Application of phospholipase D1 (PLD1) gene and inhibitor thereof in treatment of non-alcoholic fatty liver disease

A non-alcoholic, fatty liver disease technology, applied in medical preparations containing active ingredients, pharmaceutical formulations, digestive system, etc., to achieve a good effect of preventing and treating NAFLD, improving NAFL fat deposition, and improving NASH inflammation and fibrosis.

CN113679840APending Publication Date: 2021-11-23SHANGHAI TONGJI HOSPITAL
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2021-11-23

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Abstract

The invention relates to application of a phospholipase D1 (PLD1) gene and an inhibitor thereof in treating non-alcoholic fatty liver disease. The invention finds that the PLD1 gene can be used as an NAFLD treatment target for the first time, and the PLD1 specific inhibitor can improve NAFLD through a plurality of mechanisms. Research results show that the PLD1 inhibitor can improve liver functions, inhibit serological blood lipid level, inhibit expression of a liver cell lipid droplet formation index SREBP1 and expression of a fatty acid beta oxidation index FASN, inhibit expression of liver cell inflammatory reaction indexes IL-1beta and TNF-alpha, and improve pathological histology of NASH at the same time. The invention finds that the phospholipase D1 can be used as a treatment target of non-alcoholic fatty liver disease for the first time, the PLD1 inhibitor can be researched and developed as a new drug for treating NAFLD, especially NASH, the current situation of lack of NASH treatment drugs in clinic is solved, and the PLD1 inhibitor is expected to be well applied to clinic and has good research and development and application prospects.
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Description

technical field

[0001] The invention relates to the technical field of gene function and application, in particular to the application of a phospholipase D1 (PLD1) gene and its inhibitor in the treatment of non-alcoholic fatty liver disease. Background technique

[0002] With the global prevalence of obesity and its related metabolic syndrome, the incidence of non-alcoholic fatty liver disease (NAFLD) is also increasing. The disease is more common in Western countries, and the adult prevalence is 10% to 30%, and the incidence rate is as high as 57% to 74% in obese people. However, in recent years, the prevalence rate in our country has been close to that of European and American countries, and it is obviously more than viral hepatitis and alcoholic liver disease. Based on epidemiological research data at home and abroad, NAFLD has become a public health problem worldwide. NAFLD is a clinical syndrome characterized by diffuse hepatic macrovesicular steatosis, without a hist...

Examples

Embodiment 1

[0030] Example 1 Experiment of PLD1 inhibitor VU0359595 alleviating liver NAFL in mice

[0031] 1 method:

[0032] 1.1 Grouping

[0033] Forty 6-8 week C57 / BL6 mice were randomly divided into 4 groups, namely normal control group, normal intervention group, high-fat diet (HFD) model group, and HFD model intervention group.

[0034] 2 Intervention methods

[0035] The normal control group and the normal intervention group received a 10% fat diet; the high-fat diet (HFD) model group and the HFD model intervention group received a 60% fat diet for 16 consecutive weeks. The PLD1 inhibitor VU0359595 was administered by intraperitoneal injection, 100nmol / kg, once a day, for 16 consecutive weeks; mice in the normal control group and high-fat diet model group were injected with normal saline, once a day, for 16 consecutive weeks week. At the end of the 16th week, the mice in each group were sacrificed after intraperitoneal anesthesia, eyeball extraction, and blood collection. The co...

Embodiment 2

[0049] Example 2 PLD1 inhibitor VU0359595 alleviates liver NASH in mice

[0050] 1 method

[0051] 1.1 Grouping

[0052] Forty 6-8 week C57 / BL6 mice were randomly divided into 4 groups, namely normal control group, normal intervention group, choline and methionine deficiency (MCD) model group, and MCD model intervention group.

[0053] 1.2 Intervention methods

[0054] The normal control group and the normal intervention group were given MCS diet; the choline and methionine deficiency (MCD) model group and the MCD model intervention group were given MCD diet for 12 consecutive weeks. The PLD1 inhibitor VU0359595 was administered by intraperitoneal injection, 100nmol / kg, once a day, for 12 consecutive weeks; the mice in the normal control group and the choline and methionine deficiency (MCD) model group were intraperitoneally injected with normal saline, daily 1 time for 12 consecutive weeks. At the end of the 12th week, the mice in each group were sacrificed after intraper...