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Application of miR-122 and inhibitor thereof to prevention/treatment of radiation-induced brain injury

A radiation-induced brain injury, 1.mir-122 technology, applied in the field of biomedicine, can solve problems such as unsatisfactory treatment and side effects, and achieve the effects of preventing or treating radiation-induced brain injury, reducing expression, and relieving neuroinflammation damage

Active Publication Date: 2020-08-28
AFFILIATED HOSPITAL OF GUANGDONG MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] Aiming at the problems existing in the prior art, the object of the present invention is to provide a kind of application of miR-122 and its inhibitor in the prevention / treatment of radiation brain injury, To solve the problems of side effects and unsatisfactory treatment of currently commonly used radiation brain injury drugs

Method used

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  • Application of miR-122 and inhibitor thereof to prevention/treatment of radiation-induced brain injury
  • Application of miR-122 and inhibitor thereof to prevention/treatment of radiation-induced brain injury
  • Application of miR-122 and inhibitor thereof to prevention/treatment of radiation-induced brain injury

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Effect test

Embodiment 1

[0038] Such as figure 1 As shown, the relationship between miR-122-5p expression level and radiation brain injury:

[0039] The RBI model mice were constructed by irradiation dose of 30Gy (see figure 1 A), and then performed miRNA next-generation sequencing on its hippocampus. The test results indicated that miR-122 was abnormally expressed in the hippocampus of RBI mice, and the RT-qPCR verification results were consistent with the gene sequencing results (see figure 1 B~C).

[0040] Subsequently, in order to further analyze the correlation between the expression level of miR-122 and the severity of RBI, the inventors collected serum samples from 28 patients with nasopharyngeal carcinoma before radiotherapy, at the second week of radiotherapy, at the fourth week of radiotherapy, and one month after the end of radiotherapy. The expressions of S100B, miR-122 and IL-1β were detected. The results showed that the levels of S100B, miR-122 and IL-1β in patients with nasopharynge...

Embodiment 2

[0043] Such as Figure 2~4 As shown, on the basis of Example 1, the animal level intervention is carried out through nasal administration of Antagomir-122, and the behavior of mice is also tested using a water maze, wherein the specific steps of nasal administration are: dissolving Antagomir-122 in In 1mL of RNase-free water, fix the mouse with a simple mouse fixer and lie on its back, then use a pipette to add 24ul Antagomir-122 (40nmol / mL) solution dropwise, and inject the left and right nostrils alternately (1ul / time), each injection The interval is 3-5min. Hippocampal tissue was taken 24 hours after intranasal delivery, and the dynamic changes of miR-122 in hippocampus after intranasal delivery of Antagomir-122 were further analyzed using real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Among them, TRIzol can be used to extract tissue total RNA, real-time fluorescent quantitative polymerase chain reaction can be used SYBR RT-PCR kit (Takara), and co...

Embodiment 3

[0057] Such as Figure 5 As shown, miR-122-5p inhibitor inhibited radiation cell injury in vitro:

[0058] Microglial cells BV2 were transfected with AntagomiR-122, irradiated with 10Gy, and the morphology, phagocytosis and related inflammatory factors of microglial cells were analyzed. Among them, Figure 5 A is the data of adopting 50nmol and 100nmol transfection efficiency respectively; Figure 5 C is the data of 100 nmol transfection efficiency used. The results showed that miR-122 intervention ameliorated the decreased cell viability induced by irradiation (see Figure 5 A); The levels of IL-1β and IL-6 inflammatory factors induced by irradiation were significantly reduced after miR-122 intervention (see Figure 5 B), where, Figure 5 In B, immunofluorescence Iba-1 marks microglial cells, DAPI stains cell nuclei, beads are fluorescent microspheres added to cells to evaluate the phagocytosis of microglial cells, and merge represents a summary overlapping image, from wh...

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Abstract

The invention provides an application of miR-122 and an inhibitor thereof to prevention / treatment of radiation-induced brain injury. Through experimental research, the inventor finds that the expression of miR-122-5p in a radiated mouse hippocampus and a clinical nasopharyngeal cancer radiotherapy patient is significantly raised; but after intervention with the miR-122, neuroinflammation injury can be relieved in a RBI animal model, and behavior recognition can be improved; and in an in vitro cell radiation-induced injury model, restraint of the miR-122 can adjust and control microglia to tendto M2 type polarization.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of miR-122 and its inhibitors in the prevention / treatment of radiation brain injury. Background technique [0002] Radiation-induced Brain Injury (RBI) is the main dose-limiting adverse event of radiation therapy for head and neck tumors, especially nasopharyngeal carcinoma (NPC), and it is also one of the most serious complications of radiation therapy. In a broad sense, radiation brain injury is a series of pathophysiological changes that occur after nerve cells and intracranial blood vessels are damaged after radiation therapy, and there may be brain lesions visible in imaging. The most common manifestations are progressive intracranial pressure increase and brain herniation caused by extensive cerebral edema, and later in the disease, central nervous system (CNS) damage such as cognitive dysfunction, epilepsy, and severe dementia occurs. Once it occurs, it will be ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883A61K45/00A61P25/00
CPCC12Q1/6883A61K45/00A61P25/00C12Q2600/136C12Q2600/158C12Q2600/178
Inventor 崔理立周海红孙芙蓉区铭乾
Owner AFFILIATED HOSPITAL OF GUANGDONG MEDICAL UNIV
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