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Application of SB431542 in treating and inhibiting lupus nephritis

A technology of 1. SB431542, lupus nephritis, applied in the application field of treatment and inhibition of lupus nephritis, can solve the problems such as reports that SB431542 is not found in the treatment and inhibition of lupus nephritis, achieve inhibition of renal inflammation and antibody deposition, reduce the number, The effect of reducing antibody concentration

Inactive Publication Date: 2022-03-18
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In the prior art, there is no relevant report on the treatment and inhibition of lupus nephritis by SB431542

Method used

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  • Application of SB431542 in treating and inhibiting lupus nephritis
  • Application of SB431542 in treating and inhibiting lupus nephritis
  • Application of SB431542 in treating and inhibiting lupus nephritis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] In this example, SB431542 reduces CD20 expression and antibody levels in model mice. The specific experimental methods are as follows:

[0032] Twenty-seven female NZBWF1 mice were randomly divided into 3 groups with 9 mice in each group.

[0033] Group 1, denoted as normal group: normal feeding until 8 weeks old;

[0034] Group 2, denoted as the control group: intraperitoneal injection of 200 μL (normal saline: DMSO=500:1) and injection at the same time as the administration group.

[0035] Group 3, denoted as administration group: intraperitoneal injection of 200 μL (1.5 mg / ml) of SB431542.

[0036] The normal group was killed at the age of 8 weeks, and the peripheral blood, kidney tissue and spleen tissue were collected;

[0037] The control group and the treatment group were intraperitoneally injected three times a week, injected every other day, and stopped the drug for three weeks. This was one cycle, and the cycle was four cycles. The mice were killed at the ag...

Embodiment 2

[0041] This example studies that SB431542 reduces the activation of B cell-related pathways in model mice

[0042] The specific experimental method is:

[0043] After the mice in the control group and the administration group were treated in Example 1, fresh mouse kidneys were taken and frozen at -80°C. The kidneys of mice in each group were detected by transcriptome sequencing technology, and the differences between groups were compared by GO analysis and KEGG analysis.

[0044] Experimental results:

[0045] Transcriptome analysis showed that there were 586 differentially expressed genes (247 genes were down-regulated) between the control group and the treatment group, and the down-regulated genes were mainly enriched in the biological process of B cell activation, B cell proliferation, B cell differentiation and B cell receptor signal transduction (such as Figure 4 shown). KEGG analysis found that the hematopoietic cell linage pathway was significantly down-regulated (...

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Abstract

The invention belongs to the technical field of biology, and particularly relates to application of SB431542 in treatment and inhibition of lupus nephritis, the SB431542 is characterized in that 4-(imidazole-2-yl) benzamide is provided with additional 1, 3-benzodioxolane-5-yl and pyridine-2-yl substituent groups at the 4-site and the 5-site of an imidazole ring, and the SB431542 is provided with additional 1, 3-benzodioxolane-5-yl and pyridine-2-yl substituent groups at the 4-site and the 5-site of an imidazole ring; the SB431542 is used for relieving the autoantibody rise of the lupus nephritis and relieving the kidney inflammation of the lupus nephritis. The SB431542 is innovatively applied to treatment and inhibition of lupus nephritis, and in a mouse model of spontaneous lupus nephritis, it is found that the SB431542 has the effects of reducing the number of kidney and spleen B cells, reducing the concentration of peripheral blood antibodies of mice and inhibiting kidney inflammation and antibody deposition; the SB431542 maintains the immune homeostasis under the lupus nephritis condition by inhibiting the activation of B cells, and inhibits the generation of autoantibodies.

Description

technical field [0001] The invention belongs to the field of biotechnology, and specifically relates to the application of SB431542 in the treatment and inhibition of lupus nephritis. Background technique [0002] Lupus nephritis (LN) is one of the most serious organ manifestations of the autoimmune disease systemic lupus erythematosus (Systemic Lupus Erythematosus, SLE). In LN, immune complexes are deposited and inflammatory cells accumulate, leading to renal inflammation and injury. The pathogenesis of LN is the persistent production of multiple autoantibodies against self-antigens. B cells and plasma cells are the source of these autoantibodies. Studies have shown that lupus susceptible mice lacking B cells did not develop nephritis, but after injecting antibodies from lupus mice into normal mice, normal mice developed Glomerular immune complexes are deposited and manifest lupus nephritis. [0003] CD20 is a protein expressed only by B lymphocytes, exists on the surfac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4439A61P37/02A61P13/12
CPCA61K31/4439A61P37/02A61P13/12
Inventor 王晓松夏莹杨明月
Owner JILIN UNIV
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