Zinc-rich probiotic preparation and application thereof

Abstract

The invention discloses a zinc-rich probiotic preparation and application thereof. The probiotic agent provided by the invention comprises a Bifidobacterium longum subsp. Longum CCFM1195 strain and a Lactobacillus paracasei CCFM1069 strain, and can improve food intake and food utilization rate, increase body weight, promote growth, increase serum zinc and excrement zinc content, improve ALP activity, significantly up-regulate serum GH level, down-regulate small intestine zinc ion transporter protein ZIP4 gene expression level, reduce small intestine zinc ion transporter protein ZIP4 gene expression level, reduce small intestine zinc ion transporter protein ZIP4 gene expression level, reduce small intestine zinc ion transporter protein ZIP4 gene expression level, reduce small intestine zinc ion transporter protein ZIP4 gene expression level, and improve food quality. The gene expression of ZnT2 is up-regulated, and the zinc homeostasis in cells is regulated and controlled. The probiotic agent disclosed by the invention can be used for preparing products (such as foods, medicines or health-care foods) for promoting the growth of children, and has a huge application prospect.

Description

Technical Field

[0001] The invention belongs to the field of biotechnology, and in particular relates to a zinc-rich probiotic preparation and application thereof. Background Art

[0002] Zinc is a trace element necessary for maintaining normal growth and development and normal physiological functions of the human body. It is mainly involved in the composition of proteins and nucleic acids in the body. It maintains protein structure and function by coordinating with zinc finger and ring finger protein domains, and plays a key role in cell processes such as differentiation, apoptosis, and proliferation. Zinc cannot be synthesized in the body and can only be provided by external food. Zinc deficiency can cause growth and development disorders in children, metabolic disorders, reduced immunity, gastrointestinal diseases, loss of appetite, etc. It can damage the specific and non-specific immune systems, leading to increased susceptibility to bacterial, viral and fungal pathogens. Long-term zinc deficiency can cause irreversible damage to the body's growth and reproductive system, and in severe cases it can also affect intellectual development.

[0003] Probiotics are a general term for active microorganisms that are beneficial to the host. When the body ingests a sufficient amount of probiotics, it can promote the health of the body. Different probiotics have different effects. The effect of using multiple probiotics together is better than that of a single strain. Bifidobacterium and Lactobacillus are two important types of probiotics that can be added to food. Therefore, probiotic compound preparations composed of bifidobacteria and lactobacillus have become a research hotspot in the field of functional foods. Some active strains such as bifidobacteria and lactobacillus that are beneficial to the health of the host contain carboxylic acid proteins on their surface proteins, which can be used as organic carriers of trace elements to enrich and transform metal ions and promote the binding of lactobacilli with Zn 2+ The combination of zinc and lactic acid can also degrade oxalate in the intestine, promote the health of intestinal mucosa, improve intestinal permeability barrier, and promote zinc absorption. Based on previous research, we obtained a patented bacterium (CN115197865A) with strong zinc-enriching ability-zinc-enriching Bifidobacterium longum subspecies CCFM1195. As a new dietary zinc source containing active lactic acid bacteria, it not only has the probiotic function of lactic acid bacteria, but also can supplement zinc to meet the body's nutritional needs. The patented bacterium (CN111117907A) Lactobacillus paracasei CCFM1069 can tolerate the human gastrointestinal environment, significantly increase the water content of feces, increase the propulsion rate of the small intestine, and increase the content of short-chain fatty acids in the intestine, and has a very broad application prospect.

[0004] Currently, zinc gluconate is used as a zinc supplement for the treatment of malnutrition, anorexia, growth retardation, skin acne and other diseases, and has achieved good results. However, the side effects caused by large intake, such as nausea and vomiting, defecation difficulties, skin itching, dizziness, diarrhea, etc., cannot be ignored. Therefore, exploring zinc supplements with high absorption conversion rates and low side effects is an urgent problem to be solved. Summary of the invention

[0005] In order to solve the above problems, the purpose of the present invention is to provide a zinc-rich probiotic preparation and application.

[0006] One of the technical solutions adopted by the present invention to solve the technical problem is: providing a zinc-rich probiotic preparation, the zinc-rich probiotic preparation comprising Bifidobacterium longum subsp. longum CCFM1195 strain with a preservation number of GDMCC No: 61958 and Lactobacillus paracasei CCFM1069 strain with a preservation number of GDMCC No: 60719, and the ratio of the number of live bacteria of the CCFM1195 strain to that of the CCFM1069 strain is 4:1.

[0007] The term "probiotics" refers to a class of active microorganisms that are beneficial to the host by colonizing in the human body and changing the composition of the flora in a certain part of the host. By regulating the host mucosal and systemic immune function or by regulating the balance of intestinal flora, it promotes nutrient absorption and maintains intestinal health, thereby producing single microorganisms or mixed microorganisms with clear composition that are beneficial to health. The beneficial bacteria or fungi in the human body and animals mainly include yeast, probiotic spore bacteria, Clostridium butyricum, Lactobacillus, Bifidobacterium, Actinomycetes, Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus crispatus, Lactobacillus delbrueckii subspecies bulgaricus, Lactobacillus fermentum, Lactobacillus salivarius, Lactobacillus gasseri, Lactobacillus reuteri, Lactobacillus rhamnosus, etc.

[0008] Bifidobacterium longum subsp. longum CCFM1195 was deposited in Guangdong Microbiological Culture Collection Center on September 28, 2021, with a deposit number of GDMCC No: 61958, and the deposit address is 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, and is recorded in the Chinese invention patent application with publication number CN115197865A. Lactobacillus paracasei CCFM1069 was deposited in Guangdong Microbiological Culture Collection Center on July 10, 2019, with a deposit number of GDMCC No: 60719, and the deposit address is 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, and is recorded in the Chinese invention patent application with publication number CN111117907A.

[0009] Preferably, in the probiotic, the total number of viable bacteria of CCFM1195 strain and CCFM1069 strain is not less than 10 9 CFU / mL or 10 9 CFU / g.

[0010] Preferably, the dosage form of the probiotic includes lyophilized powder, capsule, tablet or granule.

[0011] Preferably, the probiotic is a freeze-dried powder and further comprises galacto-oligosaccharide, inulin, strawberry powder, hawthorn powder, isomaltooligosaccharide, hawthorn concentrated powder, and complex vitamins and minerals.

[0012] Preferably, the probiotic comprises, by weight: 47.2 parts of galacto-oligosaccharides, 25 parts of inulin, 7.5 parts of strawberry powder, 7.5 parts of composite bacterial powder of Bifidobacterium longum subspecies longum CCFM1195 strain and Lactobacillus paracasei CCFM1069 strain, 5 parts of hawthorn powder, 5 parts of isomaltooligosaccharides, 2.5 parts of hawthorn concentrated powder, and 0.3 parts of complex vitamins and minerals.

[0013] The second technical solution adopted by the present invention to solve its technical problem is: to provide the use of the above zinc-rich probiotic preparation in the preparation of products promoting children's growth.

[0014] The third technical solution adopted by the present invention to solve the technical problem is: to provide the use of the above zinc-rich probiotic preparation in the preparation of a product having at least one of the following functions:

[0015] (1) Increase food intake and food utilization, increase body weight, and promote growth;

[0016] (2) Increase serum zinc and fecal zinc levels and ALP activity, and significantly increase serum GH levels;

[0017] (3) Down-regulate the gene expression level of the small intestinal zinc ion transporter ZIP4, up-regulate the gene expression of ZnT2, and regulate intracellular zinc homeostasis.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] 1. The zinc-rich probiotic preparation of the present invention can significantly increase food intake and food utilization, increase body weight and promote growth.

[0020] 2. The zinc-rich probiotic preparation of the present invention can significantly increase serum zinc and fecal zinc content and increase ALP activity, and significantly increase serum GH levels.

[0021] 3. The zinc-rich probiotic preparation of the present invention can significantly downregulate the gene expression level of the small intestinal zinc ion transporter ZIP4, upregulate the gene expression of ZnT2, and regulate the intracellular zinc homeostasis.

[0022] At the same time, the zinc-rich probiotic preparation product of the present invention is matched with three kinds of prebiotics (galacto-oligosaccharides, inulin, isomalto-oligosaccharides) and complex vitamins and minerals. Studies have shown that the intake of prebiotics can improve children's environmental intestinal dysfunction (this dysfunction plays a core role in children's growth retardation), galacto-oligosaccharides have functions similar to breast milk oligosaccharides, can improve the digestion and absorption capacity of ileum to carbohydrates, and are conducive to maintaining the barrier function of ileum; inulin has the effect of enhancing the body's immunity, promoting the absorption and synthesis of minerals and vitamins, and maintaining bone health. At the same time, the formula adds calcium, iron, zinc, and vitamins A and D, which are very important for children, among which calcium is an important part of bones and teeth; the main function of iron is to manufacture hemoglobin, myoglobin, cytochrome, participate in the transport of oxygen in the body and tissue respiration and human oxidation, and when it is lacking, the child may show anemia, spoon-shaped fingers, muscle and cognitive function reduction; vitamin A promotes growth, maintains the integrity of mucosal epithelial cells, promotes bone, tooth development and immunity; the main physiological function of vitamin D is to regulate calcium and phosphorus absorption, cell metabolism, and maintain bone homeostasis. The formula improves nutrient absorption and utilization while supplementing the vitamins and minerals needed by children, benefiting children's nutrition and health in all aspects. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The present invention will be further described below in conjunction with embodiments with reference to the accompanying drawings.

[0024] Figure 1 This is a graph showing the daily food intake of rats in each group in Effect Example 1.

[0025] Figure 2 This is a diagram of the food utilization rate of rats in each group in Effect Example 1.

[0026] Figure 3 This is a graph showing the body weight of rats in each group in Effect Example 1. DETAILED DESCRIPTION

[0027] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0028] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0029] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0030] The terms "comprising," "including," "having," "containing," or any other variations thereof, as used in the following examples, are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus comprising the listed elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such composition, step, method, article, or apparatus.

[0031] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0032] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0033] The zinc-deficient feed TP0690-01 (1 ppm) and control feed TP0690C (35 ppm to 38 ppm) involved in the following examples were purchased from Nantong Trophy Feed Technology Co., Ltd.

[0034] The rat growth hormone (GH) ELISA kit involved in the following examples was purchased from Shanghai ELISA Biotechnology Co., Ltd.;

[0035] The RNA extraction kit, reverse transcription kit, and SYBR reagents involved in the following examples were purchased from Nanjing Novozymes Co., Ltd.

[0036] The zinc-rich Bifidobacterium longum subspecies longum CCFM1195 (zinc content 2.82 mg / g) involved in the following embodiments was disclosed in patent document CN115197865A on October 18, 2022, and Lactobacillus paracasei CCFM1069 was disclosed in patent document CN111117907A on May 8, 2020, both of which were provided by Wuxi Institute of Special Food and Nutrition and Health;

[0037] The HNO3 and other conventional reagents or consumables involved in the following examples were purchased from Sinopharm Chemical Reagent Co., Ltd.;

[0038] The PCR primers involved in the following examples were purchased from Shanghai Bioengineering Co., Ltd.

[0039] The following provides the best embodiment of the present invention.

[0040] Example 1

[0041] The preparation method of a probiotic-free crude preparation (auxiliary material) of this embodiment is carried out by the following steps:

[0042] Step 1: Weigh 47.2g galacto-oligosaccharide, 25g inulin, 7.5g strawberry powder, 5 portions of hawthorn powder, 5g isomaltooligosaccharide, 2.5g hawthorn concentrated powder, and 0.3g multivitamin minerals.

[0043] Step 2: Mix the above materials, stir and mix well to obtain a probiotic-free crude preparation (auxiliary material), and store it at 4°C.

[0044] Example 2

[0045] Step 1: Weigh 6 g of zinc-rich Bifidobacterium longum subspecies longum CCFM1195 and 1.5 g of Lactobacillus paracasei CCFM1069, mix and stir evenly to obtain composite bacterial powder.

[0046] Step 2: Mix the above composite bacterial powder with Example 1, stir evenly, and obtain a crude zinc-rich probiotic preparation.

[0047] Effect Example 1: Zinc-rich probiotic preparation significantly increased food intake and food utilization, and increased the body weight of zinc-deficient rats

[0048] Zinc is a necessary trace element for maintaining normal growth and development and normal physiological functions of the human body. Zinc cannot be synthesized in the body and can only be provided by external food. Zinc deficiency can cause growth and development disorders in children, so this experiment uses zinc-deficient feed to model. Specifically, after 48 SD rat pups adapted for one week, they were randomly divided into 8 groups, blank group, model group, and intervention group (4 experimental groups and 2 comparative groups). During the entire experiment, the blank group rats were fed with standard control feed, and the remaining groups of rats were fed with zinc-deficient feed; the blank control group and the model group were gavaged with sterile saline every day throughout the experimental period, and each intervention group was gavaged with the corresponding solution.

[0049] After the experiment, the rats were anesthetized by intraperitoneal injection of 0.35 mL / 100 g (mouse weight) of 10% chloral hydrate, and blood was collected from the vein. The rats were then killed by dislocating the cervical vertebra. The rats were quickly dissected, and the small intestinal tissue of the rats was taken and stored in a -80°C refrigerator for subsequent testing. The blood was centrifuged at 4°C, 3000 g for 10 min, and the supernatant was taken and frozen at -80°C for later use. The experimental process is shown in Table 1.

[0050] Table 1 Test process

[0051]

[0052] During the entire experiment, the food intake, body weight and body length of each group of rats before and after the experiment were measured at the same time every other day, and the food utilization rate of each group of rats was calculated, and inter-group comparison analysis was performed. Food utilization rate = average daily food intake / average daily weight gain × 100%.

[0053] The experimental results are as follows Figure 1-3 As shown by Figure 1 , 2 It can be seen that the daily food intake (7.35±0.12) and food utilization rate (21.06±2.57) of the model group were significantly lower than those of the blank group (18.94±0.34, 52.46±5.98), indicating that the food intake and food utilization rate of the zinc-deficient model rats decreased. Compared with the model group, the food intake of the other experimental groups increased to varying degrees, among which the food intake of the zinc-rich probiotic preparation group of Example 2 (17.64±0.13, 46.87±5.47) increased significantly, indicating that the zinc-rich probiotic preparation can promote the appetite of rats and promote increased food intake. Figure 3 It can be seen that the body weight of rats in the model group (132.5±1.10) was significantly lower than that in the blank group (265.9±13.01). After the intervention of Example 2, the body weight increased significantly (210.8±4.31), indicating that the zinc-rich probiotic preparation of Example 2 can increase the body weight of rats by promoting the appetite of rats and increasing the utilization rate of food.

[0054] Effect Example 2: Zinc-rich probiotic preparations can significantly increase serum zinc, zinc-containing enzymes (ALP) and fecal zinc content

[0055] The experimental process including SD rat grouping, modeling and treatment methods was the same as that in Example 1.

[0056] After the serum was melted on ice, an appropriate amount of serum was taken and the ALP and zinc content in the serum was detected using an automatic biochemical analyzer. 0.1 g to 0.3 g of the freeze-dried fecal samples were weighed and placed in 7 mL of concentrated HNO3 (16 mol / L) for digestion overnight. Digested at 121 ° C for 4 h, diluted to 50 mL with deionized water, and filtered through a 0.22 μm filter to remove insoluble matter. The zinc content in the feces was determined using an inductively coupled plasma mass spectrometer (ICP-MS).

[0057] The synergistic index q = A / (B+CB*C), where A represents the rate of change of the test index in the zinc-rich probiotic product intervention group, B represents the rate of change of the test index in the non-probiotic product intervention group, and C represents the rate of change of the index in the zinc-rich CCFM1195+CCFM1069 group. If q is between 0.85 and 1.15, it is a simple addition; between 1.15 and 20, it is an enhancement; >20 is a significant enhancement; between 0.85 and 0.55, it is antagonism; <0.55 is a significant antagonism.

[0058] Table 2 Effects of individual components and combinations on serum ALP, zinc and fecal zinc content in zinc-deficient rats

[0059]

[0060]

[0061] Note: Different letters between groups indicate significant differences (P < 0.05)

[0062] The experimental results are shown in Table 2. Compared with the blank group, the serum zinc concentration and ALP concentration of the model group rats decreased significantly, indicating that zinc deficiency has a significant negative effect on zinc-related enzymes. Compared with the model group, there was no significant difference in serum zinc concentration and ALP content in the group without probiotic product intervention, and the serum zinc concentration and ALP concentration in the group with zinc-rich probiotic product intervention increased significantly, and the synergistic index q>1.15, indicating that the combination of Example 1 and the composite bacterial powder has a synergistic effect. Zinc is mainly excreted from feces, and the excretion of zinc in urine is almost unaffected by zinc intake. Before the intervention of various zinc supplements, the fecal zinc content of the model group was significantly reduced, indicating that the zinc-deficient diet has caused a sharp decrease in endogenous zinc content in rats. After two weeks of intervention, compared with the model group, Example 1 did not increase the zinc content in rat feces, while the zinc-rich CCFM1195+CCFM1069 group significantly increased the zinc content in rat feces, and the increase rate was higher than that of the control group. In addition, the zinc-rich probiotic preparation of Example 2 after the combination of the two significantly increased the zinc content in feces, and the synergistic index q>1.15, which had a synergistic effect.

[0063] Effect Example 3: Effects of individual components and combination on serum GH content in zinc-deficient rats

[0064] The experimental process including SD rat grouping, modeling and treatment methods was the same as that in Example 1.

[0065] A rat growth hormone (GH) enzyme-linked immunosorbent assay kit was used to determine the GH content in serum according to the instructions in the kit.

[0066] Table 3 Effects of individual components and combinations on serum GH levels in zinc-deficient rats

[0067]

[0068]

[0069] As shown in Table 3, compared with the normal control group, the GH level in the serum of the model group rats decreased significantly, indicating that the zinc-deficient diet has significantly affected the level of growth-related hormones in the serum of rats. Although there was an increase after the intervention of the probiotic product, there was no significant difference. Compared with the model group, the improvement rates of comparison examples 1 and 2 were 39.86% and 38.19%, respectively, which were significantly different from the model group. After the intervention of the zinc-rich probiotic product, the effect was better than that of the non-probiotic product alone, and the improvement rate was higher than that of the zinc-rich CCFM1195+CCFM1069. The combined synergistic index was 1.31, showing the synergistic effect of the two.

[0070] Effect Example 4: Effects of individual components and combinations on gene expression of zinc transporter in the small intestine of zinc-deficient rats The experimental procedures including grouping, modeling and treatment methods of SD rats were the same as those of Effect Example 1.

[0071] After killing the rats, appropriate amounts of small intestinal tissue were taken and total RNA was extracted from the tissue using an RNA extraction kit. cDNA was synthesized according to the requirements of the reverse transcription kit and mixed with fluorescent Mix before fluorescent quantitative PCR analysis. The primer design is shown in Table 4 and the results are shown in Table 5.

[0072] Table 4 Primer design table

[0073]

[0074] Table 5 Expression levels of zinc transporter genes ZIP4 and ZnT2 in the small intestine of zinc-deficient rats

[0075]

[0076]

[0077] ZIP4 is the main transporter protein expressed in the small intestine for absorbing zinc ions in the diet, and is responsible for importing zinc ions from the lumen into intestinal cells. As shown in Table 5, compared with the blank control group, the expression level of ZIP4 gene in the small intestine tissue of rats in the model group was significantly increased, the zinc content in the body was reduced, and the expression of ZIP4 gene was upregulated to transport more zinc ions. After intervention with no probiotic products, the expression level of ZIP4 gene was not significantly different from that in the model group. After intervention with zinc-rich CCFM1195+CCFM1069 and zinc-rich probiotic products, the expression level of ZIP4 gene was significantly downregulated compared with the model group, indicating that both can increase the level of zinc ions in the body.

[0078] As shown in Table 5, the expression level of ZnT2 gene in the small intestinal cells of rats in the model group was significantly reduced. Since ZnT2 is expressed in cells, it is responsible for collecting zinc in lysosomes and endosomes to protect cells from zinc toxicity. The reduction in gene expression level indicates that the intracellular zinc content is reduced. Compared with the model group, zinc-rich CCFM1195+CCFM1069 and zinc-rich probiotic products can significantly upregulate ZnT2 gene expression, indicating that zinc-rich CCFM1195+CCFM1069 and zinc-rich probiotic products can increase intracellular zinc content and promote the growth and development of zinc-deficient rats.

[0079] From the results of the above experimental examples and test examples, it can be seen that the zinc-rich probiotic product can promote rat food intake, increase body weight, increase serum zinc content and ALP activity, increase growth hormone levels, and regulate small intestinal ZnT2 and ZIP4 gene expression to maintain body zinc homeostasis, indicating that the zinc-rich probiotic product can promote the growth and development of zinc-deficient rats. The probiotic agent of the present invention can be used to prepare products (such as food, medicine or health food, etc.) that promote children's growth, and has great application prospects.

[0080] Although the specific implementation modes of the present invention are described above, those skilled in the art should understand that the specific implementation modes described are only illustrative and are not intended to limit the scope of the present invention. Equivalent modifications and changes made by those skilled in the art in accordance with the spirit of the present invention should be included in the scope of protection of the claims of the present invention.

Claims

1. A zinc-rich probiotic preparation, characterized in that: The zinc-rich probiotic preparation comprises Bifidobacterium longum subsp. longum CCFM1195 strain with a preservation number of GDMCC No: 61958 and Lacticaseibacillus paracasei CCFM1069 strain with a preservation number of GDMCC No: 60719, and the ratio of the number of live bacteria of the CCFM1195 strain to that of the CCFM1069 strain is 4:

1.

2. The zinc-rich probiotic preparation according to claim 1, characterized in that In the probiotics, the total number of viable bacteria of CCFM1195 strain and CCFM1069 strain is not less than 10 9 CFU / mL or 10 9 CFU / g.

3. The zinc-rich probiotic preparation according to claim 1, characterized in that The dosage form of the probiotics includes freeze-dried powder, capsules, tablets or granules.

4. The zinc-rich probiotic preparation according to claim 1, characterized in that The probiotic is a freeze-dried powder and also includes galacto-oligosaccharide, inulin, strawberry powder, hawthorn powder, isomaltooligosaccharide, hawthorn concentrated powder, and complex vitamins and minerals.

5. The zinc-rich probiotic preparation according to claim 4, characterized in that: The probiotic comprises, by weight: 47.2 parts of galacto-oligosaccharide, 25 parts of inulin, 7.5 parts of strawberry powder, 7.5 parts of composite bacterial powder of Bifidobacterium longum subspecies longum CCFM1195 strain and Lactobacillus paracasei CCFM1069 strain, 5 parts of hawthorn powder, 5 parts of isomaltooligosaccharide, 2.5 parts of hawthorn concentrated powder, and 0.3 parts of complex vitamins and minerals.

6. Use of the zinc-rich probiotic preparation according to any one of claims 1 to 5 in the preparation of a product that promotes children's growth.

7. Use of the zinc-rich probiotic preparation according to any one of claims 1 to 5 in the preparation of a product having at least one of the following functions: (1) Increase food intake and food utilization, increase body weight, and promote growth; (2) Increase serum zinc and fecal zinc levels and ALP activity, and significantly increase serum GH levels; (3) Down-regulate the gene expression level of the small intestinal zinc ion transporter ZIP4, up-regulate the gene expression of ZnT2, and regulate intracellular zinc homeostasis.

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