Function and application of tumor necrosis factor (TNF) receptor associated factor 1 (TRAF1) in treatment of fatty liver and diabetes mellitus II

A technology for fatty liver and diabetes, which is used in gene therapy, preparations for in vivo experiments, and medical preparations containing active ingredients.

Inactive Publication Date: 2014-10-08
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although other TRAF family members are widely distributed in different tissue cells, TRAF1 mRNA can only be detected in a few tissues such as spleen, lung, and testis

Method used

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  • Function and application of tumor necrosis factor (TNF) receptor associated factor 1 (TRAF1) in treatment of fatty liver and diabetes mellitus II
  • Function and application of tumor necrosis factor (TNF) receptor associated factor 1 (TRAF1) in treatment of fatty liver and diabetes mellitus II
  • Function and application of tumor necrosis factor (TNF) receptor associated factor 1 (TRAF1) in treatment of fatty liver and diabetes mellitus II

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1 Fatty liver and type 2 diabetes model (diet induced obesity, DIO) obtained in mice

[0032] (1) Grouping of experimental animals: 8-week-old, male, WT mice and TRAF1-KO mice were selected and given two special feeds, D12942 high fat diet (High fat diet, HFD) and D12450B low fat diet (Normal chow , NC) feeding, that is, WT NC group, KO NC group, WT HFD group, KO HFD group, a total of 4 groups.

[0033] (2) Operation process of high-fat feed induction model:

[0034] WT and KO mice were used to establish DIO models, and phenotype correlation analysis was performed to clarify the role of TRAF1 gene on fatty liver and type Ⅱ diabetes. 8-week-old, male, WT mice and TRAF1-KO mice were selected and fed with two special diets, D12942 high-fat diet and D12450B low-fat diet, namely WT NC group, KO NC group, WT HFD group, KO HFD group There are 4 groups in total. The food intake of the mice was recorded in detail every week, and the fasting body weight and fasting blo...

Embodiment 2

[0035] Example 2 Determination of mouse body weight and blood glucose level

[0036] (1) Detection of fasting body weight and food intake of mice

[0037] ①Fasting: Fast the mice to be tested at 8:00 am (without water), and start the experimental operation at 2:00 pm.

[0038] ② Weighing: Weigh at 0 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 20 weeks respectively, put a small plastic bucket on the dynamic electronic balance, grab the mouse, and put it into the weighing bucket , measure body weight and record data. Feed amount detection: After the weighing operation is completed, add feed to the mice, and record the amount of feed for the mice on the dynamic electronic balance.

[0039] (2) Fasting blood glucose level detection experiment

[0040] All the mice to be tested were fasted from 8:00 am to 2:00 pm (without water), that is, the experimental operation was started after 6 hours of fasting.

[0041] ① Blood glucose meter preparation: Check the battery of the bl...

Embodiment 3

[0046] Example 3 Intraperitoneal glucose tolerance test (IPGTT)

[0047] On the 18th week of the experiment, the intraperitoneal injection of glucose test (IPGTT) was carried out to evaluate the glucose tolerance of the mice.

[0048] (1) Before measuring blood glucose, measure the fasting body weight of the mice, and calculate the injection volume of glucose based on 10 μL / g.

[0049] (2) First test the fasting blood glucose at 0 minutes before the glucose injection, and inject the glucose solution intraperitoneally quickly after the test is completed.

[0050] (3) Operation method of intraperitoneal injection: ①Fix the mouse; grab the mouse, grasp the tail of the mouse with the little finger and ring finger of the left hand, and grasp the neck of the mouse with the other three fingers, so that the mouse's head is down, and the The abdomen of the mouse is fully exposed. ②Needle positioning and injection: insert the needle from the side of the abdomen, hold the syringe with ...

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Abstract

The invention discloses a function and an application of a tumor necrosis factor (TNF) receptor associated factor 1 (TRAF1) in treatment of a fatty liver and diabetes mellitus II. The function of a TRAF1 gene is researched through a high-fat diet induced model; the weight and the average fasting blood glucose level of a TRAF1 gene knockout mouse raised by a high-fat diet (HFD) are lower than those of a wild type (WT) mouse; the endurance capacity of the TRAF1 gene knockout mouse on glucose is obviously enhanced by a tolerance test of intraperitoneal injection of glucose; a fatty liver disease of the TRAF1-KO mouse in the HFD group is obviously improved by gross appearance of the mouse liver, the liver weight, the liver / weight ratio and the lipid composition pathological staining result; the lipid accumulation is significantly reduced; the TRAF1 gene knockout mouse has the action of significantly improving the fatty liver and the diabetes mellitus II. The TRAF1 can be used as a drug target for screening and treating the fatty liver and / or the diabetes mellitus II aiming at the action, and an inhibitor of the TRAF1 can be applied to preparation of a drug for treating the fatty liver and / or the diabetes mellitus II.

Description

[0001] technical field [0002] The invention belongs to the field of gene function and application, and particularly relates to the application of TNF receptor-related factor 1 (TRAF1) as a drug target in the screening of drugs for the treatment of fatty liver and / or type II diabetes, and the preparation of TRAF1 inhibitors And / or screening of drugs for preventing, alleviating and / or treating fatty liver and / or type 2 diabetes mellitus. Background technique [0003] Diabetes is a chronic metabolic disease that seriously endangers human health. In the past two or three decades, the number of people with diabetes has doubled, and it is an extremely serious threat to human health around the world. In 2010, 285 million people worldwide suffered from diabetes, 90% of whom were type 2 diabetes mellitus (T2DM), and the number of patients is expected to increase to 439 million by 2030, which means that the global 7.7% of adults aged 20-79 will be diabetic. At present, the incide...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/02A61K49/00A61K45/00A61K48/00A61K39/395A61P1/16
Inventor 李红良张晓东汪涛杜成
Owner WUHAN UNIV
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