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MiRNA for preventing and/or treating acute pancreatitis, and pharmaceutical application of MiRNA

A technology for acute pancreatitis, inflammatory response, applied in the field of biomedicine

Active Publication Date: 2021-09-14
YANGZHOU FIRST PEOPLES HOSPITAL +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there is no report on MicroRNA targeting acute pancreatitis

Method used

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  • MiRNA for preventing and/or treating acute pancreatitis, and pharmaceutical application of MiRNA
  • MiRNA for preventing and/or treating acute pancreatitis, and pharmaceutical application of MiRNA
  • MiRNA for preventing and/or treating acute pancreatitis, and pharmaceutical application of MiRNA

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: Expression of miR-133a in cerulein-induced acute pancreatitis in mice

[0041] A mouse model of mild acute pancreatitis induced by cerulein

[0042] Experimental animals: 6-8 week male C57BL / 6J mice (body weight 20-25g).

[0043] The experimental animals were divided into normal control group and different time (3h, 6h, 12h) model groups. The mice in the model group were intraperitoneally injected with cerulein (100ug / kg, 1 hour apart, 7 consecutive injections) to establish an acute pancreatitis model. The mice in the control group were given intraperitoneal injection of strict PBS control. The mouse serum was collected for detection of serum enzyme levels and inflammatory factor levels. Subsequently, the mice underwent in vivo heart perfusion to remove blood in the circulation, quickly extracted pancreatic tissue for fixed dehydration, made HE-stained paraffin sections and fluorescent in situ hybridization staining, the results can be found in figure 1 ,...

Embodiment 2

[0044] Example 2: Application of miR-133a agonist in prevention / treatment of acute pancreatitis

[0045] 1. The mouse model of acute pancreatitis induced by cerulein

[0046] According to the actual operation in Example 1 and the induction of the model, the 12h cerulein induction model was selected as a follow-up study. The modeling method is the same as in Example 1.

[0047] 2. Intraperitoneal injection of miR-133a agonist

[0048] The mice in the model group were randomly divided into Control group, AP (acute pancreatitis) group, and miR-133a agonist (1ug / mouse) prophylactic treatment group, with 7 mice in each group, and agomir-miR was injected continuously intraperitoneally five days before cerulean modeling -133a (dissolved in PBS solution) up-regulated the expression of miR-133a. Mice in the control group were given strict control agomir. On the sixth day, all mice were intraperitoneally injected with cerulein to establish a mouse AP model, and 12 hours after the fi...

Embodiment 3

[0050] Example 3: expression of miR-133a in cholecystokinin (CCK)-induced AP acinar cell injury

[0051] Primary acinar cells: extract pancreatic acinar cells from 6-8 week old C57 / BL6 male mice, inoculate in a six-well plate, use 1M Hepes medium (containing 10% FBS), 37 degrees Celsius, 5% CO2 incubator Stable cultivation. The in vitro cell injury (0h, 1h, 3h, 6h) model was established by giving CCK.

[0052] Mouse pancreatic acinar cell carcinoma line (266-6 cells): Inoculate 266-6 cells (purchased from ATCC library) on 25cm 2 In the cell culture flask, use DMEM medium (containing 10% FBS, 100U / ML penicillin and 100ug / ml streptomycin), 37 degrees Celsius, 5% CO 2 Stable culture and passage in the incubator. Cells in good condition during the logarithmic growth period were inoculated into six-well plates, replaced with new DMEM medium, and given CCK to establish an in vitro cell injury (0h, 3h, 6h, 9h) model.

[0053] The level of miR-133a mRNA in acinar cells was observe...

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Abstract

The invention discloses miRNA for preventing and / or treating acute pancreatitis, and pharmaceutical application of the MiRNA, and belongs to the technical field of biological medicines. The invention provides application of a miR-133a agonist in preparation of a medicine for inhibiting the acute pancreatitis, and makes clear that the miR-133a agonist is miRNA of which the nucleotide sequence is shown as SEQ ID NO: 1. Through simulation of a clinically related acute pancreatitis model, the miR-133a agonist is proved to be capable of remarkably improving occurrence and development of the above AP model, and can be used for clinically preventing / treating the AP. Meanwhile, the invention also proves through an in-vitro acinus cell AP model that the protection effect of the miR-133a agonist for the acute pancreatitis is that macrophages carry out targeted "removal" on the damaged acinus cells to realize the functions of alleviating the AP inflammatory response and reducing AP severity. The invention provides a new drug source for prevention, diagnosis, detection, protection, treatment and research of pancreatitis diseases, can be easily popularized and applied clinically, and can generate a huge clinical application prospect and social benefit in a relatively short time.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a miRNA for preventing and / or treating acute pancreatitis and its pharmaceutical application. Background technique [0002] Acute pancreatitis (AP) is a kind of digestive tract inflammatory disease with rapid onset, rapid progression and high mortality rate. The pathogenesis is still unclear. Scholars at home and abroad believe that the clinical etiology of AP is relatively complex. Excessive drinking, gallstones, hyperlipidemia, and duodenal reflux may first affect acinar cells, cause excessive activation of zymogens, and induce the development of AP. Most clinical patients only show local pancreas injury and inflammatory response, which can be recovered after conservative medical treatment, and about 20%-30% may progress to severe acute pancreatitis (Sever acute pancreatitis, SAP) due to poor control or recurrent attacks, and die The rate is extremely high, which has attract...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113A61K48/00A61K31/7105A61P1/18A61P29/00
CPCC12N15/113A61K31/7105A61P1/18A61P29/00C12N2310/141Y02A50/30
Inventor 朱擎天路国涛袁晨晨张俊贤肖炜明龚卫娟胡良皞
Owner YANGZHOU FIRST PEOPLES HOSPITAL
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