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Application of PEDF gene in treatment on acute drug-induced liver injury

A drug-induced liver injury, drug technology, applied in the field of known gene function and application research, can solve problems such as unclear

Inactive Publication Date: 2018-03-27
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, whether PEDF is involved in acetaminophen-induced acute drug-induced liver injury and whether it is a key molecule in the pathological process of acetaminophen-induced acute drug-induced liver injury is still unclear

Method used

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  • Application of PEDF gene in treatment on acute drug-induced liver injury
  • Application of PEDF gene in treatment on acute drug-induced liver injury
  • Application of PEDF gene in treatment on acute drug-induced liver injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Determination of survival rate of mice induced by acetaminophen

[0036] Littermate female PEDF(- / -) mice, PEDF(+ / -) mice and PEDF(+ / +) mice, 7-8 for each. Animals were fasted without food and water for 12 hours before the start of the experiment. After 12 hours, 750 mg / kg of acetaminophen solution was injected intraperitoneally, and the survival of the animals was recorded every 6 hours until 42 hours after the injection. Survival curves were made, and the significance analysis was performed using the Log-Rank test.

[0037] Acute drug-induced liver injury induced by high doses of acetaminophen can lead to hepatic failure and subsequent death. The determination of the survival rate can reflect the animal's tolerance to acetaminophen. figure 1 is the survival curve of each group of animals induced by acetaminophen, and the results show that the deletion of PEDF gene significantly reduces the survival rate of mice induced by acetaminophen.

Embodiment 2

[0039] Mouse liver pathology detection

[0040] HE staining of liver paraffin sections, the main steps are: baking at 60°C for 30 minutes → xylene (Ⅰ) for 10 minutes → xylene (Ⅱ) for 10 minutes → absolute ethanol (Ⅰ) for 3 minutes → absolute ethanol (Ⅱ) for 3 minutes → 95% ethanol (Ⅰ) for 1 minute → 70% ethanol for 1 minute → distilled water for 2 minutes → hematoxylin solution for 5-10 minutes → running water to wash away hematoxylin for 1-3 seconds → 1% hydrochloric acid alcohol for 1-2 seconds → running water for 20 minutes Minutes → overwash with distilled water for 1-2 seconds → 0.5% eosin for 2 minutes → wash with distilled water for 1 to 2 seconds → 95% ethanol (Ⅱ) for 2 to 3 seconds → absolute ethanol (Ⅲ) for 3 to 5 seconds → Absolute ethanol (IV) for 5-10 seconds → Xylene (I) for 2 minutes → Xylene (II) for 2 minutes → Neutral gum for observation and photography, 100×.

[0041] The pathological section of normal liver tissue showed clear structure of hepatic lobules,...

Embodiment 3

[0043] Detection of serological indicators in mice

[0044] Serum was collected, and commercial kits (Nanjing Jiancheng, C009-2; Nanjing Jiancheng, C010-2) were used to measure the levels of serum alanine aminotransferase and aspartate aminotransferase. The statistical analysis software used SPSS 19.0, and the analysis method used one-way analysis of variance.

[0045] Transaminase is an essential "catalyst" in the metabolic process of the human body. It mainly exists in the liver cells. When the liver cells are damaged, the transaminase in the liver cells will be released into the blood, causing the level of transaminase in the blood to increase. Therefore, through Detection of transaminase levels in blood can indirectly reflect liver damage. Figure 4 It is a graph of serum alanine aminotransferase and aspartate aminotransferase levels in male littermate male PEDF(- / -) mice and PEDF(+ / -) mice treated with acetaminophen or solvent control 6 hours respectively, and the result...

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Abstract

The invention discloses an application of a PEDF gene in treatment on acute drug-induced liver injury. In the present invention, the relationship between the PEDF gene and acute drug-induced liver injury is determined for the first time, and PEDF knockout can exacerbate acetaminophen-induced liver injury. It is determined that the function of the PEDF gene in treatment on acetaminophen-induced acute drug-induced liver injury is mainly reflected in the fact that PEDF has the effect of improving liver injury. PEDF can be used as a drug for the prevention, remission or / and treatment on acute drug-induced liver injury induced by acetaminophen. PEDF can be used as a drug target point for screening drugs for prevention, remission or / and treatment on acetaminophen-induced acute drug-induced liverinjury. PEDF can also be used as a target gene in gene therapy and for the design and preparation of drugs or / and biological preparations for preventing, relieving or / and treating acetaminophen-induced acute drug-induced liver injury.

Description

technical field [0001] The invention relates to the technical field of function and application research of known genes, in particular to the application of PEDF gene in the treatment of acute drug-induced liver injury. Background technique [0002] Acute liver injury refers to liver cell damage that occurs rapidly within a relatively short period of time, and is relatively common in clinical practice. There are many factors leading to acute liver injury, mainly including viral infection, drugs or chemical poisons. Among them, the incidence of drug-induced liver injury caused by drug toxicity increases with the increase of clinical drug types and the increase of the probability of patients changing the dosage of drugs by themselves. [0003] Acetaminophen is a commonly used antipyretic and analgesic drug in clinical practice. Excessive clinical use can lead to severe drug-induced liver injury, and severe cases can lead to liver failure and death. Acetaminophen-induced live...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K48/00A61K38/17A61P1/16
CPCA61K45/00A61K38/1709A61K48/005
Inventor 蔡卫斌李兴会
Owner SUN YAT SEN UNIV
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