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Application of secretory type Klotho in preparing medicine for treating chronic renal failure

A chronic kidney disease, secretory technology, used in gene therapy, drug combination, urinary system diseases, etc.

Inactive Publication Date: 2013-01-09
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still no effective drugs to delay the progression of CKD clinically.

Method used

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  • Application of secretory type Klotho in preparing medicine for treating chronic renal failure
  • Application of secretory type Klotho in preparing medicine for treating chronic renal failure
  • Application of secretory type Klotho in preparing medicine for treating chronic renal failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: Klotho protein binds to various Wnt proteins and inhibits Wnt / β-catenin signaling pathway activity

[0028] 1. Experimental materials:

[0029] Cells: mouse glomerular podocytes (a gift from Professor Peter Mundel, USA, see his paper Exp. Cell Res. 236: 248-258, 1997).

[0030] Differentiation medium: RPMI1640 medium containing 10% FBS, 100u / ml penicillin, and 100μg / ml streptomycin.

[0031] Proliferation culture medium: 50u / ml recombinant mouse IFN-γ was added to the above culture medium.

[0032] Proliferation culture method: cells were subcultured at 33 o C contains 5% CO 2 In the incubator, change the medium every other day.

[0033] Differentiation culture: To induce differentiation, podocytes are transferred to differentiation medium, 37 o C contains 5% CO 2 The incubator is used to differentiate podocytes for 10-14 days, and the medium is changed every other day.

[0034] 2. Experimental treatment:

[0035] Before the experiment, the podocyte...

Embodiment 2

[0039] Example 2: Inhibition of Klotho Protein on Kidney Fibrosis in UUO Mice

[0040] 1. Experimental animals: CD-1 mice, male, weighing 20-22g, SPF grade.

[0041] The animals were first weighed and numbered, and 21 healthy mice with a body weight of 20-22 g were selected and randomly divided into 3 groups, 7 in each group. Including sham operation group, model control group and medication group.

[0042] 2. Experimental grouping

[0043] 1) Sham-operated group: After the mice were anesthetized with 3% pentobarbital sodium at room temperature and 1ml / kg body weight, the incision was selected 1-2 cm below the left dorsal costal margin; after local disinfection, the skin, subcutaneous, and The muscle layer and peritoneum were sutured layer by layer after the left ureter was discovered. After local disinfection, check the marks and place them in corresponding mouse cages.

[0044] 2) Model control group: anesthetized and disinfected as above. The skin, subcutaneous layer...

Embodiment 3

[0056] Example 3: Inhibition of Klotho Protein on Kidney Fibrosis in ADR Mice

[0057] 1. Experimental animals: BABL / c mice, male, weighing 20-22g, SPF grade.

[0058] The animals were first weighed and numbered, and 21 healthy mice with a body weight of 20-22 g were selected and randomly divided into 3 groups, 7 in each group. Including normal saline group, model control group and medication group.

[0059] 2. Experimental groups

[0060] 1) Normal saline group: inject 2ml of normal saline into the tail vein at room temperature.

[0061] 2) Model control group: Doxorubicin was dissolved in normal saline, and 10 mg / kg body weight was injected into the tail vein once.

[0062] 3) Medication group: 1 week after doxorubicin injection, 2 ml of normal saline containing 1 mg / kg body weight of Klotho plasmid (same source as in Example 1) was injected into the tail vein, and then injected again every other week, for a total of 2 injections.

[0063] 3. Experimental procedure

...

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Abstract

The invention relates to application of anti-aging gene segments and protein products of the anti-aging gene segments in treating chronic renal failure, in particular to application of secretory type Klotho genes and proteins of the Klotho genes in preparing medicine for treating chronic renal failure. According to experiments, the secretory type Klotho has remarkable effect of restraining development of kidney tissue fibrosis and chronic renal failure and has no obvious side and toxic effects, so that the secretory type Klotho can be used for preparing medicines for treating chronic renal failure and particularly used for preparing medicines capable of effectively restraining and delaying development of chronic renal failure.

Description

technical field [0001] The present invention relates to the use of an anti-aging gene fragment and its protein product in the treatment of chronic kidney disease (CKD), in particular to the use of the secreted Klotho gene and its protein in the preparation of medicines for treating CKD. Background technique [0002] Chronic kidney disease (CKD) eventually progresses to end-stage renal failure (ESRD), and patients rely on "renal replacement therapy" for life to maintain their lives. In the past few decades, along with the aging of the human society, the prevalence of CKD has been increasing year by year (Nat Rev Nephrol, 2011, 7: 684-696). Some data indicate that CKD is becoming a "public health problem", which seriously endangers human health and consumes a lot of health resources. However, currently there are no drugs that can effectively delay the progression of CKD clinically. Aiming at the pathogenesis of CKD, finding drugs that can effectively inhibit or delay the pro...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K38/17A61P13/12
Inventor 刘友华周丽丽
Owner SOUTHERN MEDICAL UNIVERSITY
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