CN116327813A - Application of lactobacillus zoon in preparing medicament for treating depression - Google Patents
Application of lactobacillus zoon in preparing medicament for treating depression Download PDFInfo
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- CN116327813A CN116327813A CN202310016490.3A CN202310016490A CN116327813A CN 116327813 A CN116327813 A CN 116327813A CN 202310016490 A CN202310016490 A CN 202310016490A CN 116327813 A CN116327813 A CN 116327813A
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Abstract
The invention discloses application of lactobacillus animalis in preparation of a medicament for treating depression. The application of the animal lactobacillus in preparing the medicament for treating the depression can use the animal lactobacillus as an auxiliary medicament for treating the depression, the animal lactobacillus can relieve depression-like behaviors of depressed rats, improve hippocampal neurons of the depressed rats, improve intestinal flora diversity, recover intestinal flora disorder caused by stress, improve the abundance of enterococcus faecalis, improve the content of intestinal butyric acid and reduce the occurrence risk of inflammatory bowel diseases.
Description
Technical Field
The invention belongs to the technical field of microorganisms, and particularly relates to application of lactobacillus animalis in preparation of a medicament for treating depression.
Background
Depression is a major clinical feature with significant and persistent emotional depression. Currently, more than 3.5 million people worldwide suffer from depression, and the incidence rate continues to rise in recent years. The antidepressant drugs widely used in clinical treatment at present, such as selective serotonin reuptake inhibitors (Selective Serotonin Reuptake Inhibitor, SSRI) have the defects of slow onset of action, inconsistent therapeutic effect, large side effect and the like, so that the treatment of the depression has serious limitations. Dietary supplements and probiotic therapy are an attractive means to achieve positive mental health and to prevent the development of symptoms of mental diseases and related conditions.
The gut-brain axis describes the bi-directional communication that exists between the brain and the gut, while the microbe-gut-brain axis supports the role of the gut microbiome in this communication system. There is increasing evidence that the gut microbiota has profound effects on brain physiology, psychological response and final behaviour. Emerging evidence suggests that probiotics can affect central nervous system function and regulate mood, psychological symptoms (such as anxiety and depression), and changes in physiological, behavioral and brain functions that are related to stress.
Probiotics have been widely accepted by consumers as dietary supplements. At present, most of researches on the function of probiotics are focused on improving the gastrointestinal functions, regulating the nutrition metabolism and the immunity, and the like. Numerous scientific studies and clinical experiments have demonstrated that probiotics have a significant improving effect on constipation, enteritis, lactose intolerance, anti-infection, inflammation, allergy, and glycolipid metabolic disorders. Along with the gradual maturation of the theory of 'brain intestinal axis', the intestinal flora is regulated by probiotics so as to improve the nerve function, and the method becomes a new means for treating depression. The regulatory effects of certain bifidobacteria and lactobacilli on neurological function have also been demonstrated by animal studies and clinical studies.
Disclosure of Invention
The invention aims to provide an application of lactobacillus plantarum in preparing a medicament for treating depression.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the first aspect of the invention provides an application of lactobacillus animalis in preparing medicaments for treating depression.
The lactobacillus zoon is a bacterial suspension.
The Lactobacillus plantarum can be prepared into pharmaceutical preparations.
The dosage form of the pharmaceutical preparation is at least one selected from powder, tablets, granules, capsules and solutions.
The administration mode of the medicine is oral administration.
The Lactobacillus plantarum is Lactobacillus plantarum JCM 5670 with a collection number of CGMCC 1.2623.
The pharmaceutical formulation also includes other pharmaceutically acceptable carriers.
The other pharmaceutically acceptable carrier comprises at least one of excipient, binder, diluent, disintegrating agent, filler, wetting agent, absorption enhancer, surfactant, adsorption carrier, and lubricant.
The excipient is at least one selected from lactose, microcrystalline cellulose, mannitol and starch.
The adhesive is at least one selected from methyl cellulose, ethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose and hydroxypropyl methylcellulose.
The diluent is at least one selected from calcium sulfate, dextrates, dextrin, monosaccharide or polysaccharide, kaolin, sugar alcohol and microcrystalline cellulose.
The disintegrating agent is at least one selected from dry starch, sodium carboxymethyl starch, low-substituted cellulose, polyvinylpyrrolidone, sodium carboxymethyl cellulose, microcrystalline cellulose, potassium polyacrolein, sodium starch glycolate and low-substituted hydroxypropyl cellulose.
By adopting the technical scheme, the invention has the following advantages and beneficial effects:
the application of the animal lactobacillus in preparing the medicament for treating depression can use the animal lactobacillus as an auxiliary medicament for treating depression, through establishing a depression rat model and experiments of grouping feeding of the animal lactobacillus, the comparison of the syrup preference experiment, tail suspension experiment and behavioral evaluation of forced swimming experiment of a depression group and the lactobacillus group shows that the gavage animal lactobacillus can obviously raise the level of syrup preference percentage (P < 0.001), obviously shorten the tail suspension immobility time (P < 0.001) of rats and obviously reverse the trend of swimming immobility time (P < 0.001), thereby proving that the animal lactobacillus can lighten depression-like behavior of depressed rats, and through microscopic examination of hippocampus slices of rats, the CA1 area cone cells of the rat hippocampus CA1 area of the rats have a larger improvement effect, the cone cells are orderly arranged, and the Nitype small bodies in the cells thereof are clearly visible, thereby proving that the animal lactobacillus can improve the neurons of the depressed rats.
Drawings
Fig. 1 is a graph showing the effect of sugar water preference (Mean SEM, n=6) for rats of each experimental group. **** P<0.001, compared with the blank control group, #### P<0.001, compared to the model set.
Fig. 2 is a graph showing the effect of tail suspension immobility time (Mean SEM, n=6) for each experimental group of rats. **** P<0.001, compared with the blank control group, #### P<0.001, compared to the model set.
Fig. 3 is a schematic representation of immobility time (Mean SEM, n=6) of rats of each experimental group in forced swimming experiments. **** P<0.001, compared with the blank control group, #### P<0.001, compared to the model set.
FIG. 4 is a schematic representation of the results of a rat ipsilateral hippocampal CA1 zone Nitype stain (. Times.20). A is a model group; b is a blank control group; c is a probiotic group.
Detailed Description
In order to more clearly illustrate the present invention, the present invention will be further described with reference to preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and that this invention is not limited to the details given herein.
Example 1
Lactobacillus animalis was able to reduce the depression-like behaviour in rats:
1. establishment of chronic stress model and animal grouping
The experimental animals were 18 male SD rats, and the body weight was about 200 g. After one week of acclimation, animals were randomly divided into 3 groups of 6 animals each, a placebo group, a depressive model group, and a probiotic group, respectively.
The probiotics group adopts Lactobacillus plantarum, lactobacillus subspecies JCM 5670, china general microbiological culture collection center.
And establishing a chronic depression model by adopting an internationally recognized CUMS scheme and a solitary culture mode. The blank group received no stimulus other than the behavioral evaluation. The depression model group and the probiotic group received chronic stress stimulation for 6 weeks, once daily, each stimulation not repeated within two consecutive days. The stress factors used in the experiment include: the wet padding is 20h, the 45-degree inclined mouse cage is 24h, the binding is 2h, the cold water swimming is performed at 4 ℃ for 5min, the mouse cage is vibrated for 15min, the tail is clamped for 1min, the water is forbidden for 24h, and the fasted food is fasted for 24h.
Blank control group: no cure stimulation was received, and the control solvent was infused once daily from 2 weeks post-molding to the end of the experiment. Depression model group: CUMS stimulation was received and the control solvent was infused once daily from 2 weeks post-molding to the end of the experiment. Probiotic group: after 2 weeks from molding, the stomach 10 is irrigated while molding 9 cfu live lactobacillus 0.2ml was infused once daily to the end of the experiment.
2. Behavioural evaluation method
(1) Sugar water preference experiment: during the adaptation stage before the experiment, the rats are trained in syrup, 2 bottles of 1% syrup are simultaneously put in each cage and maintained for 3 days, then 1 bottle of 1% syrup is changed, the other bottle of pure water is maintained for 4 days, and the positions of 1% syrup and pure water are changed every day. Rats were then subjected to sugar water preference experiments on day 0 (week 0) and day 42 (week 6) of molding. Before the experiment, a bottle of 1% syrup and a bottle of pure water are simultaneously administered to the rat in the experiment, the detection time is 1h, the detection is usually carried out at 19:00-20:00, the volumes of the syrup and the pure water before and after the experiment are measured, the drinking volume and the total drinking volume of the two are respectively calculated, and the percentage of the syrup drinking volume to the total drinking volume is the syrup preference percentage.
(2) Tail suspension experiment (TST): tail suspension experiments were performed on day 43. The part of the fixed rat, which is 2cm away from the tail end, is positioned on the horizontal rod, and the head of the rat is hung to be 5-6cm away from the horizontal plane, so that the sight of the adjacent rats is separated. Each rat was hung for 6min, and its cumulative immobility time was recorded over the last 4min, after each experiment was completed, the rats were returned to their respective cages. The criteria for determining tail suspension were: the rats forgo struggling and the body hangs vertically in the air.
(3) Forced Swimming Test (FST): the forced swimming experiment was performed the following day after the end of the tail-suspension experiment. The rats were individually placed in a bucket with a water depth of about 35cm and a temperature of 25 ℃ to force them to swim for 6min, the total immobility time in the last 4min was recorded, and after each experiment was completed, the rats were wiped dry and returned to their cages. The rats were stationary or slightly shaky in the water to maintain a floating state, and were regarded as stationary.
(4) Statistical analysis was used: statistics and mapping were performed using GraphPad Prism 5 (us GraphPad Software company), and comparisons between sets of data were performed using one-way analysis of variance (ANOVA) and further pairwise comparisons between sets were performed using Tukey test.
3. Results display
(1) As shown in fig. 1, fig. 1 is a graph showing the effect of sugar water preference (Mean SEM, n=6) of rats of each experimental group. **** P<0.001, compared with the blank control group, #### P<0.001, compared to the model set. After 6 weeks of stimulation in the model group and 4 weeks of gastric lavage treatment with 6 weeks of stimulation in the probiotic group, the percentage of sugar water preference was significantly reduced in rats in the depressed model group compared to the placebo group (P<0.001 A) is provided; while the probiotic group was able to significantly increase the level of sugar water preference percentage compared to the depression model group (P<0.001). This suggests that lactobacillus in the gavage animals can improve the behavior of the CUMS rats for lack of pleasure.
(2) As shown in fig. 2, fig. 2 is a graph showing the effect of tail suspension immobility time (Mean SEM, n=6) for each experimental group of rats. **** P<0.001, compared with a blank control group, #### P<0.001, compared to the model set. Compared with the blank control group, the 6-week stimulation significantly prolongs the tail suspension immobility time (P in all of the rats in the depression model group<0.001 A) is provided; compared with the depression model group, the probiotic group can obviously shorten the tail suspension immobility time (P)<0.001). The results indicate that the Lactobacillus animalis has an improved extension of the CUMS-induced tail suspension immobility time in rats.
(3) As shown in fig. 3, fig. 3 is a schematic diagram of immobility time (Mean SEM, n=6) of each experimental group of rats in forced swimming experiments. **** P<0.001, compared with the blank control group, #### P<0.001, compared to the model set. Compared with the blank control group, the swimming immobility time of the depression model group is obviously prolonged (P respectively<0.001 A) is provided; compared with the depression model group, the probiotics group can obviously reverse the trend of prolonged swimming immobility time (P<0.001). This suggests that lactobacillus animalis can improve the behavior of CUMS in inducing prolonged forced swimming immobility in rats.
Example 2
Effects of Lactobacillus animalis on depressed rat hippocampal neurons:
the rat hippocampal samples were sliced and Nitype stained: that is, after behavioral evaluation, one rat was taken for each group, and anesthesia was performed by 20% uratam (0.4 mL/100 g) by intraperitoneal injection, the chest was rapidly opened and the heart was completely exposed, the needle was inserted into the left ventricle, the right auricle was cut off, the abdominal active vein was clamped, 150mL of PBS was injected to rapidly perform pressure infusion to flush the blood until the outflow from the right auricle was substantially clear, and the infusion was stopped, at which time the rat lung, eyeball and paw were observed to be white. Then 200mL of 4% paraformaldehyde was rapidly poured under pressure. At this time, taking the stiffness of the upper limb and the head of the rat as a sign, stopping pouring, taking the brain after head breakage, and fixing the brain tissue in 4% paraformaldehyde for 48 hours as soon as possible after the brain tissue is obtained through coronal surface material. The fixed tissue was dehydrated with ethanol from low concentration to high concentration in this order, 50% ethanol (2 h) → 75% ethanol (2 h) → 85% ethanol (2 h) → 95% ethanol (1 h) → 95% ethanol (2 h) → absolute ethanol (1 h) → absolute ethanol (1.5 h). Then transparent in xylene, first cylinder 1h, second cylinder 1h. Embedding with paraffin with melting point of 52-60deg.C, transferring transparent brain tissue into melted paraffin for paraffin soaking, first cylinder (1 h), and second cylinder (2 h). The paraffin of about 2mm around the brain tissue is reserved, after the superfluous paraffin is trimmed by a blade, the tissue is sliced to be 5 mu m thick, the temperature of the slice is 45 ℃, and the sliced slice is put into a slice baking machine at 60 ℃ for 2h for baking. Paraffin sections were dewaxed in xylene for 5min each in the first, second and third cylinders, followed by rinsing with tap water for 1min each in absolute ethanol, 95% ethanol, 85% ethanol, 75% ethanol for 5 min. The sections were placed in 1% toluidine blue water solution and stained in an incubator at 56 ℃ for 20min, and washed clean with distilled water. After about 1min of differentiation with 70% ethanol, differentiation with 95% ethanol was performed, and the mixture was subjected to mirror control, with the Nib's body showing clarity, the absolute ethanol was rapidly dehydrated, and xylene was transparent and sealed.
The results are shown in FIG. 4, and FIG. 4 is a schematic representation of the results (. Times.20) of the on-hippocampal CA1 region of rats. A is a model group; b is a blank control group; c is a probiotic group. Compared with a blank control group, the arrangement of vertebral cells in the CA1 region of the rat hippocampus in the depression model group is disordered, the cell gap is increased, the Nitype corpuscles in the cell bodies are reduced or completely disappeared, and the cells are contracted; compared with a depression model group, the vertebral cells in the CA1 region of the hippocampus of the rat in the probiotics group are orderly arranged, the Nitype bodies in the cells are clearly visible and approach to a blank control group, and the animal lactobacillus is indicated to inhibit the depression activity of a depression rat induced by CUMS. Therefore, the lactobacillus plantarum provided by the invention can be used as a medicament for treating depression.
The application of the animal lactobacillus in preparing the medicament for treating the depression can use the animal lactobacillus as an auxiliary medicament for treating the depression, the animal lactobacillus can relieve depression-like behaviors of depressed rats, improve hippocampal neurons of the depressed rats, improve intestinal flora diversity, recover intestinal flora disorder caused by stress, improve the abundance of enterococcus faecalis, improve the content of intestinal butyric acid and reduce the occurrence risk of inflammatory bowel diseases.
The foregoing description is only illustrative of the preferred embodiment of the present invention, and is not to be construed as limiting the invention, but is to be construed as limiting the invention to any and all simple modifications, equivalent variations and adaptations of the embodiments described above, which are within the scope of the invention, may be made by those skilled in the art without departing from the scope of the invention.
Claims (5)
1. An application of Lactobacillus plantarum in preparing medicament for treating depression is provided.
2. Use of lactobacillus animalis according to claim 1 for the preparation of a medicament for the treatment of depression, wherein said lactobacillus animalis is a bacterial suspension.
3. Use of lactobacillus animalis according to claim 1 for the manufacture of a medicament for the treatment of depression, wherein said lactobacillus animalis can be formulated as a pharmaceutical preparation.
4. Use of lactobacillus animalis according to claim 3 for the manufacture of a medicament for the treatment of depression, wherein the dosage form of the pharmaceutical formulation is selected from at least one of powder, tablet, granule, capsule, solution.
5. Use of lactobacillus animalis according to claim 3 for the manufacture of a medicament for the treatment of depression, wherein the medicament is administered orally.
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