JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Sijia Wu,Ping Jiang,Xiaoliang Zhang,Chen Mao,Yaxi Dai,Hong Zhuang,Yong Pang
Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10–7 and (6.63 ± 2.31) × 10–7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.
研究领域:
药理学
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生物物理学
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细胞生物学
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膜科学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 29
·期 5
·1-14
·
IF 3.4
Xinya Yu,Xiaoxi Li,Yunchun Xu,Yuwei Li,Ye Zhou,Junhua Zhang,Le Guo
Ulcerative colitis (UC) is a chronic idiopathic inflammatory condition affecting the rectum and colon. Inflammation and compromisation of the intestinal mucosal barrier are key in UC pathogenesis. Resveratrol (Res) is a naturally occurring polyphenol that exhibits anti‑inflammatory and antioxidant properties. Nuclear factor erythroid‑2‑related factor 2/heme oxygenase 1 (Nrf2/HO‑1) pathway regulates occurrence and development of numerous types of diseases through anti‑inflammatory and antioxidant activity. However, it is not clear whether Nrf2/HO‑1 pathway is involved in the treatment of Res in UC. Therefore, the present study aimed to investigate whether Res modulates the Nrf2/HO‑1 signaling pathway to attenuate UC in mice. Dextran sulfate sodium (DSS) was used to induce experimental UC in male C57BL/6J mice. Disease activity index (DAI) and hematoxylin eosin (H&E) staning was used to assessed the magnitude of colonic lesions in UC mice. ELISA) was utilized to quantify inflammatory cytokines (IL‑6, IL‑1β, TNF‑α and IL‑10) in serum and colon tissues. Immunohistochemistry and Western blot were used to evaluate the expression levels of tight junction (TJ) proteins [zonula occludens (ZO)‑1 and Occludin] in colon tissues. Pharmacokinetic (PK) parameters of Res were derived from TCMSP database. Networkpharmacology was employed to identify the biological function and pharmacological mechanism of Res in the process of relieving UC, and the key target was screened. The binding ability of Res and key target was verified by molecular docking. Finally, the effectiveness of key target was substantiated by Western blot. Res decreased DAI, ameliorated histopathological changes such as crypt loss, disappeatance of the mucosal epithelium, and inflammatory infiltration in mice. Additionally, Res decreased expression of pro‑inflammatory cytokines IL‑6, IL‑1β and TNF‑α and increased anti‑inflammatory factor IL‑10 expression. Res also restored the decreased protein expression of ZO‑1 and occludin after DSS treatment, increasing the integrity of the intestinal mucosal barrier. The PK properties of Res suggested that Res possesses the therapeutic potential for oral administration. Network pharmacology revealed that Res alleviated UC through anti‑inflammatory and antioxidant pathways, and confirmed that Nrf2 has a high binding affinity with Res and is a key target of Res against UC. Western blotting demonstrated that Res treatment increased the protein levels of Nrf2 and HO‑1. In conclusion, Res treatment activated the Nrf2/HO‑1 pathway to decrease clinical symptoms, inflammatory responses, and intestinal mucosal barrier damage in experimental UC mice.
研究领域:
药理学
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炎症性肠病
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分子生物学
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动物模型
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Xiaoming Luo,Haixing Song,Jing Yang,Bin Han,Ye Feng,Yanbing Leng,Zhaoqiong Chen
Escherichia coli strain Nissle 1917 (EcN) has been widely shown to effectively treat inflammatory bowel diseases (IBDs). Unfortunately, after oral administration, EcN viability dramatically decreases due to severe environmental factors, including low gastric pH, temperature and osmotic pressure. To address these challenges and improve oral bio-availability, this study utilized layer-by-layer assembly (LbL) and ionic cross-linking with CaCl 2 as a method of EcN encapsulation (GEcN). Upon examination, GEcN cells were shown to maintain their ability to grow and proliferate, but had a slightly longer stationary phase (10 h) relative to free EcN (4 h). When exposed to simulated gastric fluid (SGF), a higher number of GEcN cells survived up to 12 h when compared to the other groups. To assess the therapeutic effect of EcN encapsulation in vivo , a TNBS-induced colitis rat model was established. When compared with the oral administration of free EcN, GEcN exhibited a significantly enhanced anti-inflammatory effect. Furthermore, GEcN treatment showed a lower disease activity index (DAI), decreased pro-inflammatory cytokine expression (MPO, TNF-α, IL-6) and increased anti-inflammatory cytokine expression (IL-10). Additionally, rats that received GEcN had much higher ZO-1 expression levels. These results suggest that EcN encapsulation in a chitosan―alginate matrix when utilizing the LbL assembly with CaCl 2 cross-linking can improve probiotic viability in a gastric environmental and thereby offer a more effective treatment for IBDs.
研究领域:
药学
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生物技术
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 9
·4392-4405
·
IF 6.1
Chi Zhang,Yujia Hu,Yi Yuan,Jingke Guo,Henian Li,Qiaoling Li,Shutao Liu
Oxidative stress is generally considered inseparable from the development and exacerbation of ulcerative colitis (UC). Therefore, reducing oxidative stress has become a possible way to alleviate UC. In this study, the therapeutic effects of different doses of liposome-embedded superoxide dismutase (L-SOD) on mice with DSS-induced UC were systematically investigated. The results showed that L-SOD significantly attenuated the signs of colitis in mice, including colonic shortening, diarrhoea, bloody stools, and histopathological changes. L-SOD ameliorated DSS-induced oxidative damage, increased SOD, catalase (CAT), and glutathione (GSH) activities, and decreased malondialdehyde (MDA) levels. In addition, L-SOD ameliorated the inflammatory response by inhibiting the expression of myeloperoxidase (MPO) and pro-inflammatory cytokines and protected barrier function by promoting the expression of the tight junction proteins occludin and ZO-1 in the colon. Importantly, the results demonstrated a bell-shaped distribution of therapeutic effects relative to the administered dose, with an optimal dose of 150 000 U kg−1. These results indicate that L-SOD has great potential as an ingredient in functional foods for the prevention and mitigation of UC.
研究领域:
药理学
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免疫学
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胃肠病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Bochen Song,Peng Li,Shaojia Yan,Yan Liu,Mingkun Gao,Huiyuan Lv,Zengpeng Lv,Yuming Guo
This study aimed to investigate the effects of dietary astragalus polysaccharide (APS) supplementation on the immune function, gut microbiota and metabolism of broiler chickens challenged with necrotic enteritis (NE). Two hundred forty Arbor Acres broiler chicks (one day old) were randomly assigned using a 2 × 2 factorial arrangement into two groups fed different levels of dietary APS (0 or 200 ppm of diet) and two disease challenge groups (control or NE challenged). The results showed that NE infection significantly increased FCR, mortality rate, Th17/Treg (Th17 cells% in blood and ileum, Th17/Treg, IL-17 and IL-17/IL-10 in blood), NO, lysozyme activity and IL-1β in blood, intestinal immune cell proportion and activity (Tc%, Treg% and monocyte phagocytic activity in ileum), intestinal inflammatory cytokines (TLR2, NF-κB, TNF-α and IL- 6) gene expression levels, and the number of Clostridium perfringens in cecum. NE infection significantly reduced body weight gain, thymus index, lymphocyte proliferation activity in blood and ileum, villus height and V/C in jejunum, Th cells% and Mucin2 gene expression in ileum. Dietary APS supplementation significantly increased body weight, feed intake, proportion of immune cells (T cells in blood and Tc, Treg in ileum), lymphocyte proliferation activity, V/C in jejunum, and ZO-1 gene expression in ileum. Dietary APS supplementation significantly reduced FCR and mortality rate, Th17/Treg, Th17%, intestinal pathology scores, intestinal inflammatory cytokine gene expression levels, and the number of Clostridium perfringens in cecum. In addition, broilers challenged with NE significantly increased Staphylococcus and Turicibacte r and reduced α diversity of microbiota in ileum. Dietary APS supplementation significantly increased α diversity, Romboutsia , Halomonas , propionic acid, butyric acid, formononetin, taurine, cholic acid and equol and downregulated uric acid, L-arginine and serotonin in ileum. Spearman’s correlation analysis revealed that Romboutsia, Turicibacter, Staphylocpccus, Halomonas, Streptococcus, Escherichia-Shigella, Prevotella , uric acid, L-arginine, jerivne, sodium cholate and cholic acid were related to inflammation and Th17/Treg balance. In conclusion, APS alleviated intestinal inflammation in broilers challenged with NE probably by regulating intestinal immune, Th17/Treg balance, as well as intestinal microbiota and metabolites.
研究领域:
动物科学
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免疫学
·
微生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2022
·
IF 4.114
Hongzeng Li,Wen Yuan,Yuxin Tian,Feiyue Tian,Yunfei Wang,Xiangrong Sun,Yanling Gong
Eugenol, an active ingredient of many medicinal aromatic plants, has been proved to have the hypolipidemic effect, but its potential mechanism of action is still unknown. This study aimed to investigate whether eugenol regulates liver lipid accumulation in high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) rats via the gut-brain-liver axis involving glucagon-like peptide-1 (GLP-1). Hepatic vagotomy was performed in NAFLD rats to determine the role of eugenol in regulating hepatic lipid accumulation via vagus nerve. The results showed that after eight weeks of eugenol administration in NAFLD rats, serum total cholesterol (TC), triglyceride (TG) and hepatic TG decreased. However, eugenol showed no significant effect on the increased food intakes and weight gain caused by the HFD. Eugenol promoted the secretion of GLP-1 into the blood, increased GLP-1 receptor (GLP-1R) expression in the duodenum , liver, arcuate nucleus (ARC) and paraventricular nucleus (PVN), increased c-fos expression in the nucleus tractus solitarii (NTS), and promoted ZO-1 and occludin expression in duodenum. Furthermore, steatosis and lipid accumulation were significantly alleviated. Hepatic vagotomy partially attenuated the improvement of eugenol in hepatic lipid accumulation in NAFLD rats. In conclusion, eugenol regulates hepatic lipid metabolism via a gut-brain-liver axis involving in GLP-1, providing a new strategy for the treatment of NAFLD.
研究领域:
药理学
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肝病学
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内分泌学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2025
·
IF 4.4
Chen Fengming,Wu Shu,Wang Xiaoyu,Li Yinghui,He Binsheng,Fu Yafen,Huang Xingguo,Chen Jiayi
Reducing the negative impact of oxidative stress (OS) on weaned piglets is crucial for the further development of the pig industry. Our previous studies found that Lactobacillus delbrueckii (LAB) can alleviate OS and protect intestinal health by activating TLR2 and TLR4 expressions in weaned piglets. This research aimed to verify whether LAB can alleviate OS and intestinal barrier injuries in IPEC-J2 cells by activating TLR2 and TLR4. IPEC-J2 cells were first pretreated with 10 10 CFU/mL LAB for 12 h, and then were induced to OS by 0.8 mmol/L H 2 O 2 for another 12 h. The results showed that LAB significantly alleviated OS induced by H 2 O 2 , indicated by the downregulation of MDA ( P < 0.05), along with upregulation of GSH-Px, CAT, T-SOD, and T-AOC ( P < 0.05). Besides, LAB significantly alleviated intestinal barrier injuries induced by H 2 O 2 , indicated by the upregulation of Claudin-1, Occludin, and ZO-1 expressions. Subsequently, the IPEC-J2 cells were pretreated with inhibitors of TLR2 (TLR2-IN-C29) and TLR4 (MD2-TLR4-IN-1) in the absence of LAB for 12 h, and then treated with 0.8 mmol/L H 2 O 2 for another 12 h. The results showed that both inhibitors significantly prevented the protection effects of LAB on H 2 O 2 -induced OS, indicated by the downregulation of CAT, SOD1, HO-1, and GSH-Px1 expressions ( P < 0.05). Taken together, LAB treatment can alleviate OS and intestinal injuries induced by H 2 O 2 by activating TLR2 and TLR4 expressions in IPEC-J2 cells, thus providing novel theoretical support for LAB in the prevention and treatment of oxidative damage.
研究领域:
动物科学
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微生物学
·
细胞生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 22
·11676-11689
·
IF 6.317
Abel Wend-Soo Zongo,Daniel Zogona,Mahmoud Youssef,Shuxin Ye,Fuchao Zhan,Jing Li,Bin Li
The intestinal barrier dysfunction associated with chronic inflammation is a major health concern. This work aimed to investigate the protective effect and molecular mechanism of Senegalia macrostachya seed polysaccharide fraction (SMSP2) on inflammation-induced barrier dysfunction using Caco-2 cells and RAW264.7 macrophage co-culture model. The results showed that LPS stimulation of the basolateral RAW264.7 compromised the integrity of the apical differentiated Caco-2 cells monolayer, resulting in decreased transepithelial electrical resistance (TER) and increased inflammatory markers. SMSP2 apical treatment maintained a higher TER value and reduced the epithelial permeability to lucifer yellow (LY) dye. In addition, the SMSP2 group showed a significant decrease in the mRNA level of inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) in the Caco-2 monolayer compared to the LPS group. Moreover, SMSP2 increased the expression of the tight junctions (TJ) zonula occludens (ZO-1), occludin, and claudin-1 at the mRNA and protein levels. Furthermore, the immunofluorescence assay showed that SMSP2 ameliorated the overall distribution of the TJ proteins in the Caco-2 monolayer. SMSP2 application also resulted in the downregulation of the nuclear factor kappa-B (NF-κB) phosphorylation and the myosin light chain kinase (MLCK) expression, which implies that SMSP2 preserved the monolayer integrity from the inflammation-induced barrier disruption through the inhibition of the NF-kB-mediated MLCK signaling pathway activation. Senegalia macrostachya seeds could therefore be a promising functional food that could be used to improve intestinal barrier function.
研究领域:
药理学
·
免疫学
·
细胞生物学
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分子生物学
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胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yaru Zou,Wei Gao,Huizhen Jin,Chenmei Mao,Yi Zhang,Xiaoling Wang,Dong Mei,Libo Zhao
Background Nanomedicines have significant advantages in enhancing the oral bioavailability of drugs, but a deeper understanding of the underlying mechanisms remains to be interpreted. Hence, the present study aims to explain the uptake and trafficking mechanism for 6-MP nanomedicines we previously constructed.Methods 6-MP loaded poly(lactide-co-glycolide) (PLGA) nanomedicines (6-MPNs) were prepared by the multiple emulsion method. The transcytosis mechanism of 6-MPNs was investigated in Caco-2 cells, Caco-2 monolayers, follicle associated epithelium (FAE) monolayers and rats, including transmembrane pathway, intracellular trafficking, paracellular transport and the involvement of transporter.Results Pharmacokinetics in rats showed that the area under the curve (AUC) of 6-MP in the 6-MPNs group (147.3 ± 42.89 μg/L·h) was significantly higher than that in the 6-MP suspensions (6-MPCs) group (70.31 ± 18.24 μg/L·h). The uptake of 6-MPNs in Caco-2 cells was time-, concentration- and energy-dependent. The endocytosis of intact 6-MPNs was mediated mainly through caveolae/lipid raft, caveolin and micropinocytosis. The intracellular trafficking of 6-MPNs was affected by endoplasmic reticulum (ER)-Golgi complexes, late endosome-lysosome and microtubules. The multidrug resistance associated protein 4 (MRP4) transporter-mediated transport of free 6-MP played a vital role on the transmembrane of 6-MPNs. The trafficking of 6-MPNs from the apical (AP) side to the basolateral (BL) side in Caco-2 monolayers was obviously improved. Besides, 6-MPNs affected the distribution and expression of zona occludens-1 (ZO-1). The transport of 6-MPNs in FAE monolayers was concentration- and energy-dependent, while reaching saturation over time. 6-MPNs improved the absorption of the intestinal Peyer’s patches (PPs) in rats.Conclusion 6-MPNs improve the oral bioavailability through multiple pathways, including active transport, paracellular transport, lymphatic delivery and MRP4 transporter. The findings of current study may shed light on the cellular uptake and transcellular trafficking mechanism of oral nanomedicines.
研究领域:
药剂学
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药理学
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纳米技术
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细胞生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Fanghua Guo,Rong Tsao,Chuyao Li,Xiaoya Wang,Hua Zhang,Li Jiang,Yong Sun,Hua Xiong
Green pea hulls are a byproduct of the processing of green pea and are rich in phenolic substances. In the present study, in vitro digestion, human colonic adenocarcinoma cell line (Caco-2) monolayer, and the Caco-2/macrophage cell lines of the murine origin (Raw264.7) coculture model were established to investigate the release of polyphenols, absorption, and transport of digestive products and their effects on inflammation and intestinal barrier. During the digestive process, polyphenols were constantly released from the pea hulls, reaching the maximum amount in the small intestine (total phenolic content (TPC): 5.41 ± 0.04 mg gallic acid (GAE)/g dry weight (DW)), and the digestive products (800 μg/mL) could reduce the secretion of NO (50.9%), IL-6 (50.6%), and TNF-α (24.6%) and inhibit the mRNA expression of cyclooxygenase-2 (COX-2) (37.2%) and inducible nitric oxide synthase (iNOS) (91.1%) compared with the lipopolysaccharide (LPS) group. A total of 12 phenolic components were quantified by ultraperformance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry (UHPLC-LTQ-OrbiTrap-MS) technology. Kaempferol trihexoside in digestive products could be absorbed and transported (1.25 ± 0.13 ng quercetin/mL). The digestive products could promote the expression of claudin-1 (210.8%), occludin (64.9%), and zonulin occludin-1 (ZO-1) (52.0%) compared with the LPS group and exert anti-inflammatory effects after being absorbed. The results indicated that pea hull polyphenols could be continuously released and absorbed to play a positive role in protecting the intestinal barrier and anti-inflammatory activity.
研究领域:
食品科学
·
营养学
·
药理学
·
细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Zhongyuan Qu,Shuang Wu,Yan Zheng,Yifan Bing,Xueqin Liu,Sunan Li,Wenlan Li,Xiang Zou
Background Yueju Wan (YJW), defined in Danxi's Mastery of Medicine , has Qi-regulating and Qi-promoting effects. YJW has frequently been applied in the clinic for the treatment of depression. Substantial evidence has shown that depression is related to metabolic abnormalities of the gut microbiota , and traditional Chinese medicine (TCM) can treat depression by adjusting gut microbiota metabolism. The antidepressant effect of YJW is well established, but thus far, whether its mechanism of action is achieved by regulating the intestinal flora has not been elucidated. Methods In this study, chronic unpredictable mild stress (CUMS) along with isolated feeding created a rat depression model, and YJW was administered for intervention. Rats were put through behavioral tests to determine their level of depression, and ELISA was utilized for measuring the level of monoamine neurotransmitters (MNTs) in the hippocampus. Metagenomic gene sequencing analysis was used to study the effect of depression on the intestinal flora in rats and the regulatory mechanism of YJW on the intestinal flora. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was utilized for fecal metabolomics studies to further reveal the antidepressant mechanism of YJW. The antidepressant mechanism of YJW was explored and further verified by Western blot analysis . Results Different doses of YJW improved the depressive state of rats and raised the levels of MNTs in the hippocampus. The results of metagenomic sequencing indicated that the YJW recovered the structure and diversity of the intestinal flora in depressed rats. Metabolomics revealed sustained changes in 21 metabolites after the treatment of YJW, suggesting that YJW can play an antidepressant role by improving abnormal metabolic pathways. The results of correlation analysis suggested that YJW might mediate Eubacterium , Oscillibacter , Roseburia , Romboutsia and Bacterium to regulate purine metabolism, tryptophan metabolism, primary bile acid biosynthesis, and glutamate metabolism and exert antidepressant effects. Western blot analysis showed that YJW reduced the content of IL-1β in the hippocampus, inhibited the activation of the NLRP3 inflammasome in the hippocampus of rats, and increased the content of ZO-1 in the colon of rats. Conclusion YJW can alleviate depressive symptoms in depressed rats, and its mechanism is connected to improving intestinal flora and regulating body metabolism.
研究领域:
药理学
·
神经科学
·
微生物学
·
中医
·
代谢组学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Yue Su,Zhengying Cui,Xinyan Yang,Yujun Jiang,Wei Zhang,Yu Zhang,Chaoxin Man
Ulcerative colitis (UC) is an immune-mediated intestinal disease without a comprehensive cure, and the alleviation of UC has become an urgent problem. The results showed that JY062 with its EPS group (JEC) alleviated the intestinal barrier damage caused by LPS. After JEC intervention on Caco-2 cells, resulted in upregulation of ZO-1, Claudin-1, Occludin and MUC2 transcript levels and decreased mRNA expression of Claudin-2 (p < 0.05). JEC effectively attenuated the inflammatory response in UC mice and restoration of immunoglobulin levels (IgG, IgM and IgA), which resulted in shortening and swelling of the colon, disappearance of goblet cells, infiltration of inflammatory cells and mucosal damage were alleviated in mice. Similarly, changes in the expression of MUC2 and tight junction proteins after JEC intervention also occurred in UC mice. Administration of JEC significantly inhibited the differentiation of pro-inflammatory Th17 cells in the thymus and peripheral blood, promoted the differentiation of CD4+ T cells to Treg cells, and effectively regulated DSS-induced macrophage imbalance, which was manifested by the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages. This study clearly demonstrates that JEC could significantly prevent intestinal barrier on DSS-induced experimental colitis and could be applied as a potential symbiotic strategy to assist in the alleviation of UC.
研究领域:
微生物学
·
免疫学
·
胃肠病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）