CN105854019A

CN105854019A - Application of IL-27 receptor activator to preparation of products for treating obesity and complications thereof

Info

Publication number: CN105854019A
Application number: CN201610298732.2A
Authority: CN
Inventors: 尹芝南; 王倩; 杨恒文
Original assignee: Jinan University
Current assignee: Jinan University
Priority date: 2016-05-06
Filing date: 2016-05-06
Publication date: 2016-08-17

Abstract

The invention belongs to the field of biotechnology and discloses application of an IL-27 receptor activator to preparation of products for treating obesity and complications thereof. IL-27 receptor deficient mice are more prone to obesity than wild type mice, and IL-27 is effective in delaying of an obesity occurrence process. By IL-27 application, body weight growth of obese mice can be effectively inhibited, microphage infiltration in adipose tissues of the obese mice can be effectively relieved, and insulin resistance conditions of the obese mice can be effectively improved.

Description

The application in preparation treatment obesity and complication product thereof of the receptor activators of IL-27

Technical field

The invention belongs to technical field of biology, the receptor activators particularly to a kind of IL-27 is fertile in preparation treatment Application in fat disease and complication product thereof.

Background technology

Obesity is a kind of metabolic disease with accumulation of fat as principal character.Obesity along with a lot of also Send out disease, such as type 2 diabetes mellitus, cardiovascular disease, fatty liver, hypertension, hyperlipidemia, and various tumor Disease.In the past few decades, obesity sharp increase in the world, threaten human health.

Along with increasing year by year and the increase of national health consciousness of obesity, on market fat inhibitor or Slimming medicine is more and more diversified, although is to occur with the form of medicine, but is mostly finally to control consumption The dietary amount of person reaches the purpose of loss of weight.But generally it is attended by the generation of intestinal tract disease or hypoglycemic Undesirable condition occurs.

And from the point of view of for the BMI value Overweight people more than or equal to more than 28, the loss of weight pharmaceutical efficacy failing to understand of going on a diet Aobvious.But employing physical means: excision patient 1/2nd or more stomach etc..Although can be certain Lose weight in degree, but invasive operation is for pursuing the modernization consumer of healthy living, and It it not preferable weight losing method.

In March, 2015, Harvard University Umut Ozcan professor and Research Team thereof find the extraction of a kind of Chinese medicine Composition celastrol can effectively alleviate the Mouse Weight of simulating human obesity, and loss of weight dynamics is up to 50%. But Celastrus orbiculatus Thunb. is as a kind of severe toxicity plant, although Serpentis Caulis et Folium piperis alcohol does not occurs toxic action in mouse experiment, But whether safety still belongs to unknown to the use on human body.

Summary of the invention

In order to overcome existing anti-antiobesic shortcoming of going on a diet or perform the operation with not enough, it is an object of the invention to carry For a kind of IL-27 application in preparation treatment obesity and complication product thereof.

The purpose of the present invention is achieved through the following technical solutions:

The application in preparation treatment obesity and complication product thereof of the receptor activators of IL-27.

The ancillary pathology that the receptor activators of described IL-27 can effectively alleviate obesity and obesity is brought；

IL-27 application in preparation treatment obesity and complication product thereof.

The ancillary pathology that described IL-27 can effectively alleviate obesity and obesity is brought；

Described IL-27 effectively avoids the physical damnification to body as Drug therapy obesity；

One of cytokine that described IL-27 can secrete as human body itself, it is to avoid non-body this Status secretes the impact for the toxic and side effects of body of the medicines such as molecule.

The valid density of described IL-27 is 2～5mg/kg/ days；More preferably 5mg/kg/ days.

The present invention, relative to prior art, has such advantages as and effect:

(1) the IL-27 receptor defected mouse that present invention discover that is more easy to obesity than wild-type mice, and IL-27 Can effectively delay the generation process of obesity, improve because of metabolism such as the fat type 2 diabetes mellitus caused simultaneously The problem that disease effectively solves other scheme:

IL-27 is one of albumen of mononuclear cell secretion in human body, plays an important role in immune system, Not only it is effectively promoted the effect in adaptive immunity of the Th1T cell, simultaneously can also be in self property immunity disease Disease suppresses the secretion of the IL-17 of Th17 (helper T lymphocyte 17, T helper cell 17), thus sends out Wave the attack from autoimmune cell of the protection body.

In the serum of clinical obese people, the expression of IL-27 presents, with normal person compares, becoming of being decreased obviously Gesture, with fat process is negative correlation row.Give fat mouse peritoneal injection IL-27, can effectively press down The fat process of composting, improves because of metabolic problems such as the fat insulin resistants caused simultaneously.

IL-27 albumen can be by successful synthetic, and drug development is already at clinical experimental stage. IL-27 is expected to enter the realization of public people couple as obesity treating medicine, really tests the painless solution of noinvasive The metabolic disease that certainly obesity is brought.

(2) use of IL-27 can effectively suppress the body weight rate of increase of obesity mice；Can effectively delay Solve the macrophages infiltration in adipose tissues；The insulin that can effectively improve obesity mice supports Anti-situation.

Accompanying drawing explanation

Fig. 1 is the result of embodiment 1 small mouse body weight rate of increase.

Fig. 2 is the result of embodiment 2 small mouse body weight rate of increase.

Fig. 3 is the result of macrophage percentage ratio in embodiment 3.

Fig. 4 is the result of embodiment 4 small mouse blood sugar level.

Detailed description of the invention

Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention It is not limited to this.

Implement profit 1:IL-27 receptor knockout mice to be more easy to obesity

Give mice high fat diet and can induce the generation of mice obesity, and knock out little at IL-27 receptor (WSX-1) With Mus (purchased from U.S. Jackson lab), the fat speed of Induced by High Fat Diet and amplitude are significantly increased, knot Fruit sees Fig. 1, IL-27Ra (also referred to as WSX-1) knock out mice (hereinafter referred to as WSX-1KO) and open country Raw type mice (hereinafter referred to as WT) is simultaneously with standard fat feedstuff (hereinafter referred to as SFD) with containing 60%,000 Burnt caloric fat feedstuff (hereinafter referred to as HFD), feeds 6 weeks, monitors weekly the body weight of mice and add up Mouse Weight rate of increase.(in figure, WT SFD represents that WT mice SFD raises, other three groups name classes Seemingly.)

This example demonstrated the important target that IL-27 Receptor signaling pathway is obesity controlling.

Embodiment 2:IL-27 can effectively suppress fat process

After WT mice feeds 4 weeks with HFD, a portion WT mice every other day lumbar injection is recombinated IL-27 (100 μ g/ are only) (hereinafter referred to as rmIL-27), another part WT mice every other day lumbar injection (Phosphate Buffered Saline, PH=7.4, for standard biological buffer, as a control group) for equivalent PBS. Monitored the body weight of mice every 4 days and add up Mouse Weight rate of increase.Result is as in figure 2 it is shown, relative to injection The mice of PBS solution, continues 32 days, and injection rmIL-27 group Mouse Weight growth trend has obtained obvious suppression. This example demonstrated recombinant il-2 7 and can effectively suppress fat process.

Embodiment 3:IL-27 can effectively reduce macrophages infiltration in fatty tissue

Research shows, obesity is the reaction of a kind of chronic low grade inflammation, and the inflammatory factor in fatty tissue is main Deriving from macrophage, macrophage can increase Inflammatory cytokine by suppression Adipocyte Differentiation Expression etc. causes insulin resistant to develop.The present embodiment is by extracting to having injected rmIL-27 1 The epididymis position fatty infiltration lymphocyte of the WT mice of individual month, with F4/80, CD11b fluorescent antibody labelling After macrophage, use Flow cytometry and add up macrophage percentage ratio.Result is as it is shown on figure 3, IL-27 Can effectively reduce macrophages infiltration in fatty tissue, display IL-27 has the relevant chronic inflammatory disease of reduction obesity The potentiality of the diabetes that disease such as insulin resistant causes.

Embodiment 4:rmIL-27 can improve the insulin sensitivity of mice

This enforcement, by insulin clamp period (ITT), gives the most continuously injection rmIL-27 after 1 month WT mice fasting 2～3h pneumoretroperitoneum injection 0.5U/Kg insulin, detects mice by blood glucose meter every 15min Internal blood sugar concentration is to detect the insulin resistant ability of mice.Result as shown in Figure 4, has injected rmIL-27 WT mice in insulin clamp procedure, the sensitivity of insulin is better than control group mice, demonstrate,prove further Clear rmIL-27 can improve the insulin sensitivity of mice.

Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention are not by above-mentioned enforcement The restriction of example, the change made, modifies, replaces under other any spirit without departing from the present invention and principle In generation, combine, simplify, all should be the substitute mode of equivalence, within being included in protection scope of the present invention.

Claims

The application in preparation treatment obesity and complication product thereof of the receptor activators of 1.IL-27.
2.IL-27 application in preparation treatment obesity and complication product thereof.
Application the most according to claim 2, it is characterised in that:

The valid density of described IL-27 is 2～5mg/kg/ days.