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Application of miR-665-3p inhibitor to preparation of medicine for preventing and treating ischemia-reperfusion injuries

A technology of ischemia-reperfusion and inhibitors, applied in drug combinations, pharmaceutical formulations, cardiovascular system diseases, etc.

Inactive Publication Date: 2017-05-24
THE SECOND HOSPITAL OF DALIAN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although recent studies have shown that miRNAs play a fine-tuning role in many different stages of autophagy, so far there is no research on the application of miR-665-3p inhibitors in the preparation of drugs for the prevention or treatment of ischemia-reperfusion injury. Related reports

Method used

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  • Application of miR-665-3p inhibitor to preparation of medicine for preventing and treating ischemia-reperfusion injuries
  • Application of miR-665-3p inhibitor to preparation of medicine for preventing and treating ischemia-reperfusion injuries
  • Application of miR-665-3p inhibitor to preparation of medicine for preventing and treating ischemia-reperfusion injuries

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0030] Experimental example 1. LNA-miR-665-3p can effectively treat small intestinal injury caused by ischemia-reperfusion

[0031] Divide 24 healthy C57BL / 6J mice into 4 groups:

[0032] A. Normal control group: sham operation group;

[0033] B. Normal administration group: sham operation + LNA-miR-665-3p (2 mg / kg);

[0034] C. Model group: small intestine ischemia-reperfusion group (II / R group);

[0035] D. Model administration group: II / R+LNA-miR-665-3p (2 mg / kg).

[0036] In this experiment, the Megision method was used to construct the small intestine I / R animal model. The brief steps are as follows: the mice were anesthetized routinely. The superior mesenteric artery (SMA) was gently separated, and the root of the SMA was clipped with a miniature non-invasive vascular clip. At this time, it was observed that the pulse at the distal end of the SMA disappeared, and the wall of the small intestine quickly changed from pink to pale, confirming the successful establishmen...

experiment example 2

[0047] Experimental example 2. LNA-miR-665-3p significantly improves the survival rate of mice with II / R injury

[0048] Divide 30 healthy C57BL / 6J mice into 2 groups:

[0049] A. miRNA control group: II / R+LNA-NC (2 mg / kg);

[0050] B. LNA-miR-665-3p administration group: II / R+LNA-miR-665-3p (2 mg / kg);

[0051] The model construction and drug administration methods were as described in Example 1, and the results after 24 h of reperfusion were shown in Figure 5 , * vs. miRNA control group p <0.01, n=15. The experimental results showed that the 24-hour survival rate of animals in the miR-665-3p administration group was significantly higher than that in the miRNA control group.

experiment example 3

[0052] Experimental example 3. Antagomir-miR-665-3p significantly reduces cell damage induced by hypoxia-reoxygenation

[0053] Hypoxia / Reoxygenation (H / R) is a commonly used cell injury model in vitro, which is used to simulate I / R injury in vivo. Caco-2 cells were used to construct H / R injury models, which were divided into 4 groups:

[0054] A. Normal control group: Control+Antagomir-NC (30nM);

[0055] B. Model control group: H / R+Antagomir-NC (30nM);

[0056] C. Normal administration group: Control+Antagomir-665-3p (30nM);

[0057] D. Model administration group: H / R+Antagomir-665-3p (30nM).

[0058] 3.1 Antagomir-miR-665-3p significantly increased the survival rate of Caco-2 cells after H / R injury

[0059] In this experiment, the model was constructed by hypoxia for 12 hours and reoxygenation for 6 hours. After the model was successfully constructed, the cell survival rate of each group was detected by the CCK-8 method. The results are shown in Figure 6 , ** vs. Con...

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Abstract

The invention discloses application of a miR-665-3p inhibitor to preparation of a medicine for preventing and treating ischemia-reperfusion injuries. The application proves that the miR-665-3p inhibitor can be used for remarkably improving the tolerance of intestinal cells on the ischemia-reperfusion injuries and alleviating the severity degree of the intestinal ischemia-reperfusion injuries; the miR-665-3p inhibitor is used for effectively alleviating phenomena of scaling and lodging of intestinal villi of mice, expansion and exposure of blood capillaries and the like; the miR-665-3p inhibitor can be used for remarkably inhibiting excessive releasing of intestinal injury marker intestinal fatty acid binding protein (I-FABP) and inflammatory cell factors including TNF-alpha and IL-6; and meanwhile, when the miR-665-3p inhibitor is used, the survival rate of mice subjected to mouse II / R injuries for 24h is remarkably higher than that of a control group.

Description

technical field [0001] The invention relates to a new application of miR-665-3p inhibitor, especially the application of miR-665-3p inhibitor in the preparation of drugs for preventing and treating ischemia-reperfusion injury. Background technique [0002] Ischemia-reperfusion injury refers to pathological changes in cells caused by tissue ischemia and hypoxia for a certain period of time. After the blood supply is restored, the damaged tissue not only fails to recover its function, but further aggravates the pathological phenomenon. Numerous literatures indicate that ischemia-reperfusion injury may be related to the following factors: 1. Generation of oxygen free radicals; 2. Calcium overload; 3. Activation of neutrophils (PMN); 4. Excessive apoptosis; 5. Release of numerous cytokines and inflammatory mediators. In short, ischemia-reperfusion injury is the result of the interaction and comprehensive effect of various mechanisms. [0003] Autophagy is a lysosome-dependent ...

Claims

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Application Information

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IPC IPC(8): A61K31/7088A61P9/10
CPCA61K31/7088
Inventor 田晓峰李振鲁姚继红王广智封东成李扬
Owner THE SECOND HOSPITAL OF DALIAN MEDICAL UNIV
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