CN101693104A - New application of thymic peptide-5 - Google Patents

Abstract

The invention discloses a new application of thymic peptide-5 and relates to thymic peptides. Animal experiments prove that the thymic peptide-5 can remarkably enhance the carbohydrate tolerance of a mouse and remarkably resist the generation of diabetes of a STZ-induced mouse. A tissue slice shows that the thymic peptide-5 plays an important role in islet cell structure protection; therefore, the thymic peptide-5 can be used for maintaining the normal glycometabolism, protecting islet cell structures and preparing medicines for preventing and treating diabetes.

Description

The new purposes of thymic peptide-5

Technical field

The present invention relates to a kind of thymosin, especially relate to a kind of new purposes of thymic peptide-5.

Background technology

The clinical practice of thymosin starts from 20th century the mid-1970s, its topmost contribution is to the thymus dependent treatment of diseases, it is for keeping PID, autoimmune disease and cancer patient's immunoreactivity, stimulate the lymphocytic activity of its specificity to play main effect, therefore be widely used in diseases such as therapy system lupus erythematosus, Behcet's syndrome, rheumatoid arthritis, severe infection, bronchial asthma, acute, chronic hepatitis and tumor.In addition, because human wearing out reflects the atrophy of thymic tissue and the depletion of function significantly, thymosin can be postponed the appearance of some Senile disease, therefore using the thymosin defying age also has extremely wide prospect ([1] Goldstein AL, Garaci E.Combination Therapiess[M] .New York:springer, 1993:39-48; [2] Liu Zhijun, Lv Junling, Tian Guotao, etc. thymosin progress and clinical practice [J]. capital medicine, 2003,10 (10): 40; [3] Bela B, Bela BJ, Stuart E, et al.Review ofthymic hormones in cancer diagnosis and t reament[J] .Int J Immunopharma, 2000,22 (4): 261).

Along with going deep into of research, people have turned to research emphasis the single peptide in the thymosin, in the hope of finding more effective clinical treatment medicine.

" thymic peptide-5 " (TP-5) is made up of arginine, lysine, aspartic acid, valine and tyrosinase 15 seed amino acid, and its structure is as follows: H ₂N-Arg-Lys-Asp-Val-Tyr-OH, chemical name: N-[N-[N α-[N α-L-arginyl-L-lysyl]-L-α-aspartoyl]-the L-valyl]-the L-tyrosyl.Structural formula: Arg-Lys-Asp-Val-Tyr, molecular formula: C30H49N9O9.TP-5 has immune two-ways regulation function, has inducing and promotes the T lymphocyte and subgroup differentiation, maturation and activatory function, regulates the lymphocytic ratio of T, makes CD4+/CD8+ be tending towards normal; Regulate and strengthen the effect of human body cell immunologic function, can impel the T lymphocyte maturation in the peripheral blood after mitogen activates, increase the T cell in various antigens or the former secretion that activates the various lymphokines in back (as: α, IFN-, interleukin-22 and interleukin-13) of mitogenesis, increase the level of lymphokine receptor on the T cell.It strengthens lymphocyte reaction by the activation to t helper cell simultaneously.May influence the chemotactic of NK precursor in addition, this precursor becomes after being exposed to interferon more cytotoxicity, helps bringing into play its therapeutical effect.The someone uses the thymic peptide-5 treatment and accompanies the type ii diabetes patient of immunologic hypofunction at present.

The major reason and the autoimmune disease of type i diabetes are closely related, wherein mainly be because beta Cell of islet is subjected to the attack of autoimmune cell, cause antigen-exposed, cause that immune system further reacts, make beta Cell of islet lose in a large number, normal secretion of insulin is affected, and blood sugar increasing forms diabetic symptom.STZ (streptozotocin) is used widely in the preparation of type i diabetes model, rat under the disposable ejection situation of 50mg/kg and can modeling success, mice then reaches the modeling purpose after the injection at same dose through 5 times continuously substantially, think that at present the mechanism of action of STZ is by making body produce excessive N O, attack and destroy beta Cell of islet, cause that pancreatic island cell antigen exposes, activation immunity of organism mechanism, thereby a large amount of macrophages enter the damage of islet cells aggravation islet cells, cause insulin secretion to reduce at last, cause that blood glucose increases, and brings out diabetes.Inductive mouse thymus atrophy, the obvious enlargement of kidney, and serum oxidation resistance ([4] Liu Zhangqing that significantly descends, Song Lijiang, Jiang Dongsheng is etc. the influence to the mice diabetes model of-streptozotocin stability. practical preventive medicine, 2008,15 (3): 896-897; [5] Wu Qinghong, Gu Weiwang, Yuan advances. and streptozotocin is induced and is set up the type i diabetes rat model. animal medicine progress, 2006,27 (8): 114-116).

In recent years, the cause of disease of diabetes and study of pathogenesis show the generation of oxidative stress and diabetes and develop closely related ([6] Cao Wenbin etc. the antioxidation micronutrient is prevented and treated the progress of diabetes. Changchun University of Traditional Chinese Medicine's journal, 2006,22 (2): 73-74), in order to prevent developing of diabetes, people have the natural anti-reflecting oxide of preventing and treating the diabetes effect to some and have carried out systematic research, find that they interrupt the vicious cycle that oxidation invasion and attack cause the beta Cell of islet infringement by expressing different mechanism with the effect link, thereby provide a new strategy for natural anti-oxidation treatment diabetes.

So far do not see the relevant report of relevant thymic peptide-5 in the function of blood sugar regulation and protection islets of langerhans.

Summary of the invention

The object of the present invention is to provide a kind of new purposes of thymic peptide-5.

Confirm that by zoopery thymic peptide-5 can obviously strengthen the carbohydrate tolerance effect of mice, and can obviously resist the generation of STZ inducing mouse diabetes.Tissue slice finds that TP-5 plays an important role for protection islet cells structure, so thymic peptide-5 can be used for keeping normal carbohydrate metabolism, and protection islet cells 26S Proteasome Structure and Function can be used for preparing the prevent diabetes medicine.

By experimental results show that in the animal body; TP-5 has the generation of the inductive diabetes of good opposing STZ; show the influence of good opposing diabetes-induced factor; and possesses the function that strengthens the carbohydrate tolerance effect; the Electronic Speculum ultrastructure is the result prove; TP-5 is obvious at protection thymus structure and islets of langerhans configuration aspects effect; and facilitation is arranged also aspect islet secretion; it is tight to be embodied in the thymocyte cell structure; structure of mitochondria is clear, and ridge shape structure is obvious, and the appearance of matched group thymus structure is misaligned; phenomena of apoptosis is obvious; structure of mitochondria is fuzzy, and coming off appears in ridge shape structure, and cavity appears in the circular secretory granule dense granule of islets of langerhans topology discovery matched group; and medication group dense granule is many, and the cavity phenomenon is not obvious.The result proves that TP-5 has important protective effect in the generation of opposing diabetes, lay the foundation for developing diabetes genetic engineering potential drug from now on.

Description of drawings

Fig. 1 induces the effect (TP-5 and STZ inject simultaneously) of diabetes to mice opposing STZ for subcutaneous injection TP-5.

Fig. 2 is the effect of subcutaneous injection TP-5 to AUC.

Fig. 3 is the influence of subcutaneous injection TP-5 to carbohydrate tolerance.

Fig. 4 is TP-5 processed group thymus Electronic Speculum figure.

Fig. 5 is TP-5 processed group thymus Electronic Speculum figure.

Fig. 6 is matched group thymus Electronic Speculum figure.

Fig. 7 is matched group thymus Electronic Speculum figure.

Fig. 8 is matched group islets of langerhans Electronic Speculum figure.

Fig. 9 is TP-5 processed group islets of langerhans Electronic Speculum figure.

The specific embodiment

Following examples will the present invention is further illustrated in conjunction with the accompanying drawings.

The materials and methods that embodiment adopted is described as follows.

Experiment is drawn materials and mainly biological reagent is as follows:

Experimental animal is the C57BL/6 mice, and (20 ± 2) g is male age in 6-7 week, the SPF level, and 60 of mices are provided by Shanghai Slac Experimental Animal Co., Ltd., the quality certification number: SCXK (Shanghai) 200320003.Kunming mouse, male SPF level is provided by Xiamen University zooscopy center.Single cage is fed, 18～25 ℃ of room temperatures, and relative temperature 50%～80%, illumination every day 12h freely ingests, drinks water.

Streptozotocin (streptozotocin STZ, SIGMA.USA), lot number 053K1569; Citric acid (Chengdu letter He Huagongshijichang), lot number: 20040821.Blood-sugar detecting instrument is the Llifscan of Johson ﹠ Johnson product and supporting detection reagent paper.

Below provide 2 embodiment.

Embodiment 1

20 C57BL/6 mices are equally divided into 2 groups, and 10 every group, 1 group of subcutaneous route is given TP-5, organizes in contrast with the equal volume citrate buffer solution for one group.Lumbar injection STZ in the time of administration once a day, presses 50mg/kg dosage, continuous 4 days, inject STZ certainly after, the 5th, 20 and 30 day tail vein surveyed blood glucose.The results are shown in Table 1 and Fig. 1,4～9.

Table 1 subcutaneous injection TP-5 induces the effect (TP-5 and STZ inject simultaneously) (C57BL/6 mice) of diabetes to mice opposing STZ

^*: compare P＜0.05, significant difference with matched group; ^*: compare with matched group, P＜0.01 difference is extremely remarkable.

Embodiment 2

20 kunming mices are equally divided into 2 groups, and 10 every group, 1 group of subcutaneous route is given TP-5, organizes in contrast with the equal volume citrate buffer solution for one group.Continuous 14 days, carried out carbohydrate tolerance and test in the 14th day.The results are shown in Table 2 and Fig. 2 and 3.

Table 2 subcutaneous injection TP-5 is to strengthening the effect (kunming mice) of mice carbohydrate tolerance effect

^*: compare P＜0.05, significant difference with matched group; ^*Compare with matched group, difference is extremely remarkable.

The carbohydrate tolerance experiment is calculated as follows:

AUC＝0.25×(BS?value?at?0hour+4×BS?value?at?0.5?hours+3×BS?value?at?2hours)。

This is tested all data and carries out analyzing and processing by SPSS (version 13.0, SPSS Inc.) software.

Thymic peptide-5 is provided by Hainan Zhonghe Medicine Co., Ltd, the 1mg/ bottle, and selecting kunming mice and C57BL/6 mice is laboratory animal, the subcutaneous injection administration is verified the physiological function of this medicine.

The experimental technique of a kind of new function of TP-5 may further comprise the steps:

1) by the subcutaneous injection approach thymic peptide-5 is pressed 10 a μ g/ dosed administration;

2) claimed the mice body weight every 5 days;

3) survey mice fasting glucose and carry out the carbohydrate tolerance experiment after 14 days;

4) the hypodermic while of TP-5, mice once a day, is pressed 50mg/kg dosage through lumbar injection STZ, continuous 4 days, inject STZ certainly after, at the 5th day, blood glucose was surveyed in 20 days and 30 days.

Claims (1)

1. thymic peptide-5 is used to prepare the prevent diabetes medicine.

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