Use of trehalose in preparation of medicament for alleviating ischemia-reperfusion-induced acute kidney injury-related disorders

A technique for ischemia-reperfusion and acute kidney injury, applied in drug combinations, cardiovascular system diseases, pharmaceutical formulations, etc., can solve problems such as damage to kidney structure and function, and achieve the effect of improving kidney function

Inactive Publication Date: 2020-08-07
NANJING CHILDRENS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The invention provides the use of trehalose in the preparation of medicines for treating acute kidney injury, and solves the technical pro...

Method used

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  • Use of trehalose in preparation of medicament for alleviating ischemia-reperfusion-induced acute kidney injury-related disorders
  • Use of trehalose in preparation of medicament for alleviating ischemia-reperfusion-induced acute kidney injury-related disorders
  • Use of trehalose in preparation of medicament for alleviating ischemia-reperfusion-induced acute kidney injury-related disorders

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Experimental program
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Effect test

Embodiment 1

[0019] Embodiment 1 Materials and methods

[0020] 1) Materials and reagents

[0021] Trehalose was purchased from Sigma Company in the United States, NGAL antibody was purchased from Abcam Company, KIM-1, MPO, and 4-hydroxynonenal antibodies were purchased from R&D Systems Company, ATG5 was purchased from Nanjing Biotech Company, LC3B was purchased from Sigma-Aldrich Company, COX -2 was purchased from Cayman Company, and ATPB, IL-6, TNFα, SOD2, and β-actin antibodies were purchased from Proteintech Company. Fluorescent secondary antibodies were purchased from Invitrogen. CCK8 kit was purchased from KeyGen Biotech. Apoptosis detection kit was purchased from Vazyme Company. MDA and ROS detection kits were purchased from Beyotime Company. Mitochondrial membrane potential detection kit was purchased from Thermofisher.

[0022] 2) Cell culture and treatment

[0023] Mouse renal tubular epithelial cells (mPTCs) were cultured in DMEM / F12 medium containing 10% fetal bovine seru...

Embodiment 2

[0038] Example 2 Trehalose improves renal injury and renal function in an acute kidney injury model induced by ischemia-reperfusion

[0039] In order to evaluate the role of trehalose in the protection of renal ischemia-reperfusion injury, we detected the relevant biochemical indicators of the mouse kidney. After 24 hours of renal ischemia-reperfusion modeling, serum muscle and blood urea nitrogen indicators were significantly increased, while Renal tubular dilatation and necrosis and other renal pathological damage were also more serious, and after trehalose treatment, the corresponding renal damage and renal function indicators were significantly decreased ( figure 1 A, B, D). In addition, renal tubular damage score also suggested that trehalose treatment could improve renal pathological damage caused by cisplatin ( figure 1 C). Therefore, trehalose can not only improve renal function, but also reduce renal pathological damage. These results suggest that trehalose can pro...

Embodiment 3

[0041] Example 3 In the acute kidney injury model induced by ischemia-reperfusion, trehalose enhanced autophagy and relieved apoptosis and oxidative stress.

[0042] Apoptosis induced by renal ischemia-reperfusion injury was detected by TUNEL staining. Such as image 3 As shown in E, the number of TUNEL-positive cells in the renal tubules of ischemia-reperfused mice was significantly increased and significantly decreased after trehalose treatment. These findings suggest that Tre treatment attenuates apoptosis in a model of inner kidney ischemia-reperfusion injury.

[0043] Renal ischemia-reperfusion injury weakens the antioxidant capacity of the injured kidney and aggravates oxidative stress. The results of western blot analysis showed that trehalose treatment completely prevented ischemia-reperfusion-induced downregulation of mitochondrial respiratory chain-related proteins such as mitochondrial SOD (SOD2) and ATPB ( Figure 4 A-C). In addition, the detection results of M...

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Abstract

The invention provides application of trehalose in preparation of a medicine for relieving renal ischemia-reperfusion injury, and belongs to the field of biological medicines. The application proves that trehalose can alleviate ischemia-reperfusion induced acute kidney injury related diseases, including acute kidney injury renal function, oxidative stress, renal tubular cell apoptosis, renal inflammatory cell infiltration and the like, by enhancing autophagy, thereby providing a theoretical basis for widening the possible application range of trehalose. As trehalose has been approved to be a safe food component by American Food and Drug Administration at present and has been applied to food preservation and other work, it is found that effective clinical drugs are extremely likely to be provided for prevention and treatment of AKI.

Description

technical field [0001] The present invention relates to a new use of trehalose, in particular to the use of trehalose in the preparation of medicines for alleviating ischemia-reperfusion-induced acute kidney injury-related diseases. Background technique [0002] Acute kidney injury (acute kidney in jury, AKI) is a common clinical syndrome, mainly manifested as a rapid decline in renal function and accumulation of metabolic waste, an increase in serum creatinine (Scr) and a decrease in urine output Is the basis for the diagnosis of AKI. The incidence of AKI is high and is increasing year by year. A cross-sectional study in 2013 showed that the detection rate of AKI among hospitalized patients in my country was as high as 2%. It is predicted that 2.9 million AKI patients will be hospitalized and about 700,000 patients will die of AKI. At present, there is no specific drug for the treatment of AK1, and renal replacement therapy is required in severe cases. The risk of develop...

Claims

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Application Information

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IPC IPC(8): A61K31/734A61P13/12A61P9/10
CPCA61K31/734A61P9/10A61P13/12
Inventor 杨运文黄松明张爱华贾占军刘素雯周宁高慧萍王佩培
Owner NANJING CHILDRENS HOSPITAL
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