Application of mpla in the preparation of drugs for the prevention and treatment of intestinal damage caused by ionizing radiation

A technology of ionizing radiation and intestinal damage, applied in the field of medicine, to increase the survival time, reduce the apoptosis of intestinal crypt cells, and achieve the effect of safe and convenient medication

Active Publication Date: 2020-09-29
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the prior art, there is no relevant report on the prevention and treatment effect of MPLA on intestinal radiation injury

Method used

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  • Application of mpla in the preparation of drugs for the prevention and treatment of intestinal damage caused by ionizing radiation
  • Application of mpla in the preparation of drugs for the prevention and treatment of intestinal damage caused by ionizing radiation
  • Application of mpla in the preparation of drugs for the prevention and treatment of intestinal damage caused by ionizing radiation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Firstly, a mouse model of radiation-induced intestinal injury was established. Female C57BL / 6 mice aged 6-8 weeks were selected and randomly divided into three groups: the irradiation group (15Gy) with 8 mice and the MPLA administration group (15Gy+MPLA) 12 hours before irradiation. )8 rats and 8 rats in the control group; 60 Coγ-rays were irradiated to the abdomen of mice once, and the absorbed dose of mice was 15Gy. MPLA (1 μg / mouse in 0.1 ml saline) or saline (0.1 ml / mouse) was delivered to the corresponding groups by intragastric administration. Mice (saline or MPLA pretreated) were observed and recorded every morning and evening for 30 days after radiation exposure. The activity of the mice in the irradiation group decreased significantly one day after irradiation, and the food intake decreased significantly, while the activity of the mice in the MPLA-administered group before irradiation was significantly better than that of the irradiation control group. The su...

Embodiment 2

[0032] (1) The radiation-induced intestinal injury mouse model is the same as that in Example 1;

[0033](2) Feeding of mice: Place the mice in a cage with daily change of litter at 25±1°C to ensure sufficient water and food.

[0034] (3) Female C57BL / 6 mice aged 6-8 weeks were selected and randomly divided into two groups: 8 mice in the irradiation group (15Gy) and 8 mice in the MPLA administration group (15Gy+MPLA) 12 hours before irradiation. MPLA (1 μg / mouse in 0.1 ml saline) or saline (0.1 ml / mouse) was delivered to the corresponding groups by intragastric administration. At different time points after radiation exposure (1 day, 3 days, 7 days), the mice were sacrificed, and the small intestine tissues were taken, fixed, embedded in wax blocks, sectioned and stained with HE. as attached figure 2 As shown, ionizing radiation obviously caused the breakage and shedding of small intestinal villi in mice; the MPLA administration group before irradiation (irradiation + MPLA)...

Embodiment 3

[0036] (1) The radiation-induced intestinal injury mouse model is the same as that in Example 1;

[0037] (2) 6-8 weeks old female C57BL / 6 mice and TLR4-deficient mice were selected and randomly divided into six groups: ①Wild-type mice unirradiated group ②Wild-type mouse abdominal irradiation group (15Gy) ③Wild-type mice Mice were irradiated to MPLA group ④TLR4-deficient mice were not irradiated group ⑤TLR4-deficient mice abdominal irradiation group (15Gy) ⑥Wild-type mice were irradiated to MPLA group. MPLA (1 μg / mouse in 0.1 ml saline) or saline (0.1 ml / mouse) was delivered to the corresponding groups by intragastric administration. The mice were sacrificed 3 days after irradiation, and the small intestine tissues were taken, fixed, embedded in wax blocks, sectioned and immunohistochemically stained with anti-Ki-67 antibody. Ki-67 is one of the marker molecules of cell proliferation. as attached image 3 As shown, the intestinal crypts of wild-type mice in the non-irradiat...

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Abstract

The invention belongs to the technical field of medicine, and more specially discloses applications of MPLA (Monophosphoryl lipid A) in preparation of drugs used for preventing and treating ionizationradiation induced intestinal injuries. Toxic and side effect of MPLA as a drug used for preventing and treating ionization radiation induced intestinal injuries is low, curative effect on ionizationradiation induced intestinal injuries is excellent, and drug using is safe and convenient. MPLA possesses unique advantages in preventing and treating ionization radiation induced intestinal injuries,and a novel method is provided for preventing and treating ionization radiation induced intestinal injuries. Effective preventing and treating methods on intestinal radiation injuries and intestinalradiation disease are few at home and abroad, development of the methods is a key problem in the field of radioactive medicine, so that application prospect of MPLA as a drug used for preventing and treating ionization radiation induced intestinal injuries is promising.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of MPLA (glucopyranoside lipid A) in the preparation of drugs for the prevention and treatment of intestinal damage caused by ionizing radiation. Background technique [0002] With the wide application of nuclear science and technology, wartime nuclear radiation, nuclear terrorist attacks, nuclear reactor accidents in peacetime, and clinical radiotherapy for malignant tumors can all cause ionizing radiation damage to the body. The severity of damage to various tissues and organs in the body is closely related to the radiation sensitivity of each tissue. Intestinal epithelial cells are highly radiation-sensitive tissues and are one of the main targets of radiation injury, especially intestinal crypt stem cells. Ionizing radiation can rapidly induce pathological changes such as apoptosis, degeneration and necrosis in small intestinal crypt cells. The intestinal c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/7024A61P1/00A61P39/00
CPCA61K31/7024
Inventor 杨彦勇雷霄蔡建明崔建国李百龙陈媛媛刘聪高福刘哲许洋郭佳铭
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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