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Kupffer cell activity inhibitor and application of inhibitor in preparation of drug for treating acute liver failure

An activity inhibitor, a technology for acute liver failure, applied in the application field of Kuffer cell activity inhibitor, preparation of medicine for treating acute liver failure

Pending Publication Date: 2020-05-29
SHANGHAI SIXTH PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there is no report on whether the activity of Küffer cells is related to the IL-1 family, and there is an urgent need for a drug that can replace liver transplantation and can effectively treat acute liver failure

Method used

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  • Kupffer cell activity inhibitor and application of inhibitor in preparation of drug for treating acute liver failure
  • Kupffer cell activity inhibitor and application of inhibitor in preparation of drug for treating acute liver failure
  • Kupffer cell activity inhibitor and application of inhibitor in preparation of drug for treating acute liver failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] In this example, by constructing different treatment groups, the relationship between rhIL-1Ra and the survival rate of mice with acute liver failure and the effect of rhIL-1Ra on Kupffer cells were verified at the animal level and liver histological level. Include the following steps:

[0028] 1. Observation of mortality: All mice (n=39) received a single intraperitoneal injection of 750 mg / kg acetaminophen. One hour later, the rhIL-IRa group (n=10) was subcutaneously injected with 1 mg / kg rhIL-IRa every 12 hours until paracetamol injection for 24 hours. GdCl 3 Group (n=10) mice were subcutaneously injected with 30 mg / kg GdCl 24 hours before paracetamol injection 3 . Both the normal saline group (n=5) and the acetaminophen group (n=14) were treated with normal saline 1 hour after the injection of normal saline or acetaminophen as a control. The number of dead mice in each group after injection of acetaminophen was recorded every 2 h.

[0029] 2. Measurement of cytok...

Embodiment 2

[0045] In this example, the co-culture of Küffer cells and hepatocytes was used to explore the relationship between Küffer cells and hepatocytes cultured in the serum of mice with acute liver failure.

[0046] 1. Isolation of Küffer cells from hepatocytes: Küffer cells were isolated from wild-type male C57BL / 6 mice by collagenase digestion and differential centrifugation using a slightly modified percoll method as previously described (Abe et al. , 2004). Briefly, the liver is perfused via the portal vein with 100ml Ca 2+ and Mg 2+ Perfusate without HBSS at 37°C with a flow rate of 5ml / min. It was then perfused with complete HBSS containing 0.05% collagenase for 10 min at 37°C. Then remove the liver, mince it with HBSS / collagenase IV solution, stir continuously, 37°C, 20min. Liver slurry was filtered through a 100-mesh filter and washed with HBSS. The filtrate was centrifuged at 1000g for 5min, resuspended in PBS (pH7.4) to a final volume of 10ml, and centrifuged at 500g ...

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Abstract

The invention relates to the field of biomedicine, and provides a Kupffer cell activity inhibitor. The activity inhibitor is a recombinant human IL-1 receptor antagonist (rhIL-1Ra). Experiments find that the rhIL-1Ra significantly inhibits the activity of large Kupffer cells with high expression of IL-1RI, and inhibits the ultrastructure and phagocytic activity of Kupffer cells, thereby inhibitingthe activity of the Kupffer cells, significantly reducing hepatocyte apoptosis and promoting liver cell proliferation. According to the above conclusions, the recombinant human IL-1 receptor antagonist (rhIL-1Ra) reduces the hepatocyte apoptosis and promotes hepatocyte regeneration by inhibiting the activity of the Kupffer cells, and provides a strategy for preparing a drug for treating acute liver failure and liver injury.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a Kuffer cell activity inhibitor and its application in the preparation of medicines for treating acute liver failure. Background technique [0002] Acute liver failure is a serious disease with rapid onset and high mortality, which can be caused by hepatitis virus, drugs, surgery and other conditions (Bernal et al., 2015). Clinically, there is currently no drug that significantly improves the survival rate of patients with acute liver failure. The only effective method currently recognized for the treatment of acute liver failure is liver transplantation. However, due to the lack of donor liver sources and the high cost of treatment, this procedure is still not widely available (Lee et al., 2015, 2008). [0003] IL-1Ra is an important member of the IL-1 family. The main members of this family include two active ligands, leukin-1 (IL-1α) and interleukin-1β (IL-1β); an antagonist kno...

Claims

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Application Information

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IPC IPC(8): A61K38/20A61P1/16
CPCA61K38/2006A61P1/16
Inventor 胡建军
Owner SHANGHAI SIXTH PEOPLES HOSPITAL
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