干酪乳杆菌Qian增强京尼平苷对盐酸/乙醇诱导小鼠胃损伤的预防效果（英文）
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摘要
为探讨最近新发现的干酪乳杆菌Qian(Lactobacillus casei Qian,LC-Qian)和京尼平苷组合对胃损伤预防效果的增强作用,比较分析LC-Qian(0.5×10~8 CFU/kg,以体质量计,下同)、京尼平苷(50 mg/kg)以及LC-Qian(0.5×10~8 CFU/kg)+京尼平苷(50 mg/kg)对盐酸/乙醇诱导胃损伤的预防效果。LC-Qian+京尼平苷(组合组)能减少胃损伤面积和胃液量,同时提高胃液pH值,能使这些指标接近正常组并且与模型组显著不同。相对于模型组,组合组能降低细胞因子白细胞介素-6(interleukin-6,IL-6)、IL-12、肿瘤坏死因子α和γ-干扰素的水平,同时降低血清胃动素、P物质、内皮素-1的水平和提高生长激素抑制素、血管活性肠肽的水平。相比模型组,在心脏、肝脏、肾脏和胃组织中组合组表现出更高的NO含量,但是这些含量低于正常组。通过逆转录聚合酶链式反应分析观察到:相对于对照组小鼠,组合组能够上调神经元型一氧化氮合酶、内皮型一氧化氮合酶、核因子κB抑制蛋白α的mRNA表达和下调诱导型一氧化氮合成酶、核因子κB表达,同时以上这些表达强度与正常组较为接近。通过这些结果可以看到LC-Qian和京尼平苷联合使用具有最好的胃损伤预防效果,LC-Qian能够提高京尼平苷的胃损伤预防效果,该组合可作为一种新的参考方法用于预防胃损伤。
The aim of this study was to investigate the synergistic effect of a recently discovered strain Lactobacillus casei Qian(LC-Qian) and geniposide on the prevention of ethanol-induced gastric injury in mice.LC-Qian(0.5 × 108 CFU/kg m_b) was mixed with geniposide(50 mg/kg mb),and LC-Qian(0.5 × 108 CFU/kg m_b) and geniposide(50 mg/kg m_b) were also used separately to protect against HCl/ethanol induced gastric injury and to compare their preventive effects.LC-Qian combined with geniposide(the combination group) diminished the gastric lesion area and gastric secretion volume and raised the p H of the gastric juice to a level close of that of the control group and significantly different from that in the model group.The combination treatment was also able to decrease the serum levels of cytokines such as interleukin-6(IL-6),IL-12,tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ),motilin(MOT),substance P(SP),and endothelin-1(ET-1) but increase the levels of somatostatin(SS) and vasoactive intestinal peptide(VIP) as compared to the model group.The combination group showed higher NO contents in serum,heart,liver,kidney and stomach in comparison to the model group,but their levels were lower than those in the normal group.As indicated by reverse transcription polymerase chain reaction(RT-PCR) assay,the combination treatment could increase the m RNA expression levels of neuronal nitric oxide synthase(nNOS),endothelial NOS(eNOS) and inhibitor kappa B-α(IκB-α),and decrease the m RNA expression levels of inducible nitric oxide synthase NOS(iNOS) and nuclear factor kappa B(NF-κB) as compared to the model group.These expression levels in the combination group were similar to those of the normal group.From these results,it can be concluded that the combination treatment has the best preventive effects against gastric injury and LC-Qian could enhance the preventive effect of geniposide against gastric injury.Therefore,this combination treatment could be used as a new way method for the prevention of gastric injury.
The aim of this study was to investigate the synergistic effect of a recently discovered strain Lactobacillus casei Qian(LC-Qian) and geniposide on the prevention of ethanol-induced gastric injury in mice.LC-Qian(0.5 × 108 CFU/kg m_b) was mixed with geniposide(50 mg/kg mb),and LC-Qian(0.5 × 108 CFU/kg m_b) and geniposide(50 mg/kg m_b) were also used separately to protect against HCl/ethanol induced gastric injury and to compare their preventive effects.LC-Qian combined with geniposide(the combination group) diminished the gastric lesion area and gastric secretion volume and raised the p H of the gastric juice to a level close of that of the control group and significantly different from that in the model group.The combination treatment was also able to decrease the serum levels of cytokines such as interleukin-6(IL-6),IL-12,tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ),motilin(MOT),substance P(SP),and endothelin-1(ET-1) but increase the levels of somatostatin(SS) and vasoactive intestinal peptide(VIP) as compared to the model group.The combination group showed higher NO contents in serum,heart,liver,kidney and stomach in comparison to the model group,but their levels were lower than those in the normal group.As indicated by reverse transcription polymerase chain reaction(RT-PCR) assay,the combination treatment could increase the m RNA expression levels of neuronal nitric oxide synthase(nNOS),endothelial NOS(eNOS) and inhibitor kappa B-α(IκB-α),and decrease the m RNA expression levels of inducible nitric oxide synthase NOS(iNOS) and nuclear factor kappa B(NF-κB) as compared to the model group.These expression levels in the combination group were similar to those of the normal group.From these results,it can be concluded that the combination treatment has the best preventive effects against gastric injury and LC-Qian could enhance the preventive effect of geniposide against gastric injury.Therefore,this combination treatment could be used as a new way method for the prevention of gastric injury.
引文
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[13]ROCCO A,COMPARE D,ANGRISANI D,et al.Alcoholic disease:liver and beyond[J].World Journal of Gastroenterology,2014,20(4):14652-14659.DOI:10.3748/wjg.v20.i40.14652.
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[15]QIAN Y,SUO H Y,DU M Y,et al.Preventive effect of Lactobacillus fermentum Lee on activated carbon-induced constipation in mice[J].Experimental and Therapeutic Medicine,2015,61(9):272-278.DOI:10.3892/etm.2014.2064.
[16]ZHANG W X,CHEN Y Q,CHEN B,et al.Protective effect of geniposide on liver injury induced by triptolide[J].Pharmacology and Clinics of Chinese Materia Medica,2014,30(3):69-75.DOI:10.13412/j.cnki.zyyl.2014.03.022.
[17]ZHANG H X.Protective effects of genipin on diabetic nephropathy in mice[J].Herald of Medicine,2015,34(1):26-30.
[18]LU P J,HSU P I,CHEN C H,et al.Gastric juice acidity in upper gastrointestinal diseases[J].World Journal of Gastroenterology,2010,16(43):5496-5501.DOI:10.3748/wjg.v16.i43.5496.
[19]CHEN S,ZHU K,WANG R,et al.Preventive effect of polysaccharides from the large yellow croaker swim bladder on HCl/ethanol induced gastric injury in mice[J].Experimental and Therapeutic Medicine,2014,8(1):316-322.DOI:10.3892/etm.2014.1712.
[20]LIANG J,LI Y,LIU X L,et al.Relationship between cytokine levels and clinical classification of gastric cancer[J].Asian Pacific Journal of Cancer Prevention,2011,12(7):1803-1806.
[21]WANG F Y,LIU J M,LUO H H,et al.Potential protective effects of Clostridium butyricum on experimental gastric ulcers in mice[J].World Journal of Gastroenterology,2015,21(27):8340-8351.DOI:10.3748/wjg.v21.i27.8340.
[22]SUN L,WU Q,HAN B,et al.Mechanisms of immune injury and heterogeneity of bone marrow hematopoietic cells island in patients with auto-immuno-related hematocytopenia[J].Journal of Immunoassay and Immunochemistry,2014,35(4):378-387.DOI:10.1080/15321819.2014.899251.
[23]LINDGREN A,YUN C H,SJOLING A,et al.Impaired IFN-γ production after stimulation with bacterial components by natural killer cells from gastric cancer patients[J].Experimental Cell Research,2011,317(6):849-858.DOI:10.1016/j.yexcr.2011.01.006.
[24]LI G J,SUN P,WANG R,et al.Preventive effect of polysaccharide of Larimichthys crocea swim bladder on reserpine induced gastric ulcer in ICR mice[J].Korean Journal of Physiology&Pharmacology,2014,18(2):183-190.DOI:10.4196/kjpp.2014.18.2.183.
[25]ZHOU Y L,WANG R,FENG X,et al.Preventive effect of insect tea against reserpine-induced gastric ulcers in mice[J].Experimental and Therapeutic Medicine,2014,8(4):1318-1324.DOI:10.3892/etm.2014.1859.
[26]FENG Xia,ZHAO Xin.Preventive effect of Ilex kudingcha C.J.Tseng on gastric injury SD-rats[J].Modern Food Science and Technology,2014,30(4):21-25.
[27]DU Y,ZHAO W,LU L,et al.Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-α(TNF-α)and endothelin-1(ET-1)[J].Asian Pacific Journal of Tropical Biomedicine,2013,3(12):925-930.DOI:10.1016/S2221-1691(13)60180-X.
[28]LOPEZ-BELMONTE J,WHITTLE B J,MONCADA S.The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa[J].British Journal of Pharmacology,1993,108(1):73-78.DOI:10.1111/j.1476-5381.
[29]FENG C J.Mechanism of nitric oxide synthase regulation:electron transfer and interdomain interactions[J].Coordination Chemistry Reviews,2012,256(3/4):393-411.DOI:10.1016/j.ccr.2011.10.011.
[30]HAJREZAIE M,GOLBABAPOUR S,HASSANDARVISH P,et al.Acute toxicity and gastroprotection studies of a new schiff base derived copper(Ⅱ)complex against ethanol-induced acute gastric lesions in rats[J].PLo SONE,2012,7(12):1-11.DOI:10.1371/journal.pone.0051537.
[31]LIU Y,GOU L S,YIN C,et al.A preliminary study on protective effect of L-citrulline against ischemia-reperfusion induced gastric mucosal lesions in rat[J].Indian Journal of Pharmacology,2012,44(1):31-35.DOI:10.4103/0253-7613.91863.
[32]GUPTA S C,SUNDARAM C,REUTER S,et al.Inhibiting NF-κB activation by small molecules as a therapeutic strategy[J].Biochimica et Biophysica Acta,2010(10/11/12):775-787.DOI:10.1016/j.bbagrm.2010.05.004.
[33]CHOI Y H,KIM G Y,LEE H H.Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-κB signaling pathways[J].Drug Design,Development and Therapy,2014,8:1941-1953.
[34]GAMBHIR S,VYAS D,HOLLIS M,et al.Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies[J].World Journal of Gastroenterology,2015,21(11):3174-3183.DOI:10.3748/wjg.v21.i11.3174.
[2]MENG X L,LI H W,LI Y,et al.Advances in studies on chemical constituents and pharmacological activities of Gardenia jasminoides[J].Chinese Journal of New Drugs,2011,20(11):959-967.
[3]LIU Y R,DING K Y,LIU J.Research on extraction and adsorption of geniposide from Sichuan Gardenia[J].Natural Product Research and Development,2014,26(11):1806;1864-1867.DOI:10.16333/j.1001-6880.2014.11.020.
[4]ZHENG L S,NI N,LIU X Q,et al.Study and application of geniposide and genipin[J].Drug Evaluation Research,2012,35(4):289-298.
[5]WANG G F,WU S Y,XU W,et al.Geniposide inhibits high glucoseinduced cell adhesion through the NF-κB signaling pathway in human umbilical vein endothelial cells[J].Acta Pharmacologica Sinica,2010,31(8):953-962.DOI:10.1038/aps.2010.83.
[6]WANG Yonghong,SU Jian,WANG Jianfang,et al.Studies on the microbial transform ation of geniposide in gordenis[J].Lishizhen Medicine&Materia Medica Research,2007,18(12):3003-3004.
[7]WAN Z T,YANG L J.Sereening lactic acid bacteria to produce extracellularβ-glucosidase and the preliminary studies of the enzyme properties[J].Food and Fermentation Industries,2009,35(4):28-32.DOI:10.13995/j.cnki.11-1802/ts.2009.04.015.
[8]ZHAO X,SUO H Y,QIAN Y,et al.Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon induced constipated mice[J].Molecular Medicine Reports,2015,12(2):191-199.DOI:10.3892/mmr.2015.3737.
[9]FREDERICA V,KHOSROW K,NIHARIKA N.The dual role of i NOS in cancer[J].Redox Biology,2015,6:334-343.DOI:10.1016/j.redox.2015.08.009.
[10]MA S T,YANG D C,LI D,et al.Inhibition of uncoupling protein2 with genipin exacerbates palmitate-induced hepatic steatosis[J].Lipids in Health and Disease,2012,11(1):154.DOI:10.1186/1476-511X-11-154.
[11]KOO H J,SONG Y S,KIM H J,et al.Antiinflammatory effects of genipin,an active principle of gardenia[J].European Journal of Pharmacology,2004,495(2/3):201-208.
[12]ZHOU Yanan,ZHANG Weiming,QIAN Hua,et al.Research advanceson pharmacological activities of geniposide and its derivatives[J].Chinese Wild Plant Resources,2011,30(1):1-4.
[13]ROCCO A,COMPARE D,ANGRISANI D,et al.Alcoholic disease:liver and beyond[J].World Journal of Gastroenterology,2014,20(4):14652-14659.DOI:10.3748/wjg.v20.i40.14652.
[14]LIEBER C S.Gastric ethanol metabolism and gastritis:interactions with other drugs,Helicobacter pylori,and antibiotic therapy(1957-1997):a review[J].Alcoholism Clinical and Experimental Research,1997,21(8):1360-1366.
[15]QIAN Y,SUO H Y,DU M Y,et al.Preventive effect of Lactobacillus fermentum Lee on activated carbon-induced constipation in mice[J].Experimental and Therapeutic Medicine,2015,61(9):272-278.DOI:10.3892/etm.2014.2064.
[16]ZHANG W X,CHEN Y Q,CHEN B,et al.Protective effect of geniposide on liver injury induced by triptolide[J].Pharmacology and Clinics of Chinese Materia Medica,2014,30(3):69-75.DOI:10.13412/j.cnki.zyyl.2014.03.022.
[17]ZHANG H X.Protective effects of genipin on diabetic nephropathy in mice[J].Herald of Medicine,2015,34(1):26-30.
[18]LU P J,HSU P I,CHEN C H,et al.Gastric juice acidity in upper gastrointestinal diseases[J].World Journal of Gastroenterology,2010,16(43):5496-5501.DOI:10.3748/wjg.v16.i43.5496.
[19]CHEN S,ZHU K,WANG R,et al.Preventive effect of polysaccharides from the large yellow croaker swim bladder on HCl/ethanol induced gastric injury in mice[J].Experimental and Therapeutic Medicine,2014,8(1):316-322.DOI:10.3892/etm.2014.1712.
[20]LIANG J,LI Y,LIU X L,et al.Relationship between cytokine levels and clinical classification of gastric cancer[J].Asian Pacific Journal of Cancer Prevention,2011,12(7):1803-1806.
[21]WANG F Y,LIU J M,LUO H H,et al.Potential protective effects of Clostridium butyricum on experimental gastric ulcers in mice[J].World Journal of Gastroenterology,2015,21(27):8340-8351.DOI:10.3748/wjg.v21.i27.8340.
[22]SUN L,WU Q,HAN B,et al.Mechanisms of immune injury and heterogeneity of bone marrow hematopoietic cells island in patients with auto-immuno-related hematocytopenia[J].Journal of Immunoassay and Immunochemistry,2014,35(4):378-387.DOI:10.1080/15321819.2014.899251.
[23]LINDGREN A,YUN C H,SJOLING A,et al.Impaired IFN-γ production after stimulation with bacterial components by natural killer cells from gastric cancer patients[J].Experimental Cell Research,2011,317(6):849-858.DOI:10.1016/j.yexcr.2011.01.006.
[24]LI G J,SUN P,WANG R,et al.Preventive effect of polysaccharide of Larimichthys crocea swim bladder on reserpine induced gastric ulcer in ICR mice[J].Korean Journal of Physiology&Pharmacology,2014,18(2):183-190.DOI:10.4196/kjpp.2014.18.2.183.
[25]ZHOU Y L,WANG R,FENG X,et al.Preventive effect of insect tea against reserpine-induced gastric ulcers in mice[J].Experimental and Therapeutic Medicine,2014,8(4):1318-1324.DOI:10.3892/etm.2014.1859.
[26]FENG Xia,ZHAO Xin.Preventive effect of Ilex kudingcha C.J.Tseng on gastric injury SD-rats[J].Modern Food Science and Technology,2014,30(4):21-25.
[27]DU Y,ZHAO W,LU L,et al.Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-α(TNF-α)and endothelin-1(ET-1)[J].Asian Pacific Journal of Tropical Biomedicine,2013,3(12):925-930.DOI:10.1016/S2221-1691(13)60180-X.
[28]LOPEZ-BELMONTE J,WHITTLE B J,MONCADA S.The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa[J].British Journal of Pharmacology,1993,108(1):73-78.DOI:10.1111/j.1476-5381.
[29]FENG C J.Mechanism of nitric oxide synthase regulation:electron transfer and interdomain interactions[J].Coordination Chemistry Reviews,2012,256(3/4):393-411.DOI:10.1016/j.ccr.2011.10.011.
[30]HAJREZAIE M,GOLBABAPOUR S,HASSANDARVISH P,et al.Acute toxicity and gastroprotection studies of a new schiff base derived copper(Ⅱ)complex against ethanol-induced acute gastric lesions in rats[J].PLo SONE,2012,7(12):1-11.DOI:10.1371/journal.pone.0051537.
[31]LIU Y,GOU L S,YIN C,et al.A preliminary study on protective effect of L-citrulline against ischemia-reperfusion induced gastric mucosal lesions in rat[J].Indian Journal of Pharmacology,2012,44(1):31-35.DOI:10.4103/0253-7613.91863.
[32]GUPTA S C,SUNDARAM C,REUTER S,et al.Inhibiting NF-κB activation by small molecules as a therapeutic strategy[J].Biochimica et Biophysica Acta,2010(10/11/12):775-787.DOI:10.1016/j.bbagrm.2010.05.004.
[33]CHOI Y H,KIM G Y,LEE H H.Anti-inflammatory effects of cordycepin in lipopolysaccharide-stimulated RAW 264.7 macrophages through Toll-like receptor 4-mediated suppression of mitogen-activated protein kinases and NF-κB signaling pathways[J].Drug Design,Development and Therapy,2014,8:1941-1953.
[34]GAMBHIR S,VYAS D,HOLLIS M,et al.Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies[J].World Journal of Gastroenterology,2015,21(11):3174-3183.DOI:10.3748/wjg.v21.i11.3174.