Application of mPGES-2 as target in treatment or prevention of drug-induced acute liver injury

Abstract

The present invention discloses the application of the mPGES-2 as a target in the treatment or prevention of drug-induced acute liver injury, and belongs to the field of biomedicine. Experiments haveshown that in an acetaminophen-induced mouse acute liver injury model, knockout of the mPGES-2 can significantly reduce ALT and AST levels in the serum, and overexpression of the mPGES-2 can increasethe ALT and AST levels in the serum. This indicates that the mPGES-2 has a regulatory effect on acetaminophen-induced acute liver injury, and the mPGES-2 can be used as a new target for the treatmentor prevention of drug-induced acute liver injury. Knockout of the mPGES-2 can reduce p-JNK and inflammatory responses by inhibiting the oxidative stress, so that acetaminophen-induced acute liver injury can be significantly reduced.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of mPGES-2 as a target in the treatment or prevention of drug-induced acute liver injury. Background technique [0002] Acetaminophen (APAP) is a widely used antipyretic and analgesic drug. Adverse reactions rarely occur at therapeutic doses, but excessive use can lead to necrosis of the hepatic lobules, causing acute liver injury. Acetaminophen is metabolized by the CYP450 enzyme system in the liver, especially CYP2E1, to the toxic product N-acetyl-p-benzoquinone (NAPQI), which interacts with glutathione (GSH) in the liver Rapidly combined to generate a non-toxic metabolite cysteine ​​(cysteine, Cys). When GSH is depleted in hepatocytes, NAPQI covalently binds to mitochondrial proteins, resulting in mitochondrial damage. Damaged mitochondria produce excess reactive oxygen species, release pro-apoptotic factors, and reduce adenosine triphosphate (ATP) produ...

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Problems solved by technology

However, the knockout of mPGES-2 does not reduce the level of PGE2 in the liver, so the expression level and mechanism of mPGES-2 in drug-induced acute liver injury are not clear

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