CN109251956A - The adjustment effect of MyD88 mRNA expression and Radix Astragali in diabetes rat pancreas islet - Google Patents

The adjustment effect of MyD88 mRNA expression and Radix Astragali in diabetes rat pancreas islet Download PDF

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CN109251956A
CN109251956A CN201811097414.5A CN201811097414A CN109251956A CN 109251956 A CN109251956 A CN 109251956A CN 201811097414 A CN201811097414 A CN 201811097414A CN 109251956 A CN109251956 A CN 109251956A
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islet
pancreas
diabetes
expression
myd88 mrna
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冀立霞
姜国辉
刘占涛
高慧
杨志宏
刘超龙
唐振雪
邢丽飞
林雪竹
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Qingdao University
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Abstract

The invention discloses the expression and Radix Astragali adjustment effect of diabetes pancreas islet MyD88 mRNA, the expression of the diabetes pancreas islet MyD88 mRNA gene of STZ induction is obviously increased, the horizontal significant raising of iNOS.Astragalus injection described in prolonged application can not only be such that the expression of T1DM pancreas islet MyD88 mRNA gene lowers, and it is horizontal to can reduce tail of pancreas tissue iNOS.There is obvious apoptosis in T1DM beta Cell of islet, and prolonged application astragalus injection can reverse the tune of T1DM beta Cell of islet to die.The mechanism of action of Astragalus in Treating diabetes can be expressed with pancreas islet MyD88 mRNA is lowered, and reduced tail of pancreas iNOS level, inhibited islet beta-cell apoptosis related.The beneficial effects of the invention are as follows provide certain theoretical foundation for the further the Molecular Biology Mechanism of research onset diabetes mechanism and Astragalus in Treating diabetes.

Description

The adjustment effect of MyD88 mRNA expression and Radix Astragali in diabetes rat pancreas islet
Technical field
The invention belongs to pharmaceutical technology fields, are related to diabetes rat islet tissue MyD88 (Myeloid Differentiation factor marrow sample differentiation factor) mRNA (Messenger ribonucleic acid courier's ribose core Acid) expression and Radix Astragali regulating and controlling effect.
Background technique
Diabetes are a kind of disease of multifactorial inheritance, closely related with patient lifestyle, living environment, have been seriously threatened Human health.The main clinical manifestation that blood glucose rise, diet increase, hydrouria, weight loss are diabetic, is commonly called as: " three-many-one-little ", prolonged illness can involve the multisystems organ such as eye, kidney, peripheral nerve, seriously affect the quality of life of patient, even Threaten the life of patient.The pathogenesis for studying diabetes, seeks the drug of the treatment diabetes of high-efficiency low-toxicity, it has also become current One of critical task of medical field.
Type 1 diabetes (T1DM) are the chronic auto-immune diseases that T cell mediates, it is broken with beta Cell of islet specificity Bad to be characterized, the major way of β cytoclasis is the Apoptosis of immune induction.The generation of T1DM and body autoimmunity are adjusted It is unbalance closely related, after body loses tolerance to a variety of Islet Antigen ingredients, major histocompatibility complex (MHC)-II The bone-marrow-derived lymphocyte antigen that class molecule is handled with it activates Th1 subgroup, inhibition Th2 subgroup in helper lymphocyte T jointly, Pathogenic T h1 cell/cell factor is set to have comparative advantage compared with protectiveness Th2 cell/cell factor, and then activating cytotoxic T Cell, macrophage, natural killer cells generate oxygen radical, nitric oxide, cell factor (IL-1 β, TNF-α, IFN-γ Deng), beta Cell of islet is killed by approach such as NF- κ b, FAS-FASL, eventually leads to the generation of T1DM.
Cell factor IL-1 β, TNF-α are very strong to beta Cell of islet lethality, and IFN-γ helps out, wherein IL-1 β The NO that inducing islet β cell itself generates is great to having an effect for its apoptosis, and prompts to may be by nuclear factor-interleukin 1 receptor (IL-1R) signal transduction pathway plays cytotoxicity.IL-1R once receives to stimulate (IL-1 β, IL-18 etc.) will be with Adaptor protein marrow sample differentiation factor (MyD88) combines, and MyD88 recruits downstream albumen and transmits signal downwards, drops I κ b phosphorylation Solution, and separated with NF- κ b, while NF- κ b is activated into core, with nitricoxide synthase (iNOS Inducible NO synthase) κ b sequence in gene promoter combines, and promotes the transcription of iNOS, generates more NO and mediates β Apoptosis.MyD88 exists at present IL-1R signal pathway transduction still under study for action.
MyD88, a kind of important symbol of previously described bone marrow differentiation are widely present in more than 50 lifes such as the mankind, muroid Species category, the mankind MyD88 assignment of genes gene mapping is in No. 3 chromosome p21.3-p22, 296 amino acid are encoded, MyD88 structure height is protected It keeps, is made of 5 exons and 4 intrones, wherein first exons coding aminoterminal death domain (death Domain, DD), second exons coding intermediate region, last 3 exons codings c-terminus TIR structural domain, these three knots Structure domain constitutes the benchmark architecture of MyD88.Carboxyl terminal has one section of highly conserved sequence, with the TLR of the drosophila and IL-1R of people Certain section of sequence it is very much like, therefore referred to as TIR structural domain.Interaction between MyD88, IL-1R and IL-1RACP is just It is to be realized by the interaction of three's homology TIR structural domain.DD is the knot being made of about 90 amino acid Structure domain interacts between mediating proteins, and the DD structural domain of most of albumen is located at carboxyl terminal, and MyD88, IRAK and fruit DD in the protein pipe of fly is but in amino terminal.The research of MyD88 gene knockout confirms that MyD88 is in TLR/IL-1R signal transduction Center, IL-1R signal transduction is completely dependent on MyD88 to mediate.
Radix Astragali is help class Chinese medicine, is the root of leguminous plant Astragalus membranacus and astragalus mongolicus, and sweet in flavor, slightly warm in nature has and mends The effect of gas lift sun, invigorating qi for consolidating superficies, inducing diuresis to remove edema, promoting pus discharge and tissue regeneration.Radix Astragali mainly contains flavones, polysaccharide, glucoside, amino acid, constant And the Multiple components such as microelement.The effective component of astragalus injection is astragalus polyose, it is to cellular immunity, humoral immunity, non- The activity of specific immune function and cell factor has adjustment effect, while NOD mouse Th1/Th2 type cell can also be inhibited to lose Weighing apparatus state converts the reaction of Th2 type cell/cell factor dominance for the autoimmune response based on Th1 type, for T1DM Prevention and treatment have certain effect.
Summary of the invention
The purpose of the present invention is to provide the expression and Radix Astragali adjustment effect of MyD88 mRNA in glycosuria rat disease pancreas islet, originally Advantageous effect of the invention is further to study the Molecular Biology Mechanism of onset diabetes mechanism and Astragalus in Treating diabetes and mentioning For certain theoretical foundation.
The obvious up-regulation of MyD88 mRNA expression, iNOS level also significantly increase in the diabetic rat pancreas of STZ induction.
Further, prolonged application astragalus injection can not only be such that the expression of T1DM pancreas islet MyD88 mRNA gene lowers, and And it is horizontal to can reduce iNOS in tail of pancreas tissue.
Further, there is obvious apoptosis in T1DM beta Cell of islet, and intraperitoneal injection astragalus injection can partially reverse T1DM pancreas The tune of island β cell is died.
Further, the mechanism of action of Astragalus in Treating diabetes can be expressed with pancreas islet MyD88 mRNA is lowered, and reduce tail of pancreas one Nitric oxide synthase iNOS is horizontal, and the apoptosis for slowing down beta Cell of islet is related.
Detailed description of the invention
Fig. 1 is reverse effect-Electronic Speculum ultra microstructure of the Radix Astragali to diabetes rat islet beta-cell apoptosis.
Specific embodiment
The present invention is described in detail With reference to embodiment.
The research of the invention finds that streptozotocin (streptozotocin, STZ, ip, 55mgkg-1) induction glycosuria The expression of sick rat Langerhans islet MyD88 mRNA gene obviously increases, the horizontal significant raising of iNOS.Prolonged application injects astragalus injection The expression of T1DM pancreas islet MyD88 mRNA gene can not only be made to lower within liquid 21 days (ip, 2.5,5.0ml/kg/d), and can be dropped Low tail of pancreas tissue iNOS is horizontal.Electronic Speculum the result shows that, there is obvious apoptosis, prolonged application astragalus injection in T1DM beta Cell of islet The tune of T1DM beta Cell of islet can be partially reversed to die.The mechanism of action of Astragalus in Treating diabetes may be with downward pancreas islet MyD88 MRNA expression reduces tail of pancreas iNOS level, inhibits islet beta-cell apoptosis related.The following table 1 is Radix Astragali to T1DM blood glucose, serum pancreas Island element and pancreas iNOS influence (n=10,).Table 2 is the influence (n=that Radix Astragali expresses T1DM pancreas islet MyD88 mRNA 10,)。
Table 1
*P < 0.05,**P<0.01vs control group;P<0.05vs T1DM group。
Table 2
*P < 0.05,**P<0.01vs control group;P<0.05vs T1DM group。
Fig. 1 is reverse effect-Electronic Speculum ultra microstructure of the Radix Astragali to diabetes rat islet beta-cell apoptosis.A1 and A2 in Fig. 1 It is normal rats beta Cell of islet, A1 (4.0k)-secretory granules are abundant in Fig. 1, and mitochondria, rough surfaced endoplasmic reticulum (RER) and Gorky are multiple The organelles such as zoarium are intact;A2 (12.0k)-core inner periphery has obvious lumps heterochromatin, and organelle is intact, secretory granules compared with It is more.B1 and B2 is beta cells of isolated rat islets, and lumps heterochromatin disappears in B1 (4.0k)-core, and cytoplasm inner cell organ occurs different The degenerative change of degree, secretory granules, which have no, to be significantly reduced;B2 (15.0k)-mitochondrial cristae fracture, disorder, disappearance, vacuole sample Become;The obvious degranulation of rough surfaced endoplasmic reticulum (RER);The expansion of Golgi complex non-specificity.C1 and C2 is Radix Astragali group (5.0ml/ in Fig. 1 Kg/d) beta cells of isolated rat islets, C1 (4.0k)-core inner periphery reappear lumps heterochromatin, and most of Mitochondrial Shape is just Often.There are still obvious vacuole samples to become for a small amount of mitochondria of C2 (15k)-.
Effect of the present invention research adaptor protein MyD88 in diabetes islet beta-cell apoptosis, and seen using transmission electron microscope The change of beta Cell of islet ultra microstructure is examined, while giving Radix Astragali intervention, observes whether it has reverse immune imbalance, is lowered MyD88 gene expression and the effect of anti-apoptotic.For point for further studying onset diabetes mechanism and Astragalus in Treating diabetes Sub- biological mechanism provides certain theoretical foundation.
The above is only not to make limit in any form to the present invention to better embodiment of the invention System, any simple modification that embodiment of above is made according to the technical essence of the invention, equivalent variations and modification, Belong in the range of technical solution of the present invention.

Claims (4)

1. the expression and Radix Astragali adjustment effect of diabetes pancreas islet MyD88 mRNA, it is characterised in that: the diabetes pancreas islet of STZ induction The expression of MyD88 mRNA gene obviously increases, the horizontal significant raising of iNOS.
2. according to the expression and Radix Astragali adjustment effect of diabetes pancreas islet MyD88 mRNA described in claim 1, it is characterised in that: long Phase can not only be such that the expression of T1DM pancreas islet MyD88 mRNA gene lowers using astragalus injection, and can reduce tail of pancreas tissue Interior iNOS is horizontal.
3. according to the expression and Radix Astragali adjustment effect of diabetes pancreas islet MyD88 mRNA described in claim 2, it is characterised in that: institute It states T1DM beta Cell of islet and obvious apoptosis occurs, prolonged application astragalus injection can partially reverse the tune of T1DM beta Cell of islet It dies.
4. according to the expression and Radix Astragali adjustment effect of diabetes pancreas islet MyD88 mRNA described in claim 2, it is characterised in that: institute The mechanism of action for stating Astragalus in Treating diabetes can be expressed with pancreas islet MyD88 mRNA is lowered, and reduced tail of pancreas iNOS level, inhibited pancreas Island β is apoptosis-related.
CN201811097414.5A 2018-09-18 2018-09-18 The adjustment effect of MyD88 mRNA expression and Radix Astragali in diabetes rat pancreas islet Pending CN109251956A (en)

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CN107243004A (en) * 2017-04-26 2017-10-13 温州医科大学 A kind of application of deoxyschizandrin in medicine preparation

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