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Application of hexarelin to preparing kidney ischemia reperfusion injury protecting drugs/drug combinations

A technology of ischemia-reperfusion and composition, which is applied in the field of biomedicine and can solve problems such as lack of strong evidence for drug effects

Inactive Publication Date: 2019-06-21
THE AFFILIATED HOSPITAL OF QINGDAO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current studies on its protective effect on peripheral organs are mainly focused on myocardium, brain, skeletal muscle, etc., and its role in ischemia-reperfusion acute kidney injury is rarely reported.
In addition, the mechanism of acute kidney injury is still inconclusive, so there is still a lack of strong evidence for its drug effects, and it is of great significance for clinical diagnosis and treatment to explore drugs related to acute kidney injury for the pathogenesis

Method used

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  • Application of hexarelin to preparing kidney ischemia reperfusion injury protecting drugs/drug combinations
  • Application of hexarelin to preparing kidney ischemia reperfusion injury protecting drugs/drug combinations
  • Application of hexarelin to preparing kidney ischemia reperfusion injury protecting drugs/drug combinations

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment 1 Hexarelin pretreatment

[0026] Select 30 healthy male SPF grade SD rats aged 8 weeks and weighing 250-300g to raise them in isolated cages with independent air supply, the temperature is controlled at 21°C ± 2°C, the relative humidity is controlled at 50% ± 15%, day and night The cycle is 12h, normal diet. They were randomly divided into 5 groups, namely normal group, sham operation group, acute kidney injury (AKI) group, acute kidney injury after hexarelin (HEX+AKI) group, acute kidney injury after normal saline (Saline+AKI) groups of 6 each. Rats in the drug treatment group and the normal saline control group were treated with drugs by intraperitoneal injection 7 days before modeling. According to the experimental grouping, Hexarelin was given to the Hex+AKI group and the Saline+AKI group respectively (the dose was 100 μg / kg .d) and an equal volume of normal saline, the determination of the dose of hexarelin refers to the previous experimental research...

Embodiment 2

[0027] Example 2 Establishment of a rat kidney ischemia-reperfusion injury model

[0028] Rats were fasted for 12 hours before operation, free to drink water, weighed before operation, anesthetized by intraperitoneal injection of pentobarbital sodium (30mg / kg), opened along the middle of the abdomen, separated the layers of the abdominal cavity layer by layer, and carefully separated the left renal pedicle. And clipped with a micro-arterial clip, observed that the color of the kidney turned white instantly, the same operation was performed on the opposite side, and the vascular clip was released after 50 minutes. If the kidney changed from purple-black to red, the ischemia-reperfusion was successful, and the abdominal cavity was closed layer by layer. Attention should be paid to keeping warm and replenishing fluid, and returning to normal diet after the rats wake up. After 24 hours, the rat kidney tissue and fresh blood were collected for the next experiment. In the sham oper...

Embodiment 3

[0029] Example 3 Renal function test

[0030] 3.1 Detection of serum creatinine and blood urea nitrogen in model rats

[0031] Blood was collected from the inferior vena cava of rats and collected in serum tubes, left at room temperature for 1 hour, centrifuged in a high-speed centrifuge at 3,000 rpm for 15 minutes, and 200ul of upper serum was collected, and blood creatinine and blood urea nitrogen were detected by the picric acid method in an automatic biochemical analyzer.

[0032] 3.2 Detection of KIM-1 mRNA in model rats

[0033] 3.2.1 mRNA extraction

[0034] After the rat kidney ischemia-reperfusion injury model is successfully established, 10 mg of left kidney tissue is collected from each rat, and the total RNA of the tissue is extracted by the Trizol method, that is, 1 ml Trizol / sample is added when collecting the sample, and 200 μl chloroform is added to each sample after thorough grinding / ml Trizol, mix by hand, let stand on ice for 3min, then centrifuge at 1200...

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Abstract

The invention discloses application of hexarelin to preparing kidney ischemia reperfusion injury protecting drugs / drug combinations and belongs to the field of biological medicines. According to the application, the hexarelin is proved to possibly have protecting effects on rate ischemia reperfusion induced acute kidney injury; data prove that expression of SFN (stratifin) gene in a kidney ischemia reperfusion model is significantly increased, and with intervention of the hexarelin, is more significantly increased, while expression of apoptosis promoting genes of Bax, Bad and caspase3 are down-regulated, so that the hexarelin can protect kidney ischemia reperfusion injury by inhibiting apoptosis, and further by means of the molecular docking technology, possibility of interaction between hexarelin molecules and a 14-3-3 sigma protecting structure coded by the SFN gene can be testified, and a theoretical foundation for enlarging the possible application range of the hexarelin can be provided. The application of the hexarelin to preparing the kidney ischemia reperfusion injury protecting drugs / drug combinations can be applied to theoretical research and clinical application of kidneyischemia reperfusion injury and provide the theoretical foundation for enlarging the possible application range of the hexarelin.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of hexarelin in the preparation of a drug / medicine composition for protecting the kidney from ischemia-reperfusion injury. Background technique [0002] Acute Kidney Injury (AKI) refers to a series of clinical syndromes caused by a sudden (within 1-7d) and continuous (>24h) decline in glomerular filtration function due to various reasons, and it is common in renal artery embolism , kidney transplantation, severe renal vascular disease, shock, acute heart failure, etc. Studies have shown that renal proximal tubular epithelial cells are the most seriously affected part of renal ischemia-reperfusion injury, mainly manifested as renal tubular atrophy and disappearance, proximal tubular epithelial cells apoptosis, necrosis, shedding, and capillary around renal tubules reduce. Since there is still a lack of effective diagnostic and therapeutic means to block ...

Claims

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Application Information

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IPC IPC(8): A61K38/25A61P13/12
Inventor 徐岩管陈杨成宇
Owner THE AFFILIATED HOSPITAL OF QINGDAO UNIV
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