CN103006641A - Application of alpha-zinc sulfate in preparing medicament for treating diabetes mellitus complication - Google Patents
Application of alpha-zinc sulfate in preparing medicament for treating diabetes mellitus complication Download PDFInfo
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- CN103006641A CN103006641A CN201210576767XA CN201210576767A CN103006641A CN 103006641 A CN103006641 A CN 103006641A CN 201210576767X A CN201210576767X A CN 201210576767XA CN 201210576767 A CN201210576767 A CN 201210576767A CN 103006641 A CN103006641 A CN 103006641A
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Abstract
The invention discloses application of alpha-zinc sulfate in preparing a medicament for treating diabetes mellitus complication. Application results indicate that expression of AGT (angiotensinogen) can be remarkably increased by high glucose. Furthermore, high glucose can activate expression of other gene expression of RAS (renin-angiotensin system) in 3T3-L1 adipocytes, including rennin, AGT, ACE (angiotensin converting enzyme), AT1R (angiotensin ii type 1 receptor), AT2R (angiotensin ii type 2 receptor), and reduce expression of renin-binding protein in contrast. High glucose can remarkably increase oxidative stress caused by reactive oxidative species; and expression of rennin and ACT can be reduced by applying antioxidant alpha-lipoic acid and reducing the level of reactive oxidative species, so that the application of alpha-zinc sulfate can be used in preparation of a medicament for treating nephropathy and hypertension complicated by diabetes mellitus.
Description
Technical field
The present invention relates to biomedicine field, be specifically related to the application of α-zinc sulfate in the diabetes complicated disease drug of preparation treatment.
Background technology
The nearly all chronic complicating diseases of diabetes is all relevant with renin-angiotensin system (RAS), but feritin is not found in the diabetics blood in research or Angiotensin II increases to some extent, and the component of RAS does not only raise in the circulation, even descends.Along with many tissues comprise the discovery of expressing each composition of RAS in pancreatic tissue, fatty tissue, the heart tissue, it is found that the RAS of histiocyte part plays an important role in the generating process of diabetic complication.
High sugar causes that oxidative stress is the initial sum center mechanism of chronic complicating diseases of diabetes morbidity.Cellular Oxidation stress and raise along with the glucose level increase, and the gene expression of the local RAS component of while cell is activated, and research finds that blocking oxide stress reduce the RAS activation level, blocks RAS and also can reduce the ROS generation.In part blocking-up RAS effect, do not reduce the RAS related gene in the expression of part.
Summary of the invention
The object of the invention is to the relation according to high sugar and local RAS, provide a kind of antioxidant in the diabetes complicated disease drug of preparation, to use.
In fact, the present invention relates to the application of alpha-lipoic acid in the diabetes complicated disease drug of preparation.
Relate to the application of alpha-lipoic acid in preparation diabetic complication nephropathy medicine.
Relate to the application of alpha-lipoic acid in preparation diabetic complication hypertension drug.
The below proves its application in pharmaceutical field with pharmacological evaluation and the result of alpha-lipoic acid.
Grouping experiment is carried out in the 3T3-L1 adipose cell strain of differentiation and maturation:
(1) 5.5mM sugar concentration: the adipose cell of differentiation and maturation is divided into 3 groups, contains in the DMEM culture fluid of 0.2%BSA hungry 12 hours at serum-free.The adipose cell of differentiation and maturation is divided into 2 groups, and 1 group is the serum-free DMEM culture fluid contrast of 5.5mM sugar concentration, and other 1 group of serum-free DMEM culture fluid that adds the 5.5mM sugar concentration that contains the a-thioctic acid was cultivated 48 hours;
(2) 15mM sugar concentration: the adipose cell of differentiation and maturation is divided into 3 groups, contains in the DMEM culture fluid of 0.2%BSA hungry 12 hours at serum-free.The adipose cell of differentiation and maturation is divided into 2 groups, and 1 group is the serum-free DMEM culture fluid contrast of 15mM sugar concentration, and other 1 group of serum-free DMEM culture fluid that adds the 15mM sugar concentration that contains the a-thioctic acid was cultivated 48 hours;
(3) 25mM sugar concentration: the adipose cell of differentiation and maturation is divided into 3 groups, contains in the DMEM culture fluid of 0.2%BSA hungry 12 hours at serum-free.The adipose cell of differentiation and maturation is divided into 2 groups, and 1 group is the serum-free DMEM culture fluid contrast of 25mM sugar concentration, and other 1 group of serum-free DMEM culture fluid that adds the 25mM sugar concentration that contains the a-thioctic acid was cultivated 48 hours.
The result:
Different sugar concentration is on the impact of the local RAS gene expression of 3T3-L1 adipose cell
Induce the 3T3-L1 cell of differentiation and maturation to comprise 5.5mM in different sugar concentration, 15mM, the effect of 25mM concentration of glucose is after 48 hours, the variation of feritin, RBP, proangiotensin, Angiotensin-Converting, AT1R, AT2R gene expression dose: compare with 5.5mM sugar concentration group, the 15mM concentration of glucose can reduce the protein-bonded expression of feritin in the 3T3-L1 adipose cell significantly, and feritin, proangiotensin, angiotensin converting enzyme, AT1R, AT2R are expressed and are the trend that increases, but not statistically significant.Feritin, proangiotensin, angiotensin converting enzyme, AT1R, AT2R express and significantly increase in the 25mM glucose group, increase respectively 51.71 times (F=170.7, P＜0.0001) than the 5.5mM glucose group, 12.86 (F=31.56 doubly, P＜0.0001), 3.04 times (F=7.132, P=0.0037), 4.16 (F=5.167 doubly, P=0.0118), 2.62 times (F=3.698, P=0.0349), and feritin further is reduced to 76.3%(F=8.548, P=0.001 in conjunction with egg).This shows that high glucose concentration can increase feritin, proangiotensin, angiotensin converting enzyme, AT1R, AT2R expression, thereby activates the RAS system.
Different sugar concentration is on the impact of 3T3-L1 adipose cell ROS
Induce the 3T3-L1 cell of differentiation and maturation to comprise 5.5mM in different sugar concentration, 15mM, the effect of 25mM concentration of glucose is the expression of ROS in the cell after 48 hours: 15mM glucose and 25mM glucose all can significantly increase the expression of ROS in the cell, with 5.5mM glucose matched group than increasing respectively 141.1% and 198.5%(F=22.36, P＜0.0001).
Antioxidant is on the impact of ROS in the cell and each composition expression of RAS
Change the impact that each composition of RAS is expressed for ROS under the clear and definite high glucose concentration, we add the antioxidant alpha-lipoic acid inducing to break up completely in the 3T3-L1 adipose cell, cultivate the variation that detects ROS in the 3T3-L1 adipose cell, feritin, RBP, proangiotensin, Angiotensin-Converting, AT1R, AT2R expression after 48 hours.Alpha-lipoic acid can significantly reduce the interior ROS to 69.1%(t=3.184 of cell that the 25mM glucose causes, P=0.008).And under 5.5mM glucose group and 15mM concentration of glucose condition, alpha-lipoic acid does not make significant difference to intracellular ROS.
In 5.5mM glucose group and 15mM glucose group, alpha-lipoic acid is expressed feritin, angiotensinogen mRNA and is changed without significance.In the 25mM glucose group, after giving alpha-lipoic acid and processing, feritin, angiotensinogen mRNA are expressed and are down to respectively original 43.8%(t=3.953, P=0.002), 43.5%(t=2.803, P=0.013), and have significant difference.In 15mM glucose group and 25mM glucose group, alpha-lipoic acid all has significant reducing effect (t=2.803, P=0.013) to RBP.Alpha-lipoic acid changes all without significant change Angiotensin-Converting, AT1R, AT2R under the different sugar concentration conditions.
Result of the present invention shows that high sugar can increase the expression of AGT significantly.In addition, high sugar can also activate the expression of other each genes of RAS in the 3T3-L1 adipose cell, comprises feritin, AGT, and ACE, AT1R, AT2R, the expression of opposite RBP reduces.Simultaneously, hyperglycemia is showing the increase reactive oxygen species, the oxidative stress that causes.Use the antioxidant alpha-lipoic acid and can reduce the expression of feritin and ACT by reducing the reactive oxygen species level, thereby can be used for diabetes complicated nephropathy and the preparation of hypertensive medicine.
The specific embodiment
Embodiment
(1) 5.5mM sugar concentration: the adipose cell of differentiation and maturation is divided into 3 groups, contains in the DMEM culture fluid of 0.2%BSA hungry 12 hours at serum-free.The adipose cell of differentiation and maturation is divided into 2 groups, and 1 group is the serum-free DMEM culture fluid contrast of 5.5mM sugar concentration, and other 1 group of serum-free DMEM culture fluid that adds the 5.5mM sugar concentration that contains the a-thioctic acid was cultivated 48 hours;
(2) 15mM sugar concentration: the adipose cell of differentiation and maturation is divided into 3 groups, contains in the DMEM culture fluid of 0.2%BSA hungry 12 hours at serum-free.The adipose cell of differentiation and maturation is divided into 2 groups, and 1 group is the serum-free DMEM culture fluid contrast of 15mM sugar concentration, and other 1 group of serum-free DMEM culture fluid that adds the 15mM sugar concentration that contains the a-thioctic acid was cultivated 48 hours;
(3) 25mM sugar concentration: the adipose cell of differentiation and maturation is divided into 3 groups, contains in the DMEM culture fluid of 0.2%BSA hungry 12 hours at serum-free.The adipose cell of differentiation and maturation is divided into 2 groups, and 1 group is the serum-free DMEM culture fluid contrast of 25mM sugar concentration, and other 1 group of serum-free DMEM culture fluid that adds the 25mM sugar concentration that contains the a-thioctic acid was cultivated 48 hours.
With respect to the LG group, middle glucose group and the intracellular active oxygen of high glucose group all have significance to increase.Feritin, proangiotensin, Angiotensin-Converting, hypertensin 1 receptor, hypertensin 2 receptor all have significance to increase in the high glucose group, and middle glucose group also shows identical trend but non-significant difference.And RBP all significantly reduces in middle glucose group and high glucose group; The increase of the reactive oxygen species that antioxidant α-zinc sulfate high sugar capable of blocking causes, thereby the increase that the feritin that the blocking-up high glucose is induced and AGT express.
The above is preferred embodiment of the present invention, but the present invention should not be confined to the disclosed content of this embodiment.So everyly do not break away from the equivalence of finishing under the spirit disclosed in this invention or revise, all fall into the scope of protection of the invention.
Claims (3)
1. the application of alpha-lipoic acid in the diabetes complicated disease drug of preparation treatment.
2. the application of alpha-lipoic acid in preparation treatment diabetic complication nephropathy medicine.
3. the application of alpha-lipoic acid in preparation treatment diabetic complication hypertension drug.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108354161A (en) * | 2018-05-30 | 2018-08-03 | 广东永青生物科技有限公司 | The applicable sweetener being made of fructose of one group of diabetic population |
| CN114028358A (en) * | 2021-12-03 | 2022-02-11 | 锦州福寿堂医药科技有限公司 | Lipoic acid soft capsules for treating diabetes and complications thereof, and preparation method and application thereof |
-
2012
- 2012-12-26 CN CN201210576767XA patent/CN103006641A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| 《中国医学创新》 20120331 罗健华 alpha-硫辛酸对糖尿病防治的研究进展 第163-164页 1-2 第9卷, 第8期 * |
| 《国际内科学杂志》 20090831 李艳英等 alpha-硫辛酸治疗2型糖尿病及其并发症的研究进展 第468-470、475页 1-3 第36卷, 第8期 * |
| 李艳英等: "α-硫辛酸治疗2型糖尿病及其并发症的研究进展", 《国际内科学杂志》 * |
| 罗健华: "α-硫辛酸对糖尿病防治的研究进展", 《中国医学创新》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108354161A (en) * | 2018-05-30 | 2018-08-03 | 广东永青生物科技有限公司 | The applicable sweetener being made of fructose of one group of diabetic population |
| CN114028358A (en) * | 2021-12-03 | 2022-02-11 | 锦州福寿堂医药科技有限公司 | Lipoic acid soft capsules for treating diabetes and complications thereof, and preparation method and application thereof |
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Application publication date: 20130403 |