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Purposes of PMNs in preparation of medicine for treating and/or preventing autoimmune hepatitis

A neutrophil and autoimmune technology, applied in the field of medicine, can solve the problems of no neutrophils for the treatment of autoimmune hepatitis, no reports of neutrophils phagocytosing and apoptotic liver cells, etc. Benefits and economic benefits, pain relief effects

Active Publication Date: 2019-12-24
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] So far, there has been no report on the phagocytosis of apoptotic hepatocytes by neutrophils, let alone the use of neutrophils in the treatment of autoimmune hepatitis

Method used

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  • Purposes of PMNs in preparation of medicine for treating and/or preventing autoimmune hepatitis
  • Purposes of PMNs in preparation of medicine for treating and/or preventing autoimmune hepatitis
  • Purposes of PMNs in preparation of medicine for treating and/or preventing autoimmune hepatitis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 Neutrophils in human normal liver tissue phagocytize apoptotic hepatocytes, and neutrophils in patients with autoimmune hepatitis have defects in neutrophils

[0063] This example is mainly to compare normal human liver tissue samples and autoimmune hepatitis liver tissue samples, to study neutrophil scavenging effect on apoptotic liver cells and neutrophil phagocytosis defects in autoimmune liver cases, so as to reveal neutrophils A new function of granulocytes - removal of apoptotic cells.

[0064] 1. Experimental design

[0065] (1) Phagocytosis of apoptotic hepatocytes by neutrophils in normal human liver tissue

[0066] In this part of the experiment, the adjacent non-cancerous liver normal tissues were obtained from liver cancer patients. 1) Slice the tissue, stain with HE and TUNEL, observe the degree of nuclear pyknosis and count the number of neutrophils and apoptotic cells ; 2) Tissue sectioning of non-cancerous liver normal tissues, using TUNEL to...

Embodiment 2

[0096] Example 2 The scavenging effect of neutrophils on apoptotic hepatocytes in vitro

[0097] This part of the research mainly observes the phagocytosis of neutrophils on apoptotic hepatocytes and other cells in vitro, and the leakage of the contents of neutrophils during the phagocytosis process, so as to reveal the effect of neutrophils on apoptotic liver cells. The scavenging effect is achieved by drilling and phagocytosis.

[0098] 1. Experimental design

[0099] (1) Study the phagocytosis of neutrophils on apoptotic hepatocytes at the cellular level

[0100] The human PMN cell line HL-60, human liver cells L02, HL-60-GFP, and L02-Tomato established by the research group will be used in this part of the in vitro experimental research. Human liver cell L02 was induced by puromycin or TGF-β, 1) L02 was stained with red membrane dye (PKH-26), and differentiated HL60 was stained with green membrane dye (PKH-67). The differentiated HL60 was added to normal L02 and apoptot...

Embodiment 3

[0137] Example 3 Establishing an Autoimmune Hepatitis Mouse Model to Study the Phagocytosis of Neutrophils in Vivo

[0138] Defective neutrophil-deficient mediated clearance of apoptotic cells has been previously observed in human autoimmune liver disease (AIL), which induces an inflammatory response and leads to the production of self-antigens. This part studies 1) the phagocytosis of neutrophils in a mouse model of autoimmune hepatitis; 2) the extent of defects in apoptotic cell clearance after knockout of neutrophils in mice; 3) the restoration of neutrophils The clearance of apoptotic cells and the relief of AIL disease symptoms. Elucidate that neutrophils clear apoptotic cells and maintain tissue homeostasis.

[0139] 1. Experimental design

[0140] (1) Single / two-photon in vivo microscopic imaging system to study the phagocytosis of neutrophils on apoptotic hepatocytes under physiological conditions

[0141] In this part of the study, the existing C57BL / 6 mice in the ...

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Abstract

The invention relates purposes of PMNs in preparation of medicine for treating and / or preventing autoimmune hepatitis, and belongs to the field of medicine. On one hand, the invention provides the purpose of the PMNs in the preparation of the medicine for treating and / or preventing autoimmune hepatitis and the purpose in preparation of medicine for clearing apoptotic hepatocytes. On the other hand, the invention also provides an auxiliary diagnostic kit for the autoimmune hepatitis. The application of the invention can provide a novel option for the clinic diagnosis and treatment of the autoimmune hepatitis; the pain caused by the autoimmune hepatitis on a patient is favorably relieved; and important social benefits and economic benefits are realized.

Description

technical field [0001] The invention relates to the use of neutrophils in the preparation of medicines for treating and / or preventing autoimmune hepatitis, and belongs to the field of medicine. Background technique [0002] Apoptosis is a programmed cell death process that clears aged or damaged cells to maintain internal tissue homeostasis. In the adult human body, hundreds of billions of cells die every day. These cells must be processed quickly and efficiently without leakage of cytoplasm or causing an inflammatory response. Defective clearance of apoptotic cells is often associated with a variety of inflammatory responses and autoimmune diseases. It is generally accepted that apoptotic cells are cleared by professional phagocytes (eg, macrophages, mature dendritic cells) or adjacent non-professional phagocytes (eg, epithelial cells, endothelial cells, and fibroblasts). Although the morphology of apoptotic cells is easily distinguished in histological sections, apoptot...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/15A61K45/00A61P1/16A61P37/02G01N33/50G01N33/576G01N33/68G01N33/533
CPCA61K35/15A61K45/00A61P1/16A61P37/02G01N33/5067G01N33/533G01N33/576G01N33/6854G01N33/6869G01N2333/5421G01N2333/545
Inventor 徐劲松曹路扬赛音贺西格
Owner SICHUAN UNIV
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