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Application of pro-angiogenic factor PDGFC as marker for diagnosis and treatment of hepatopulmonary syndrome

A technology for promoting angiogenesis and pulmonary syndrome, applied in the field of biomedicine, can solve problems such as poor therapeutic effect, no definite effect, limited oxygen exchange and diffusion function, and achieve the effect of promoting proliferation

Active Publication Date: 2020-02-21
THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Pathological angiogenesis is one of the core changes in the process of HPS, that is, extensive dilation and neovascularization at the capillary level lead to mismatch between ventilation and perfusion, restricted oxygen exchange diffusion function, and arteriovenous shunt. Smooth muscle cells respond less to endogenous and exogenous vasoconstrictor factors, resulting in poor efficacy of traditional treatment; studies have shown that indomethacin, tamoxifen, somatostatin and sympathomimetic drugs, β-blockers, etc. show exact role

Method used

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  • Application of pro-angiogenic factor PDGFC as marker for diagnosis and treatment of hepatopulmonary syndrome
  • Application of pro-angiogenic factor PDGFC as marker for diagnosis and treatment of hepatopulmonary syndrome
  • Application of pro-angiogenic factor PDGFC as marker for diagnosis and treatment of hepatopulmonary syndrome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1, screening of pro-angiogenic factors

[0020] The proteomics method was used to screen the molecules with high abundance in the blood of HPS model rats that may be related to angiogenesis, and the specific methods were as follows:

[0021] (1) Constructing a rat model of hepatopulmonary syndrome by ligation of the common bile duct

[0022] The HPS rat model was established by common bile duct ligation (CBDL), 30 rats in the sham group and 30 in the operation group. SD male adult rats, weighing 200-220 g, were used to establish an animal model of HPS by common bile duct ligation (common bile duct ligation, CBDL). Rats in the control group were only subjected to laparotomy without ligation of the common bile duct. Blood gas analysis was used to judge the expansion of pulmonary microvessels: after weighing the rats, they were anesthetized with 5% chloral hydrate at 7 mL / g; the abdominal cavity was quickly opened to expose the abdominal aorta, and blood was draw...

Embodiment 2

[0027] Example 2, verifying the angiogenesis-promoting function of PDGFC

[0028] Using the constructed PDGFC knockdown and overexpression lentivirus (Follenzi A, Ailles LE, Bakovic S, Geuna M, Naldini L: Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1pol sequences. Nature genetics 2000, 25(2):217-222.) deal with pulmonary microvascular endothelial cells, and measure the pro-angiogenic function of microvascular endothelial cells through the proliferation, migration and tube-forming ability of microvascular endothelial cells.

[0029] The results of cell proliferation experiments ( figure 2 , A) showed that the number of Ki67-positive cells in the PDGFC overexpression group was significantly higher than that in the control group, and the number of Ki67-positive cells in the PDGFC knockdown group was significantly lower than that in the control group, which indicated that PDGFC overexpression can promote the angiogenesis ability of p...

Embodiment 3

[0032] Embodiment 3, preparation polyclonal antibody, evaluates the influence on the state of an illness of HPS rat

[0033] First, a polyclonal antibody to PDGFC was prepared. The method of preparing polyclonal antibodies was invented by British scientists Milstein and Kohler in 1975, and won the Nobel Prize in Medicine in 1984 for this. But as far as we know, there is no polyclonal antibody or antibody drug / preparation against PDGFC on the market. Therefore, based on the previous research, we constructed PDGFC polyclonal antibody for the treatment of HPS rats, and it is expected to be used in HPS patients to achieve disease intervention.

[0034] The prepared PDGFC polyclonal antibody was injected into HPS rats by tail vein injection, the single injection dose was 120ml / day / kg, and the administration method of 1ml / kg / day was tail vein administration, such as image 3 Middle A. After three weeks of administration, it was dissected, and the analysis results were as follows:...

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Abstract

The invention discloses an application of a pro-angiogenic factor PDGFC as a marker for diagnosis and treatment of a hepatopulmonary syndrome. The PDGFC carries out up-regulated expression in HPS blood and can be a molecule related to angiogenesis, and the DGFC also has performance of promoting microvascular endothelial cell proliferation, migration and tubule formation, a lung injury score of anHPS group is obviously improved after a PDGFC antibody is given, a DGFC can be used as a drug for promoting lung angiogenesis, and the antibody specifically combined with the PDGFC can be used as a drug for treating the HPS, and is expected to be used for intervention of clinical HPS patients.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of PDGFC, an angiogenesis-promoting factor, as a marker for diagnosing and treating hepatopulmonary syndrome. Background technique [0002] Hepatopulmonary syndrome (HPS) is pathological pulmonary microvascular dilatation (Intrapulmonary vascular dilatation, IPVD), neonatal (Angiogenesis), and severe hypoxemia on the basis of chronic liver disease. Up to 15%, is the main cause of perioperative pulmonary infection and respiratory failure. At present, there is still a lack of effective prevention and treatment methods in clinical practice. [0003] Pathological angiogenesis is one of the core changes in the process of HPS, that is, extensive dilation and neovascularization at the capillary level lead to mismatch between ventilation and perfusion, restricted oxygen exchange diffusion function, and arteriovenous shunt. Smooth muscle cells respond less to endogenous and ex...

Claims

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Application Information

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IPC IPC(8): G01N33/68A61K39/395A61P1/16A61P11/00
CPCG01N33/6893C07K16/22A61P1/16A61P11/00G01N2333/49G01N2800/085G01N2800/12C07K2317/76A61K2039/505
Inventor 杨从文鲁开智易斌刘静
Owner THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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