Polypeptide and its application in the treatment of acute kidney injury

A Kidney Injury, Acute Technique, Applied in Biopharmaceuticals

Active Publication Date: 2020-05-19
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current medical technology does not have a more effective means of treatment. Renal replacement therapy is often used to prolong the survival of patients with kidney disease. Therefore, it is imminent to find drugs to relieve renal ischemia-reperfusion injury.

Method used

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  • Polypeptide and its application in the treatment of acute kidney injury
  • Polypeptide and its application in the treatment of acute kidney injury
  • Polypeptide and its application in the treatment of acute kidney injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] 11 peptide and 32 peptide can inhibit the inflammation, DNA damage and apoptosis induced by hypoxia-reoxygenation injury in rat renal tubular cells (NRK-52E).

[0052] Specific operation: NRK-52E cells were treated and divided into normal group (CT group), hypoxia-reoxygenation group (H / R group), hypoxia-reoxygenation group given 32 peptide (E32 group), hypoxia-reoxygenation group 22 peptides (E22 group) and 11 peptides (E11 group) were given to the hypoxia-reoxygenation group. The cells in each group were collected, and after RNA was extracted, the relative mRNA levels of Kim1, Ilb, Icam1 and Tnfa in each group were checked by real-time quantitative PCR instrument ( figure 2 A). MTT experiments were performed on cells treated with different groups ( figure 2 B), detecting the viability of cells. NRK-52E cells were collected, ultrasonically lysed, and DNA damage-related proteins (p-ATR, p-Chk1 and p-H2A.X) and apoptosis-related proteins (caspase3 and c-caspase3) we...

Embodiment 2

[0056] 32-peptide and 11-peptide can inhibit DNA damage induced by doxorubicin (ADR) in renal tubular cells (NRK-52E)

[0057] Specific operation: NRK-52E cells were treated and divided into normal group (PBS group), ADR treatment (ADR group), 32 peptides after ADR treatment (E32 group), 22 peptides after ADR treatment (E22 group) and After ADR treatment, 11 peptides were given (E11 group). The cells with different treatments in each group were subjected to MTT experiment to detect the survival rate of the cells ( Figure 4 A). NRK-52E cells were collected, ultrasonically lysed, and DNA damage-related proteins (p-ATR, p-Chk1 and p-H2A.X) and apoptosis-related proteins (caspase3 and c-caspase3, PARP-1 and c -PARP-1) (eg Figure 4 B and C).

[0058] Experimental results such as Figure 4 As shown, after ADR treatment, the protein levels of p-ATR and p-Chk1 were significantly down-regulated after administration of 32 peptides and 11 peptides to NRK-52E cells. After administ...

Embodiment 3

[0060] The polypeptide of the present invention can inhibit the change of kidney shape, inflammation and fibrosis caused by renal ischemia-reperfusion (I / R for short) of C57BL / 6 mice.

[0061] Specific operation: Before the formal experiment, we conducted a series of polypeptide injection dose pre-experiments of the present invention. After the injection of the series of polypeptides, the physiological indicators of the mice were normal in all aspects, and the series of polypeptides were considered to be safe.

[0062] The mice weighing about 25 g were divided into three groups: control mouse group (CT group), renal ischemia-reperfusion mouse group (I / R group), renal ischemia-reperfusion mouse group given 32 peptide (E32 group) and renal ischemia-reperfusion mouse group were given 11 peptide group (E11 group). The renal ischemia-reperfusion mouse group underwent I / R surgery for 45 minutes. The control mouse group (CT group) and the renal ischemia-reperfusion mouse group (I / R ...

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Abstract

The invention discloses a peptide 11 with carboxyl at a C terminal, as well as a peptide 32 and a peptide 22 comprising an amino acid sequence of the peptide 11. The peptide 32 and the peptide 11 can achieve the effects of obviously inhibiting DNA damage response, apoptosis and inflammation of renal tubular cells subjected to treatment of adriacin doxorubicin (ADR) and hypoxia / reperfusion (H / R), wherein the peptide 11 has the optimal effect. In a C57 mouse model, the peptide 32 and the peptide 11 can achieve an effect of obviously relieving ischemia reperfusion injury (I / R injury for short) of the mouse kidney, and the peptide 22 can also relieve the injury to a certain degree. The peptide 11, the peptide 32 and the peptide 22 disclosed by the invention can be used for preparing treatment medicines for treating acute kidney injury.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals, and more specifically relates to a polypeptide and its application in treating acute kidney injury. Background technique [0002] Acute kidney injury is a disease with a high mortality rate in the world. The ischemia or toxic injury of renal tubular cells results in a sharp decline in renal function. Acute kidney injury is one of the important causes of end-stage renal disease. Acute kidney injury occurs in 133 million people each year and is responsible for approximately 170 deaths each year. [0003] Renal ischemia-reperfusion injury is the leading cause of acute kidney injury and causes a high mortality rate worldwide. The pathological process of renal ischemia-reperfusion includes the occurrence of inflammation and apoptosis. Effective inhibition of pro-inflammatory cytokines and apoptosis protects against acute renal ischemia-reperfusion injury. The current medical technology does not h...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06C07K14/00A61K38/08A61K38/16A61P13/12A61P3/10
CPCA61K38/00C07K7/06C07K14/00
Inventor 黄昆陈红程呈黄依雪王超
Owner HUAZHONG UNIV OF SCI & TECH
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