Functions and application of TNF (tumor necrosis factor) receptor associated factor 5 (TRAF5) in treatment of fatty liver and type 2 diabetes mellitus

A technology for fatty liver and diabetes, used in gene therapy, medical preparations containing active ingredients, antibodies, etc.

Inactive Publication Date: 2014-09-24
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that TRAF5 knockout mice can reduce blood-brain barrier (BBB) ​​damage and inflammation, thereby protecting the injury caused by cerebral ischemia-reperfusion (4); TRAF5 plays a role in aortic arch constriction-induced It plays an important role in cardiac hypertrophy (5), but the role of TRAF5 in fatty liver and diabetes has not been reported

Method used

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  • Functions and application of TNF (tumor necrosis factor) receptor associated factor 5 (TRAF5) in treatment of fatty liver and type 2 diabetes mellitus
  • Functions and application of TNF (tumor necrosis factor) receptor associated factor 5 (TRAF5) in treatment of fatty liver and type 2 diabetes mellitus
  • Functions and application of TNF (tumor necrosis factor) receptor associated factor 5 (TRAF5) in treatment of fatty liver and type 2 diabetes mellitus

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Fatty liver and type 2 diabetes model (diet induced obesity, DIO) obtained in mice

[0036] (1) Grouping of experimental animals: 8-week-old, male, WT mice and TRAF5-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.

[0037] (2) Operation process of high-fat feed induction model:

[0038] WT and KO mice were used to establish DIO models, and phenotype correlation analysis was performed to clarify the role of TRAF5 gene on fatty liver and type Ⅱ diabetes. 8-week-old, male, WT mice and TRAF5-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

[0039] Example 2 Determination of mouse body weight and blood glucose level

[0040] (1) Fasting body weight and food intake detection of mice

[0041] ①Fasting: Fast the mice to be tested at 8:00 am (without water), and start the experimental operation at 2:00 pm.

[0042] 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.

[0043] (2) Fasting blood glucose level detection experiment

[0044] 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.

[0045] ① Blood glucose meter preparation: Check the battery of the blood...

Embodiment 3

[0050] Example 3 Intraperitoneal glucose tolerance test (IPGTT)

[0051] 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.

[0052] (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.

[0053] (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.

[0054] (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 functions and application of TNF (tumor necrosis factor) receptor associated factor 5 (TRAF5) in treatment of fatty liver and type 2 diabetes mellitus. Studies on a TRAF 5 gene by a high-fat diet (HFD) induced model discover that both the body weight and fasting plasma glucose level of an HFD bred TRAF gene knock-out mouse are lower than those of a WT mouse; glucose tolerance tests by intraperitoneal injection discover that the glucose tolerance of the TRAF5 gene knock-out mouse is remarkably reinforced; results of on liver gross appearance, liver weight, liver/body weight ratio and lipid component pathological staining indicate that the TRAF5-KO mouse fatty liver lesion in the HFD group is remarkably improved, the lipid accumulation is remarkably reduced, and the TRAF5 gene knock-out has the effects of remarkably improving fatty acid and type-II diabetes mellitus. Against the effects, the TRAF5 gene knock-out can be used as a medicinal target for screening and treating fatty liver and/or type-II diabetes mellitus, and the inhibitor of the TRAF5 gene knock-out can be used for preparing medicaments for treating fatty liver and/or type-II diabetes mellitus.

Description

technical field [0001] The invention belongs to the field of gene function and application, and in particular relates to the application of a TNF receptor-associated factor 5 (TRAF5) as a drug target in the screening of drugs for the treatment of fatty liver and type II diabetes, and the preparation and / or application of TRAF5 inhibitors Or screening of drugs for the prevention, alleviation and / or treatment of fatty liver and type 2 diabetes. Background technique [0002] With the increase of aging population, urbanized life and changes in lifestyle, obesity, non-alcoholic fatty liver disease, metabolic syndrome and diabetes and other metabolic abnormalities have increased sharply, and have now become an important hazard to global public health. 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....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K48/00A61K39/395A61P3/10A61P1/16
Inventor 李红良张晓东汪涛杜成
Owner WUHAN UNIV
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