cells were subjected to the above four treatments respectively, 0Gy and 8Gy irradiation were performed after 12 hours, the normal medium (DMEM medium) was replaced after irradiation, and the cells were cultured for 48 hours for flow cytometry apoptosis. detection, the results are image 3 and Figure 4 .

[0043] It can be seen that the (MPLA+RAW) sup treatment group significantly reduced the apoptosis of cells after irradiation compared with the other three groups, indicating that MPLA reduced the MLE after irradiation by stimulating macrophage TLR4 to stimulate the exosome preparation secreted by macrophages -12 Apoptosis.

Embodiment 3

[0045] (1) Different treatments of MLE-12 cells are the same as those in Example 1(1).

[0046] (2) The cultured MLE-12 cells were subjected to the above four treatments respectively, 8Gy irradiation was performed after 12 hours, and the cells were collected at the 0th, 1st, and 8th hours of irradiation for γ-H2AX Western Blot detection, and the results were as follows Figure 5 and Image 6 .

[0047] It can be seen that the exosome preparation produced after activation of macrophage TLR4 alleviates DNA double-strand breaks in irradiated MLE-12 cells.

[0048] All experiments in Examples 1-3 of the present invention were repeated more than 3 times, and the results were expressed as ±S. Use SPSS25.0 software statistical software to carry out t test on relevant data, with P<0.05 as a significant difference.

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Abstract

The invention relates to application of a TLR4 excited exosome or an exosome preparation in preparation of a medicine for preventing and treating radiation-induced lung injury, and belongs to the technical field of medicines. The invention provides an application of a TLR4 excited exosome or an exosome preparation in preparation of a medicine for preventing and treating radiation-induced lung injury, the TLR4 excited exosome or the exosome preparation is generated after macrophage TLR4 is activated by an agonist, belongs to exosomes generated by a human body, and has no tissue toxicity. Tests prove that the TLR4-excited exosome or the exosome preparation can remarkably relieve the reduction of the proliferation activity of radiation-induced pulmonary epithelial cells and reduce the apoptosis of the pulmonary epithelial cells and the damage degree of DNA after radiation, which shows that the TLR4-excited exosome or the exosome preparation has the uniqueness in the protection of ionizing radiation-induced pulmonary injury, and the TLR4-excited exosome or the exosome preparation can be used for treating the radiation-induced pulmonary injury caused by ionizing radiation-induced pulmonary injury caused by the ionizing radiation-induced pulmonary injury caused by the ionizing radiation-induced pulmonary injury caused by the ionizing radiation-induced pulmonary injury. The clinical application value is extremely high.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of TLR4-activated exosomes or exosome preparations in the preparation of medicines for preventing and treating radiation-induced lung injury. Background technique [0002] Normal lung tissue is one of the most sensitive tissues to ionizing radiation. The human body is very easy to cause radiation lung damage in the case of nuclear energy field operations and chest radiotherapy. Radiation lung injury includes early radiation pneumonitis and late radiation pulmonary fibrosis, the pathogenesis of which is still not fully understood. At present, it is believed that ionizing radiation can directly cause damage to biological macromolecules such as DNA in lung tissue cells, and indirectly cause a large amount of free radicals. Both of them can lead to the release of various cytokines and growth factors by promoting oxidative stress, vascular damage, and inflammatory re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/15A61K31/7024A61P11/00A61P39/00
CPCA61K35/15A61K31/7024A61P11/00A61P39/00A61P43/00A61P39/02
Inventor 雷霄曲宝林郭兴东杜乐辉黄祥马娜饶乐谭鑫
Owner THE FIRST MEDICAL CENT CHINESE PLA GENERAL HOSPITAL
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