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Application of cilomilast in preparation of drug for treating symptoms associated with acute kidney injury

A technology for acute kidney injury and related diseases, applied in the field of cilomilast, can solve problems such as AKI that has not yet been

Active Publication Date: 2019-06-21
NANJING CHILDRENS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as another PDE4 inhibitor, Cilomilast has not been reported to improve AKI caused by cisplatin

Method used

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  • Application of cilomilast in preparation of drug for treating symptoms associated with acute kidney injury
  • Application of cilomilast in preparation of drug for treating symptoms associated with acute kidney injury
  • Application of cilomilast in preparation of drug for treating symptoms associated with acute kidney injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Effect of Cilomilast on renal function in cisplatin-induced acute kidney injury.

[0036] Male C57BL / 6 mice weighing 18-22 g were taken and divided into 3 groups, namely the control group, the cisplatin model group and the Cilomilast treatment group (n=8).

[0037] Control group: intraperitoneal injection of equal volume medium once a day for 4 days in total;

[0038] Cisplatin model group: intraperitoneal injection, 20mg / kg, single administration;

[0039]Cilomilast treatment group: Cilomilast was administered for 1 day in advance (intraperitoneal injection, 30 mg / kg, Cilomilast, 200 μL / time), followed by a single administration of cisplatin (intraperitoneal injection, 20 mg / kg), Cilomilast was treated for another 3 days, and cisplatin was injected Blood was collected after 72 hours, and kidney tissue was retained.

[0040] The blood sample was centrifuged (20min, 3000r / min), and the creatinine assay kit (Creatinine Assay Kit (cat: K625-100, biomars)), urea...

Embodiment 2

[0042] Example 2 Effect of Cilomilast on the expression and secretion of cisplatin-induced renal inflammatory molecules.

[0043] The effects of Cilomilast on the expression and secretion of cisplatin-induced renal inflammatory molecules were studied by QPCR and ELISA.

[0044] Such as figure 2 As shown in A, the effect of Cilomilast on the expression and secretion of cisplatin-induced renal inflammatory molecules was studied by ELISA method. In the cisplatin-induced AKI model, the expression level of the inflammatory factor IL-6 in the cisplatin model group was significantly higher than that in the control group, p<0.01. The Cilomilast treatment group can significantly reduce the expression level of IL-6, p<0.01.

[0045] Such as figure 2 As shown in B, the QPCR method was used to study the effect of Cilomilast on the expression and secretion of cisplatin-induced renal inflammatory molecules. In the cisplatin-induced AKI model, the expression levels of inflammatory fact...

Embodiment 3

[0047] Example 3 Effect of Cilomilast on cisplatin-induced tubular cell apoptosis and kidney injury-related molecules.

[0048] QPCR and Western blot were used to detect the expression levels of kidney apoptosis and loss-related molecules to determine the improvement of Cilomilast on cisplatin-induced AKI. The results are as follows image 3 As shown, the expressions of apoptosis-related molecules Bax and Cleaved caspase 3 in the cisplatin model group were significantly increased; the expressions of damage-related molecules KIM-1 and NGAL were significantly increased. The Cilomilast treatment group can significantly reduce the expression levels of Bax, KIM-1, NGAL, and Cleaved caspase 3.

[0049] The results showed that Cilomilast could significantly reduce the expression levels of cisplatin-induced renal apoptosis and loss-related molecules.

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Abstract

The invention discloses a new indication of cilomilast. The invention provides cilomilast which can relieve cisplatin-induced acute renal injury related symptoms including acute renal tubular injury,renal function, apoptosis of renal tubular cells, expression and secretion of inflammatory factors and the like, and mainly relieves acute renal injury by inhibiting apoptosis of the renal tubular cells.

Description

technical field [0001] The present invention relates to a new application of Cilomilast, in particular to the application of Cilomilast in the preparation of medicines for cisplatin-induced acute kidney injury-related diseases. Background technique [0002] Acute kidney injury (acute kidney injury, AKI) refers to the sudden decline in renal function, which may or may not be accompanied by oliguria or anuria. The clinical syndrome is a sharp decline or loss of function in a short period of time, manifested as a sudden inability to maintain normal water and electrolyte balance, accumulation of metabolites in the body, and symptoms such as azotemia, water and electrolyte disorders, and metabolic acidosis. AKI is a clinical syndrome that can be secondary to a variety of diseases. It has the characteristics of acute onset, rapid progression, and high mortality. It is one of the important causes of chronic kidney disease. It is a group of serious clinical syndromes with a high mo...

Claims

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Application Information

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IPC IPC(8): A61K31/404A61P13/12
Inventor 张爱华于晓文贾占军许曼孟霞李树珍白咪袁慧黄松明张玥
Owner NANJING CHILDRENS HOSPITAL
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