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Application of miR-214 antagonist in preparing drug for relieving kidney tubule lesion-related diseases caused by proteinuria

A related disease, 1. mir-214 technology, applied in drug combinations, urinary system diseases, pharmaceutical formulations, etc., can solve problems such as no miR-214 antagonists yet

Inactive Publication Date: 2018-01-26
NANJING CHILDRENS HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is no report of miR-214 antagonists against albumin-induced renal tubular injury

Method used

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  • Application of miR-214 antagonist in preparing drug for relieving kidney tubule lesion-related diseases caused by proteinuria
  • Application of miR-214 antagonist in preparing drug for relieving kidney tubule lesion-related diseases caused by proteinuria
  • Application of miR-214 antagonist in preparing drug for relieving kidney tubule lesion-related diseases caused by proteinuria

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 Effect of miR-214 antagonists on albumin-induced renal function.

[0045] Male C57BL / 6 mice weighing 18-22 g were divided into 4 groups, namely, the blank control group (vehicle+anti-control (anti-control is an oligonucleotide sequence without any function: 5'-3'ACGTCTATACGCCCA ), miR-214 antagonist group (vehicle+anti-miR-214), albumin model group (Albumin+anti-control) and miR-214 antagonist+albumin group (anti-miR-214+ albumin).

[0046] Albumin model group: intraperitoneal injection, gradually increasing body weight from 2 mg / g to 10 mg / g body weight on the fifth day, and maintaining intraperitoneal injection of 10 mg / g body weight for the next 6 days, a total of 11 days, the mice were killed on the 12th day, and the kidneys were collected organize.

[0047] miR-214 antagonist treatment group (i.e. miR-214 antagonist + albumin group): the miR-214 antagonist was formulated with RNAase-removed physiological saline to a concentration of 1 μg / μL, and administ...

Embodiment 2

[0051] Example 2 Effects of miR-214 antagonists on albumin-induced tubular cell apoptosis.

[0052] TUNEL (TdT-mediated dUTPNick-End Labeling) positive tubular cells in albumin-induced renal injury were detected by tissue immunohistochemistry.

[0053] Such as figure 2 As shown, in the albumin-induced kidney injury model, the blank control group (vehicle+anti-control), the miR-214 antagonist group (vehicle+anti-miR-214) had no obvious TUNEL positive cells under the microscope, and the albumin model group (Albumin+anti-control) had 21.4 ± 3.2 positive cells in each high-power field, and miR-214 antagonist treatment group (anti-miR-214+albumin) had 3.5±0.82 positive cells in each high-power field (n =6).

[0054] The results showed that administration of miR-214 antagonist alone had no effect on tubular cells. Albumin can induce a large amount of apoptosis of tubular cells, compared with the blank control group, p<0.05. And miR-214 antagonist can significantly reduce apopto...

Embodiment 3

[0055] Example 3 Effects of miR-214 antagonists on albumin-induced renal inflammation.

[0056] The expressions of renal inflammatory factors IL-1β, TNF-α and MCP-1 were detected by PCR, and the secretion of IL-1β in serum was detected by Western detection of MCP-1 and ELISA.

[0057] Compared with the blank control group, administration of miR-214 antagonist alone did not increase the expression of inflammatory factors, and the expression of inflammatory factors in the albumin model group increased significantly, p<0.05. And miR-214 antagonist can significantly reduce the expression of inflammatory factors, compared with albumin group, p<0.05.

[0058] The results showed that albumin could induce the increased expression of renal inflammatory factors, while miR-214 antagonist could inhibit the expression of inflammatory factors.

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Abstract

The invention discloses an application of a miR-214 antagonist in preparing a drug for relieving renal injury caused by proteinuria, especially the application in preparing the drug for relieving thekidney tubule lesion-related diseases, kidney inflammation and renal mitochondrial dysfunction caused by proteinuria.

Description

technical field [0001] The present invention relates to a new application of miR-214 antagonist, in particular to the application of miR-214 antagonist in the preparation of medicine for alleviating proteinuria-induced kidney damage. Background technique [0002] Proteinuria is a common feature of many kidney diseases. At present, it is believed that proteinuria first leads to tubulointerstitial damage, which in turn damages glomerular function and promotes the progression of kidney disease. More and more studies have shown that 24-hour urinary protein excretion is significantly correlated with the progression and prognosis of kidney disease. In different kidney diseases, controlling dietary protein intake or using drugs (ACEI, etc.) to reduce proteinuria can delay the deterioration of renal function; while excessive infusion of exogenous protein can aggravate proteinuria and aggravate renal function damage . Numerous clinical observations and experimental studies have sho...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K31/7088A61P13/12
Inventor 白咪张爱华
Owner NANJING CHILDRENS HOSPITAL
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