CN109576176A - A kind of nanometer selenium bifidobacterium longum and its preparation method and application - Google Patents
A kind of nanometer selenium bifidobacterium longum and its preparation method and application Download PDFInfo
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Abstract
The invention belongs to field of biotechnology, a kind of nanometer selenium bifidobacterium longum and its preparation method and application is specifically disclosed.Application of a kind of nanometer selenium bifidobacterium longum prepared by the present invention in the drug or food that preparation delays diabetes progression, comprising: the metabolism status for improving diabetes physical signs, the pathological change for improving diabetes liver, pancreas and kidney, the drug for improving diabetes serum creatinine and blood urea nitrogen level, prevention diabetic nephropathy or kidney function damage or the application in food.
Description
Technical field
The present invention relates to field of biotechnology, and in particular to a kind of nanometer selenium bifidobacterium longum and preparation method thereof and is making
The standby application delayed in the drug or food of diabetes progression.
Background technique
Bifidobacterium is that one kind can be grown naturally in human gi-tract, and host can be protected to resist virus infection
Bacterium category belongs to Gram-positive, non-athletic property, branch anaerobism Pseudomonas.Bifidobacterium is helped by using as probiotics
Digestion.Before studies have shown that bifidobacterium longum has antitumaous effect as a kind of anaerobic bacteria, to liver cancer cells.Some research reports
Probiotics can work in terms of the metabolic disorder including diabetes in road.
Selenium is basic microelement required for human and animal's health, is mainly played an active part in the form of selenoprotein dynamic
In object physiological processes.It is reported that Selenium Supplement agent can reduce plasma glucose levels in diabetic.Facts proved that
In diabetes patient's body, the stable state metabolism that selenium agent can continue to improve glucose such as adjusts glycolysis to adjust glycometabolism process
With the generation of glucose.There is synergistic effect between insulin and selenium, insulin and selenium synergistic treatment can control diabetes rat
Blood glucose.Epidemic data shows that there are positive correlations between selenium state and diabetes risk.Largely studies have shown that having
For machine selenium compared with inorganic selenium, toxicity is lower, and bioactivity is higher, can be absorbed and utilize rapidly, so it becomes in recent years
Carry out researcher's focus of interest.Current study show that the red elemental selenium of nanometer is exempted from improvement liver protecting, tumor suppression and mouse
It can play a role in terms of epidemic disease function.Selenoprotein plays prevention effect, including cancer, inflammation in certain degenerative disorders
Diseases such as disease property disease, the nervous system disease, aging, infertility and infection etc..Although understanding treatment glycosuria there is presently no complete
The mechanism of disease, but it is now recognized that may be related with the activation of anti-oxidation protection and immune system.The present invention provides a kind of nanometer selenium
Bifidobacterium longum and preparation method thereof and the application in the drug or food that preparation delays diabetes progression.
Summary of the invention
Improvement for solution diabetes existing in the prior art is bad, and easily causes renal function is bad to lack
Point, it is an object of that present invention to provide a kind of nanometer selenium bifidobacterium longums and preparation method thereof, and are applied to preparation and delay sugar
It urinates sick process and improves diabetes physical signs and metabolism status (fasting blood glucose, weight, serum insulin level, glucose
Tolerance test, food intake dose, water intake and urine volume etc.), improve diabetes insulin signal path, improve diabetes liver,
Pathological change, prevention diabetic nephropathy or the kidney function damage of pancreas and kidney improve diabetes serum creatinine and blood
The drug or food of urea nitrogen levels.
Nanometer selenium bifidobacterium longum disclosed by the invention delay diabetes progression and improve diabetes physical signs and
Metabolism status, the pathological change for improving diabetes insulin signal path, improving diabetes liver, pancreas and kidney, prevention sugar
It urinates sick renal complications or kidney function damage, the drug of improvement diabetes serum creatinine and blood urea nitrogen or the application on food leads to
Following technology solution is crossed to further realize:
A kind of preparation method of nanometer selenium bifidobacterium longum, includes the following steps:
(1) red nano selenium element is dissolved in TPY culture medium, obtains the TPY culture medium containing nanometer selenium；
(2) bifidobacterium longum bacterium solution is inoculated into the TPY culture medium of above-mentioned nanometer selenium, obtains nanometer selenium-Bifidobacterium
TPY culture medium；
(3) it is long double to be obtained into nanometer selenium based on being incubated overnight in incubator for the TPY culture of above-mentioned nanometer selenium-Bifidobacterium
Discrimination bacillus.
Preferably, the concentration of nanometer selenium is 1~10g/mL in the TPY culture medium described in step (1) containing nanometer selenium.
Preferably, the mass ratio of bifidobacterium longum bacterium solution and TPY culture medium is 1:20~30 in step (2).
Preferably, the condition cultivated in step (3) are as follows: 37 DEG C of constant temperature incubations, until OD600 value is not less than 0.2.
Preferably, nanometer selenium is enriched on bifidobacterium longum, and the size of the nanometer selenium is 40~44nm.
Beneficial effects of the present invention:
(1) present invention compares protective effect of three kinds of Bifidobacteriums to diabetes, the i.e. long bifid of bifidobacterium longum, selenium-rich
Bacillus, rich nanometer selenium bifidobacterium longum (i.e. nanometer selenium bifidobacterium longum), the results showed that nanometer selenium bifidobacterium longum is to diabetes
The protective effect effect of mouse is best, and the mouse fasting blood glucose being administered through nanometer selenium bifidobacterium longum is lower, weight gain, serum
Insulin level is higher；Glucose tolerance tests (IPGTT) horizontal reduction；The 8 of diabetes model are caused at streptozotocin (STZ)
During week, nanometer selenium bifidobacterium longum also reduces the metabolism status such as 24 hours food intakes, water intake and urine volume, this knot
Fruit illustrates that nanometer selenium bifidobacterium longum can prevent diabetic hyperglycemia.
(2) it after normal mouse receives the nanometer selenium bifidobacterium longum of maximum dose, compared with normal mouse, does not show
Difference is write, shows the good safety of nanometer selenium bifidobacterium longum.
(3) nanometer selenium bifidobacterium longum can protect blood glucose and renal function caused by the diabetes induced as STZ,
Its protective effect is due to caused by the change of insulin signaling pathway, and insulin signaling pathway controls the glucose of liver cell
Transhipment, insulin successively activate insulin receptor and substrate 1 in conjunction with the insulin receptor of target cell surface
(IRS1), to recruit three kinases of phosphoinositide (PI3K), in hepatic glucose intake, an important target protein of PI3K
It is Protein Kinase B (AKT/PKB).The present invention the result shows that, compared with model group (STZ induction after mouse), nanometer selenium is long
Bifidobacterium has raised the expression of p-IRS1 and p-AKT, lowers the expression of p-GSK-3 β, and the up-regulation of p-IRS1 and p-AKT can mention
The intake of high glucose reduces plasma glucose levels.Therefore, nanometer selenium bifidobacterium longum passes through enhancing insulin signal transduction
Approach improves the sensibility of insulin, reduces blood glucose level.
(4) present invention also measures the level of creatinine in serum (Scr) and urea nitrogen (BUN), to test it to renal function
Influence.Diabetes can cause serious health problem, including big blood vessel and microvascular complication, and one of which is renal tissue
Damage, will lead to renal insufficiency, after STZ diabetes-induced 8 weeks, it may appear that the index of some renal damages, such as urea nitrogen
Increase.Present invention discover that nanometer selenium bifidobacterium longum shields in the kidney in STZ inducing mouse.Nanometer selenium is long double
Discrimination bacillus can reduce the harm of renal insufficiency by reducing mice serum urea nitrogen and kreatinin, reduce Pathological disease
Become.In the present invention, using STZ inducing mouse diabetes model is used after long-term stomach-filling nanometer selenium bifidobacterium longum, as a result, it has been found that receiving
Rice selenium bifidobacterium longum can play a protective role in the breaking-out of the diabetes and renal function that delay STZ to induce.
(5) present invention in nanometer selenium bifidobacterium longum administration after, in diabetes model liver and Pancreas pathology damage into
Exhibition speed slows down.
(6) the present invention provides a kind of medicines for preparing economic, feasible, preparation that is working well and delaying diabetes progression
The method of object or food.
1. Detailed description of the invention
Fig. 1 is the comparison of the influence of bifidobacterium longum, selenium bifidobacterium longum and nanometer selenium bifidobacterium longum to blood glucose；
Wherein, normal group of 1- (not injecting STZ)；2- model group (injection STZ)；3- nanometer selenium bifidobacterium longum；4- selenium is long
Bifidobacterium；5- bifidobacterium longum；Mouse measures fasting in -1w, 1w, 2w, 3w, 4w, 5w, 6w, 7w, 8w respectively after injecting STZ
Blood glucose level (n=8)；(##P < 0.01,###P < 0.001, compared with normal group；* p < 0.01 p < 0.05, * *, with model group phase
Than)；
Interpretation of result: bifidobacterium longum, selenium bifidobacterium longum and the bacterium solution stomach-filling 1 of three kinds of nanometer selenium bifidobacterium longum are given
Month, then use STZ inducing mouse diabetes model.Protective effect of the nanometer selenium bifidobacterium longum to diabetes are caused as the result is shown
Effect is best.Compared with model group, the fasting blood glucose level of nanometer selenium bifidobacterium longum processing is minimum.Therefore it is selected in subsequent experimental
Nanometer selenium bifidobacterium longum is selected to study the influence to diabetes.
Fig. 2 be mouse inject STZ after respectively in fasting blood-glucose (A), the weight of -1w, 1w, 2w, 3w, 4w, 5w, 6w, 7w, 8w
(B) and STZ injection after 8 weeks mouse serum insulin level (C) situation；
Wherein, normal group of 1- (not injecting STZ)；2- model group (injection STZ)；3- low dose group；4- middle dose group；5- high
Dosage group；6- toxicity test group (n=8)；(##P < 0.01,###P < 0.001, compared with normal group；* p < 0.01 p < 0.05, * *, with
Model group is compared)；
Interpretation of result: since blood glucose level is the gold standard of diabetes subclinical inflammation, so it is long to have evaluated nanometer selenium
Effect of the Bifidobacterium to the STZ blood glucose in diabetic mice induced, the present invention also have evaluated the weight of experiment mice, as a result, it has been found that
Compared with model group mouse, the mouse of long-time stomach-filling nanometer selenium bifidobacterium longum shows obviously nanometer selenium bifidobacterium longum group
Reduced fasting blood glucose level (Fig. 2A) and higher weight (Fig. 2 B)；Because internal glucose balance is mainly by insulin tune
Section, the present invention also has detected concentration of the insulin in serum, compared with model group mouse, the empty stomach of administration group (3,4,5,6)
Insulin level is higher (Fig. 2 C).
Fig. 3 is that influence of the nanometer selenium bifidobacterium longum to internal glucose balance is compared；
Wherein, normal group of 1- (not injecting STZ)；2- model group (injection STZ)；3- low dose group；4- middle dose group；5- high
Dosage group；6- toxicity test group.By the dosage of 1.0g/kg to mouse peritoneal injectable dextrose monohydrate, detected every specific time interval
Glucose level (every group of 3 mouse)；(###P < 0.001, compared with normal group；* p < 0.01 p < 0.05, * *, with model group phase
Than)；
Interpretation of result: the present invention has inquired into influence of the nanometer selenium bifidobacterium longum to internal glucose balance.It is tried in IPGTT
In testing, the glucose level of model group mouse is in significant downward trend (Fig. 3), this shows that it is administered in nanometer selenium bifidobacterium longum
Afterwards, the clearing amount of glucose increases.
Fig. 4 is that influence of the nanometer selenium bifidobacterium longum to mouse metabolism situation is compared；
Wherein, normal group of 1- (not injecting STZ)；2- model group (injection STZ)；3- high dose group；4- middle dose group；5- is low
Dosage group；6- toxicity test group；Fig. 4 A: the food intake dose of mouse；Fig. 4 B: water intake；Fig. 4 C: urine volume；(##P < 0.01,###P<
0.001, compared with normal group；* p < 0.01 p < 0.05, * *, compared with model group)；
Interpretation of result: compared with normal group that does not inject STZ, 24 hours food for injecting the model group mouse of STZ is taken the photograph
Enter amount, water intake and urine volume to increase obviously.Moreover, from dosage, 24 hours food intake dose, water intake and urine
The amount relationship negatively correlated with the increase of nanometer selenium bifidobacterium longum dosage.
Fig. 5 is that (H&E is dyed for effect of the nanometer selenium bifidobacterium longum to liver and pancreatic tissue form；20×10)；
Wherein, normal group of 1- (not injecting STZ)；2- toxicity test group；3- model group (injection STZ)；4- low dose group；5-
Middle dose group；6- high dose group；Fig. 5 A: the pathology of hepar slice map of mouse；Fig. 5 B: mice pancreatic pathology slice
Figure；
Interpretation of result: the Histological results of liver and pancreas show between nanometer selenium bifidobacterium longum and model group
There is significant difference, after the administration of nanometer selenium bifidobacterium longum, pathological analysis is carried out by HE, such as Fig. 5 A, in normal group and poison
Without apparent pathological lesion in property test group；In model group, liver cell oedema, endochylema is loose, and as nanometer selenium is long double
The increase of discrimination bacillus dosage, lesion degree gradually weaken, visible a small amount of inflammatory cell in the tissue of model group, with nanometer
The increase of selenium bifidobacterium longum dosage, the degree of infiltrating inflammatory cells are weakened.It is normal to organize mouse and toxicity test such as Fig. 5 B
Group mouse does not have apparent pathological change；Only observe that pancreas contains a small amount of fatty vacuole in high dose group；Low middle dose group
It was found that acinus arrangement in part is loose other than fatty vacuole.As the dosage of nanometer selenium bifidobacterium longum increases, the disease of pancreas
Change degree gradually weakens.Generally speaking, after the administration of nanometer selenium bifidobacterium longum, the tempo of liver and Pancreas pathology damage
Slow down.
Fig. 6 is that influence of the nanometer selenium bifidobacterium longum to insulin signaling pathway is compared；
Wherein, Western blotting is analyzed in hepatic tissue: Fig. 6 A:p-IRS1；Fig. 6 B:pGSK-3 β；Fig. 6 C:pAKT
Protein level, respectively with the ratio of total IRS1, GSK-3 and AKT；Normal group of 1- (not injecting STZ)；2- toxicity test group；3- is low
Dosage group；4- middle dose group；5- high dose group；6- model group (injection STZ) (#P < 0.05, compared with normal group；* p < 0.05,
Compared with model group, p < 0.05)；
Interpretation of result: insulin signaling pathway plays a crucial role in the homeostasis of glucose, therefore, is
The molecular mechanism of research nanometer selenium bifidobacterium longum prevention diabetes glucose, the signal that the present invention has studied hepatic insulin are logical
Road, result of study is as shown in Fig. 6 A, 6B and 6C, and compared with model group, the expression of p-IRS1 and pAKT dramatically increase in liver,
And the expression of pGSK-3 β substantially reduces, the expression enhancing of insulin signaling pathway GAP-associated protein GAP, this demonstrate nanometer seleniums
Bifidobacterium longum can effectively improve the sensibility of the signal of liver insulin.
Fig. 7 is protective effect of the nanometer selenium bifidobacterium longum to renal function；
Wherein, normal group of 1- (not injecting STZ)；2- model group (injection STZ)；3- low dose group；4- middle dose group；5- high
Dosage group；6- toxicity test group；Fig. 7 A: the H&E coloration result of kidney；Fig. 7 B: the urea nitrogen levels of serum；Fig. 7 C: serum flesh
Acid anhydride level (##P < 0.01, compared with normal group；* p < 0.05, compared with model group)；
Interpretation of result: the function of kidney is mainly influenced by kidney duct and glomerulus, and nephridial tissue inspection shows visible in tissue
Part renal tubular necrosis, the light dye of epithelial cell endochylema, karyopycnosis followed by organize in visible glomerulus blister cavities disappear, sphere and capsule
Wall is adhered, proliferation of mesangial cells；Proliferation of mesangial cells and glomerulus atrophy with the increase of nanometer selenium bifidobacterium longum dosage and
Gradually weaken (Fig. 7 A)；The processing of nanometer selenium bifidobacterium longum is compared with model group mouse, serum urea nitrogen (Fig. 7 B) and urine
Creatinine (Fig. 7 C) is horizontal to be reduced.The above result shows that nanometer selenium bifidobacterium longum can improve the kidney function impaired because of diabetes
Energy.
Specific embodiment
With reference to embodiment, further statement in detail is made to the present invention:
Embodiment 1
(1) preparation of bacterium solution
Bifidobacterium longum is that the TPY culture medium at 37 DEG C carries out Anaerobic culturel: red nano selenium element is dissolved in
In the TPY culture medium of 200mL, ultimate density is that (concentration for having attempted nanometer selenium is respectively 1,2.5,5,7.5,10g/ to 5g/mL
ML, effect are close)；Then, bifidobacterium longum bacterium solution is taken out from 4 DEG C of refrigerator, in parts by mass, bifidobacterium longum bacterium
Liquid measure: culture medium=1:25 is inoculated into new TPY culture medium and (has attempted the matter of bifidobacterium longum bacterium solution amount Yu TPY culture medium
Amount is more close than respectively 1:20,1:22.5,1:25,1:27.5,1:30, effect), it is put into 37 DEG C of constant incubators and trains overnight
It supports, until OD600 value reaches 0.2, in case next day stomach-filling uses；Finally, collect culture bacterial strain, then with 5% glucose
Physiological saline cleans 3 times, and the centrifugal condition of cleaning is 3500rpm, at 4 DEG C, 5min；Collected bacterium solution is resuspended in 0.1mL's
In milk, intragastric administration on mice is given.Control group gives 13% skim milk of 100 μ L/only.
(2) foundation of diabetic mice
The male mice (C57BL/6J) of 4-5 week old is purchased from the Nanjing animal pattern research institute of Nanjing University, and mouse is every
Its stomach-filling bacterium solution, after continuous gavage 25 days, mouse fasting 12 hours, free water injected the cold lemon for being dissolved in 0.1M in continuous 5 days
In the STZ solution (50mg/kg) of acid buffering (pH=4.5), control group mice injects citrate.It is surveyed after 3 days using blood glucose meter
Mouse fasting blood glucose level is measured, monitors the blood glucose level and weight of mouse weekly, as a result as shown in Figure 1.
(3) compare the effect of three kinds of bifidobacterium longums
To illustrate protective effect of the nanometer selenium bifidobacterium longum to diabetic mouse model, the present invention by bifidobacterium longum,
Selenium bifidobacterium longum as two comparative examples, compares, and be compared the protective effect of diabetic mouse model therewith
Explanation.Bacterium solution 0.1mL is given once daily in every mouse, and the stomach-filling time is 4w.50 mouse are randomly divided into 5 groups, wherein control
Group: normal group；Model group: the diabetic mice of STZ induction；Wild type bifidobacterium longum, selenium bifidobacterium longum, nanometer selenium are long double
Discrimination bacillus: 3.0 × 10 are given respectively before the diabetic mice modeling of STZ induction10The bacterium solution stomach-filling of a/kg.
(4) dose dependent effect of nanometer selenium bifidobacterium longum
Nanometer selenium-bifidobacterium longum 0.1mL is given once daily in every mouse, and the stomach-filling time is 4w, and 60 mouse are divided at random
It is 6 groups, grouping is respectively normal group, model group, Bifidobacterium low dose group (0.75 × 1010A/kg), middle dose group (1.5 ×
1010A/kg), high dose group (3.0 × 1010A/kg), toxotest group (3.0 × 1010A/kg stomach-filling normal mouse)；STZ
In the 3rd day to 8 weeks after injection, the blood glucose level and weight (such as Fig. 2) of mouse are monitored.Mouse is put into mouse metabolism cage,
Collect the mouse intake, water of food and urine volume (such as Fig. 4) for 24 hours.At the end of experiment, the water of blood serum Bun and BUN is measured
It is flat.Wherein, serum insulin level is measured using mouse islets element ELISA kit.When STZ is injected the 8th week, in glucose
In tolerance test, after mouse overnight starvation, be injected intraperitoneally glucose (1.0g/kg), 0 after injection, 15,30,60,90min from
Tail vein takes blood respectively, and detects blood-sugar content (such as Fig. 3) with blood glucose meter.
Mouse liver is put into rapidly liquid nitrogen for future use.Hepatic tissue is homogenized in cell pyrolysis liquid, cracks 30min on ice
Afterwards, it is centrifuged 10min, centrifugal condition 12000rpm, 4 DEG C, collects supernatant, and with Coomassie Brilliant Blue (Bradford method)
Protein concentration is detected, protein concentration is adjusted, 5 × loading buffer is added and simultaneously boils sample 5min in boiling water bath, sample is placed in-
It is saved backup at 20 DEG C.With anti-IRS1, anti-pIRS1, anti-GSK-3, anti-pGSK-3, anti-AKT and anti-
PAKT antibody is marked.Quantified using Image J software.
(5) histologic analysis method
Using the morphological change of HE decoration method observation liver, pancreas and kidney, liver, pancreas and renal tissue are placed in
It is fixed in the paraformaldehyde that concentration is 4% to stay overnight；Routine paraffin wax embedding, 5 μm of slices；Slice is conventional to be dewaxed with dimethylbenzene, through each
Grade ethyl alcohol is extremely washed.5min is respectively impregnated in dimethylbenzene I, dimethylbenzene II to transparent, dehydration conditions are as follows: dehydrated alcohol I, anhydrous second
Alcohol II, 95% alcohol, 80% alcohol, 75% alcohol, each 5min.Indigo plant is returned in flowing water flushing after haematoxylin redyes 2min, originally water logging
Steep 15min or warm water (about 50 DEG C) 5min.Yihong liquid 2min is set, tap water rinses.Dehydration conditions are as follows: 75% alcohol, 80% wine
Essence, 95% alcohol, dehydrated alcohol I, each 5min of dehydrated alcohol II.5min is respectively impregnated in dimethylbenzene I, dimethylbenzene II to transparent, is dried in the air
Dry 3min.Mounting method: resinene mounting is added dropwise in tissue, then takes clean coverslip, is carefully added in mounting medium
On, it slowly flattens, keeps cover plate position moderate.Microscopically observation, simultaneously long-term preservation (such as Fig. 5 and Fig. 7) of taking pictures.
The present invention also attempt document it has been reported that Bifidobacterium conventional medicine or food making method and drug or
Food formulation method is applied to nanometer selenium bifidobacterium longum, also all produces and preferably delays diabetes progression and improvement glycosuria
Physiological pathology index and metabolism status, the pathology for improving diabetes insulin signal path, improvement diabetes liver, pancreas and kidney
Variation, prevention diabetic nephropathy or kidney function damage, the effect for improving diabetes serum creatinine and blood urea nitrogen；This hair
It is bright also attempt as routine treating diabetes or prophylactic agent or food, by nanometer selenium bifidobacterium longum by with conventional sugar
Urine disease treats or prevents drug or food and treatment method use in conjunction, can further increase treating diabetes or pre- preventive effect
Fruit.
Particular embodiments described above has carried out further in detail the purpose of the present invention, technical scheme and beneficial effects
It describes in detail bright, it should be understood that the above is only a specific embodiment of the present invention, is not intended to restrict the invention, it is all
Within the spirit and principles in the present invention, any modification, equivalent substitution, improvement and etc. done should be included in guarantor of the invention
Within the scope of shield.
Claims (10)
1. a kind of preparation method of nanometer selenium bifidobacterium longum, which is characterized in that
(1) red nano selenium element is dissolved in TPY culture medium, obtains the TPY culture medium containing nanometer selenium；
(2) bifidobacterium longum bacterium solution is inoculated into the TPY culture medium of above-mentioned nanometer selenium, obtains nanometer selenium-Bifidobacterium TPY
Culture medium；
(3) the TPY culture of above-mentioned nanometer selenium-Bifidobacterium is obtained into the long bifid bar of nanometer selenium based on being incubated overnight in incubator
Bacterium.
2. a kind of preparation method of nanometer selenium bifidobacterium longum according to claim 1, which is characterized in that in step (1)
The concentration of nanometer selenium is 1~10g/mL in the TPY culture medium containing nanometer selenium；Bifidobacterium longum bacterium solution and TPY in step (2)
The mass ratio of culture medium is 1:20~30；The condition cultivated in step (3) are as follows: 37 DEG C of constant temperature incubations, until OD600 value is not less than
0.2。
3. the nanometer selenium bifidobacterium longum of preparation according to the method for claim 1, which is characterized in that nanometer selenium is enriched in length
On Bifidobacterium, the size of the nanometer selenium is 40~44nm.
4. a kind of nanometer selenium bifidobacterium longum according to claim 3 delays in diabetes progression drug or food in preparation
Application.
5. a kind of nanometer selenium bifidobacterium longum according to claim 3 improves diabetes physical signs and metabolism shape in preparation
The drug of condition or the application in food, the diabetes physical signs and metabolism status are fasting blood glucose, weight, serum islet
One of plain level, glucose tolerance test, food intake dose, water intake and urine volume are a variety of.
6. a kind of nanometer selenium bifidobacterium longum according to claim 3 improves diabetes insulin signal path in preparation
Application in drug or food.
7. a kind of nanometer selenium bifidobacterium longum according to claim 3 improves diabetes liver, pancreas and kidney in preparation
Pathological change drug or the application in food.
8. a kind of nanometer selenium bifidobacterium longum according to claim 3 improves diabetes serum creatinine and plasma wrea in preparation
The drug of nitrogen level or the application in food.
9. a kind of nanometer selenium bifidobacterium longum according to claim 3 is in preparation prevention diabetic nephropathy or kidney function
The application in drug or food that can be damaged.
10. a kind of nanometer selenium bifidobacterium longum according to claim 3 treats or prevents medicine in preparation and conventional diabetes
The application of object or food conjunctive use delayed in diabetes progression drug or food.
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| CN112391318A (en) * | 2020-11-25 | 2021-02-23 | 广州态和生物科技有限公司 | Preparation method of bifidobacterium longum and selenium-enriched microorganism and preparation method of freeze-dried preparation thereof |
| CN113755409A (en) * | 2021-10-28 | 2021-12-07 | 南昌大学 | Bifidobacterium longum for relieving insulin resistance and application thereof |
| CN116585360A (en) * | 2023-05-24 | 2023-08-15 | 微康益生菌(苏州)股份有限公司 | Probiotic agent for improving chronic kidney disease and application thereof |
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