Sodium butyrate alleviates deoxynivalenol-induced hepatic cholesterol metabolic dysfunction via RORγ-mediated histone acetylation modification in weaning piglets

Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic histone acetylation.Therefore,our present study aimed to investigate whether a histone deacetylase inhibitor(sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol(DON) exposure by modulating cholesterol metabolism.Herein,we randomly divided 28 pigs into four groups,which were fed an uncontaminated basal diet,contaminated diet(4 mg DON/kg),uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet(4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.Results:We found that the serum alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP) were all increased in pigs exposed to DON,indicative of significant liver injury.Furthermore,the cholesterol content in the serum of DON-exposed pigs was significantly reduced,compared to the healthy Vehicle group.Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure.In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated.Importantly,NaBu effectively restored parameters associated with liver injury,along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway.Mechanistically,we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment.We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu,as determined by ChIP-qPCR analysis.Notably,nuclear receptor RORγ,a novel regulator of cholesterol biosynthesis,was found in the hyperacetylated regions.Again,a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu.Consistent with RORγ expression,NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR,SQLE,and DHCR24.Furthermore,we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes.Conclusions:Collectively,our results demonstrate the utility of the natural product Na Bu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.

Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression

Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016.

Sodium Butyrate Induces Apoptosis of Human Colon Cancer Cells by Modulating ERK and Sphingosine Kinase 2

Objective To investigate the role of extracellular signal-regulated kinase （ERK） in apoptosis of human colon cancer （HCT116） cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor （U0126） or specific siRNA and exposed to 10 mmol/L sodium butyrate （NaBT） for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. Results The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the UO126-blocked export of SphK2. Conclusion ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.

Supplementation with sodium butyrate improves growth and antioxidant function in dairy calves before weaning

Background: There is increasing research interest in using short-chain fatty acids(SCFAs) including butyrate as potential alternatives to antibiotic growth promoters in animal production. This study was conducted to evaluate the effects of supplementation of sodium butyrate(SB) in liquid feeds(milk, milk replacer, and the mixture of both)on the growth performance, rumen fermentation, and serum antioxidant capacity and immunoglobins in dairy calves before weaning. Forty healthy female Holstein calves(4-day-old, 40 ± 5 kg of body weight) were housed in individual hutches and randomly allocated to 1 of 4 treatment groups(n = 10 per group) using the RAND function in Excel. The control group was fed no SB(SB0), while the other three groups were supplemented with 15(SB15),30(SB30), or 45(SB45) g/d of SB mixed into liquid feeds offered. The calves were initially fed milk only(days 2 to 20), then a mixture of milk and milk replacer(days 21 to 23), and finally milk replacer only(days 24 to 60).Results: The SB supplementation enhanced growth and improved feed conversion into body weight gain compared with the SB0 group, and the average daily gain increased quadratically with increasing SB supplementation. No significant effect on rumen pH;concentrations of NH_3-N, individual and total VFAs;or acetate:propionate(A:P) ratio was found during the whole experimental period. Serum glutathione peroxidase activity increased linearly with the increased SB supplementation, while the serum concentration of maleic dialdehyde linearly decreased. Serum concentrations of immunoglobulin A, immunoglobulin G, or immunoglobulin M were not affected by the SB supplementation during the whole experimental period.Conclusions: Under the conditions of this study, SB supplementation improved growth performance and antioxidant function in pre-weaned dairy calves. We recommended 45 g/d as the optimal level of SB supplementation mixed into liquid feeds(milk or milk replacer) to improve the growth and antioxidant function of dairy calves before weaning.

Sodium butyrate protects against toxin-induced acute liver failure in rats

BACKGROUND: Acute liver failure(ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.METHODS: All rats were randomly divided into control,model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+D- galactosamine+lipopolysaccharide. After induction of ALF,the rats in the treatment group received sodium butyrate(500mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1(HMGB1), liver function parameters, tumor necrosis factoralpha(TNF-α) and interferon-gamma(IFN-γ) were measured.The expression of HMGB1 and nuclear factor-kappa B(NF-κB)p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1,TNF-α and IFN-γ were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group(P<0.05).Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-кB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF(P<0.05).CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.

The expression of glucose regulated protein-94 in colorectal carcinoma cells treated by sodium butyrate

The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.

Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier

AIM To investigate whether gut microbiota metabolite sodium butyrate(Na B)is an effective substance for attenuating non-alcoholic fatty liver disease(NAFLD)and the internal mechanisms.METHODS Male C57BL/6J mice were divided into three groups,normal control were fed standard chow and model group were fed a high-fat diet(HFD)for 16 wk,the intervention group were fed HFD for 16 wk and treated with Na B for 8 wk.Gut microbiota from each group were detected at baseline and at 16 wk,liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1(ZO-1)were detected by immunohistochemistry and realtime-PCR,further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR.RESULTS Na B corrected the HFD-induced gut microbiota imbalance in mice,while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae,Blautia and Lactobacil us.These bacteria can produce butyric acid in what seems like a virtuous circle.And butyrate restored HFD induced intestinal mucosa damage,increased the expression of ZO-1 in small intestine,further decreased the levels of gut endotoxin in serum and liver compared with HF group.Endotoxin-associated genes such as TLR4 and Myd88,pro-inflammation genes such as MCP-1,TNF-α,IL-1,IL-2,IL-6 and IFN-γin liver or epididymal fat were obviously downregulated after Na B intervention.Liver inflammation and fat accumulation were ameliorated,the levels of TG and cholesterol in liver were decreased after Na B intervention,NAS score was significantly decreased,metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group.CONCLUSION Na B may restore the dysbiosis of gut microbiota to attenuate steatohepatitis,which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.

Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2αsignaling pathway in IPEC-J2 cells

Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the protective mechanisms of intestinal damage caused by RV are poorly defined,especially the molecular pathways related to enterocytes apoptosis.Thus,the aim of this study was to investigate the protective effect and mechanism of sodium butyrate(SB)on RV-induced apoptosis of IPEC-J2 cells.Results:The RV infection led to significant cell apoptosis,increased the expression levels of ER stress(ERS)markers,phosphorylated protein kinase-like ER kinase(PERK),eukaryotic initiation factor 2 alpha(eIF2α),caspase9,and caspase3.Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis.The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78(GRP78),PERK,and eIF2α.In addition,SB treatment restrained the ERS-mediated apoptotic pathway,as indicated by downregulation of C/EBP homologous protein(CHOP)mRNA level,as well as decreased cleaved caspase9 and caspase3 protein levels.Furthermore,siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis.Conclusions:These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2αsignaling pathway via GPR109a,which provide new ideas for the prevention and control of RV.

Effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823

瞄准：在增长和人的胃的腺癌房间线 BGC-823 的基因表示上调查 tachyplesin 和 n 钠丁酸盐的效果。方法：BGC-823 房间的增长上的 tachyplesin 和 n 钠丁酸盐的效果与尝试平底锅蓝色染料排除测试被决定并且他染色。房间周期上的 tachyplesin 和 n 钠丁酸盐的效果被流动血细胞计数检测。c-erbB-2， c-myc， p53 和 p16 的蛋白质层次被免疫细胞化学检验。结果：禁止的效果在 2.0 mg/L tachyplesin 和 2.0 mmol/L n 钠丁酸盐处理以后是类似的，细胞的生长的禁止的率分别地是 62.66% 和 60.19% ，并且各自的最大的有丝分裂的索引被 49.35% 和 51.69% 分别地减少。Tachyplesin 和 n 钠丁酸盐处理能显著地在 /G (1 ) 分阶段执行并且减少的 G (0 ) 增加房间的比例在 S 的比例阶段。当表示肿瘤铺平时， oncogene c-erbB-2， c-myc，和 mtp53 蛋白质的表示层次是下面调整的压制或基因 p16 蛋白质在有 tachyplesin 或 n 钠丁酸盐的处理以后是起来调整的。在有 1.0 mmol/L n 钠丁酸盐的联合的 1.0 mg/L tachyplesin 的效果比他们在改变房间周期分发和 c-erbB-2， c-myc， mtp53 和 p16 蛋白质的表示的单个处理显然优异。在联合处理以后的 BGC-823 房间的细胞的生长的禁止的率是 62.29% ，最大的有丝分裂的索引被 51.95% 减少。结论：肿瘤房间的区别 inducer 在肿瘤房间， oncogene 和肿瘤压制的关联词的表示或基因的增长上作为 n 钠丁酸盐有类似的效果的 Tachyplesin。它也在肿瘤房间的区别上有协同的效果。

Effect and Comparison of Sodium Butyrate and Trichostatin A on the Proliferation/Differentiation of K562

In order to explore the molecular mechanisms of sodium butyrate and trichostatin A on K562 cell proliferation/differentiation, K562 cells were grown in the absence or presence of sodium butyrate or trichostatin A The percentage of viable cells was determined by trypan blue exclusion Differentiation was determined by nitro-blue tetrazolium (NBT) reduction and cell surface adhesion molecules analyzed by FACS Cell cycle distribution was studied after DNA staining by propidium iodide Cell cycle regulatory proteins were detected by Western blot and reverse transcription-polymerase chain reaction The results showed that sodiun butyrate blocked cells mainly at the G0/G1 phase of the cell cycle, whereas trichostatin A arrested the cells at G2 phase Sodium butyrate could down-regulate the mRNA expression of cyclin D1, but not affect its protein expression; down-regulate the protein expression of cyclin D3, but not affect its mRNA expression Trichostatin A showed similar effects on cyclin D1 and D3 as sodium butyrate Both sodium butyrate and trichostatin A could stimulate p21 expression of K562 cells at mRNA and protein levels It may be concluded that sodium butyrate and trichostatin A could promote the proliferation/differentiation of the K562 cells, which might be contributed to the induced expression of cyclin D3 and p21 proteins

The Effect of Sodium Butyrate in Combination with ATRA on the Proliferation/Differentiation of SKM-1

To explore the molecular mechanisms of sodium butyrate working on SKM-1 cell proliferation/differentiation and to study its synergistic effect with all-trans retinoic acid (ATRA), SKM-1 cells were grown in the absence or presence of sodium butyrate and/or ATRA. The percentage of viable cells was determined by trypan blue exclusion. Differentiation was determined by nitroblue tetrazolium (NBT) reduction and cell surface adhesion molecules was analyzed by FACS. Cell cycle distribution was examined after DNA staining by propidium iodide. D-type cyclins, cdks and P21 mRNA were studied by reverse transcription-polymerase chain reaction. Our results showed that sodiun butyrate and/or ATRA blocked cells mainly in the G 0/G 1 phase of the cell cycle. ATRA inhibited the mRNA expression of CDK6, CDK4, cyclinD3 and cyclinD1. Sodium butyrate inhibited the mRNA expression of CDK2, cyclinD2 and cyclinD1. ATRA and sodium butyrate inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclinD1, cyclinD2 and cyclinD3. Both ATRA and/or sodium butyrate stimulated p21 expression at the mRNA levels. Our results suggest that the effect of sodium butyrate on cell proliferation/differentiation might be linked to its ability to induce expression of p21 mRNA and inhibit the cyclin-cdk complexes. Our observations support the notion that the sodium butyrate works synergistically with ATRA.

A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon

AIM: To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon. METHODS: One-gram sodium butyrate coated tablets containing 13C-butyrate were orally administered to 12 healthy subjects and 12 Crohn's disease patients and the rate of 13C-butyrate absorption was evaluated by 13CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid (500 mg) was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration. RESULTS: The coated formulation delayed the 13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn's disease patients than in healthy subjects. The variability of the peak 13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time. CONCLUSION: Simultaneous evaluation of breath 13CO2 and tauroursodeoxycholic acid concentration- time curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn's disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.

Possible mechanism for the regulation of glucose on proliferation, inhibition and apoptosis of colon cancer cells induced by sodium butyrate

AIM: To study the effect of glucose on sodium butyrate- induced proliferation inhibition and apoptosis in HT-29 cell line, and explored its possible mechanisms. METHODS: HT-29 cells were grown in RPMI-1640 medium supplemented with 10% fetal calf serum, and were allowed to adhere for 24 h, and then replaced with experimental medium. Cell survival rates were detected by MTT assay. Apoptosis was detected by TUNEL assay. Glucose transport protein 1 (GLUT1) and monocarboxylate transporter 1 (MCT1) mRNA expression was detected by RT-PCR. RESULTS: Low concentration of glucose induced apoptosis and regulated proliferation in HT-29 cell line, and glucose can obviously inhibit the effect of proliferation inhibition and apoptosis induced by sodium butyrate. Glucose also down-regulated the expression of MCT1mRNA (0.28 ± 0.07 vs 0.19 ± 0.10, P < 0.05), and decreased the expression of GLUT1mRNA slightly (0.18 ± 0.04 vs 0.13 ± 0.03, P < 0.05). CONCLUSION: Glucose can regulate the effect of proliferation inhibition and apoptosis induced by sodium butyrate and this influence may be associated with the intracellular concentration of glucose and sodium butyrate.

Inhibition of mouse B16 melanoma by Sodium butyrate correlated to tumor associated macrophages differentiation suppression

Objective: As one member of the histone deacetylase inhibitor (HDACi) family, Sodium butyrate (NaB) was found out that could be used as a differentiation inducer of much cancer cell. But its effects on tumor microenvironment cells are not well recognized. The goal of this research is to investigate the effect of NaB on B16 melanoma and analysis its relevant mechanism. Methods: We observed the effect of sodium butyrate on B16 melanoma in vivo and in vitro. MTT method was performed to detect cell apoptosis rate after treatment. Tumor associated macrophage infiltration condition was detected by flow cytometry. Western-blotting and immunohistochemical method were used to detect the expression of tumor associated macrophage cytokines. Results: A certain concentration of sodium butyrate could effectively inhibit B16 melanoma growth in vivo and in vitro. Compared with the control group (45.00 ± 3.43%), macrophage differentiation in the 1.0g / kg group (37.54 ± 2.34%), 2.0g / kg group (41.62 ± 3.10%) and 3.0g / kg group (29.28 ± 4.42%) group were all inhibited to varying degrees. The inhibitory effect was most significant in the 5.0 g / kg group (19.92 ± 4.80%), and the difference was statistically significant (P <0.01).At the same time we observed the relevant macrophage factors were down-regulated compared to the control. Conclusion: Sodium butyrate could effectively inhibit B16 melanoma growth through suppressing tumor associated macrophage proliferation and reduce relevant pro-tumor macrophage factors expression, which may help to promote the clinical study of melanoma epigenetic therapy.

MODULATION OF MDR-1 GENE IN HUMAN BREAST CANCER CELLS BY SODIUM BUTYRATE AND DMSO

Objective: To analyze the regulation effect of MDR-1 gene in human breast cancer cell by the differentiating agents, sodium butyrate and dimethyl sulfoxide. Methods: 1. A sensitive assay, RT-PCR, was used to measure the mRNA level before and after the treatment of sodium butyrate, DMSO, using β-actin as control; 2. Evaluated the effect of sodium butyrate, DMSO on MDR-1 gene expression of human breast cancer at the protein level by immunoflow cytometry; 3. P-glycoprotein function was examined after accumulation of the fluorescent drug, Phodamine-123, by flow cytometry; 4. Chemosensitivity to doxorubicin was analyzed using the MTT assay. Results: Sodium butyrate and DMSO were found to increase the MDR characteristics on MDR-1 gene, MDR-1 expression levels, P-glycoprotein function and chemosensitivity to doxorubicin. Conclusion: sodium butyrate, DMSO can modulate the MDR-1 gene at gene level, protein level, protein function level and cell level.

Contribution of Decreased Expression of Ku70 to Enhanced Radiosensitivity by Sodium Butyrate in Glioblastoma Cell Line(U251)

The present study investigated the enhanced radiosensitivity of U-251 cells induced by sodium butyrate（NaB） and its possible mechanisms.Increased radiosensitivity of U251 cells was examined by clonogenic cell survival assays.The expression of Ku70 mRNA and protein was detected by using RT-PCR and Western blotting respectively.γ-H2AX foci were measured at different time points after ionizing irradiation alone or combined with NaB treatment.The results showed that cell survival rate was significantly reduced,both D0 and Dq values were decreased（D0：1.43 Gy vs.1.76 Gy;Dq：1.22 Gy vs.2.05 Gy） after the combined treatment as compared with irradiation alone,and sensitivity enhancing ratio（SER） reached 1.23.The average number of γ-H2AX foci per cell receiving the combined treatment was significantly increased at different time points,and the expression levels of Ku70 mRNA and protein were suppressed by NaB in a dose-dependent manner.It was concluded that enhanced radiosensitivity induced by NaB involves an inhibited expression of Ku70 and an increase in γ-H2AX foci,which suggests decreased ability in DSB repair.

Effects of Nano-sustained Release Sodium Butyrate on Growth and Intestinal Cell Proliferation of Grass Carps

Taking grass carps with the initial weight of about 20g as the research object,the basic feeds of grass carps were added with0.0%,0.1%,0.3%,0.6%,0.8%,and 1% of nano-sustained release sodium butyrate to prepare 6 types of experimental feeds with equal nitrogen and energy.The effects of different concentrations of nano-sustained release sodium butyrate were surveyed on growth and intestinal cell proliferation of grass carps.The experiment was carried out in cages with 50 carps per cage,and each treatment was repeated 3 times for60 days.Experimental results indicated that the addition of nano-sustained release sodium butyrate significantly promoted the growth of grass carps and significantly increased the ratio of intestinal villus to crypt depth.When the addition of nano-sustained release sodium butyrate was0.6%,the weight increase rate,specific growth rate,fullness and intestinal villus height of grass carps were the highest,which was significantly higher than that of the control group(P < 0.05).The study results indicated that addition of appropriate amount of nano-sustained release sodium butyrate can promote the growth of grass carps through increasing the intestinal villus height,and the suitable addition dosage was0.6%.