吴茱萸碱改善能量代谢修复TNBS诱导大鼠结肠炎结肠黏膜损伤的作用机制
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摘要
目的:观察三硝基苯磺酸(TNBS)诱导的实验性结肠炎大鼠结肠黏膜能量代谢变化,探讨吴茱萸碱(EVO)修复其结肠黏膜的作用机制。方法:将40只雄性SD大鼠随机平均分为正常组、模型组、EVO组、美沙拉嗪组,除正常组外,其余均用TNBS/乙醇复合法诱导实验性结肠炎模型,并于造模成功后第1天给予药物干预,时间1周。观察大鼠一般情况及结肠黏膜大体形态,分别采用考马斯亮蓝法检测总蛋白量、化学比色法检测ATP含量及ALDH、SDH、Na+-K+-ATPase和Ca2+-Mg2+-ATPase活力变化;同时采用ELISA法检测EGF、TGF-β1、IGF-1水平变化。结果:与模型组比较,EVO可有效改善TNBS诱导的实验性结肠炎大鼠一般情况和结肠黏膜损伤,提高结肠黏膜IGF-1水平、降低EGF、TGF-β1水平(P<0.05);同时伴见结肠黏膜ATP含量及ALDH活力显著下降(P<0.01,P<0.05),SDH、Na+-K+-ATPase和Ca2+-Mg2+-ATPase活力提升(P<0.05)。结论:EVO可有效修复TNBS诱导的实验性结肠炎大鼠结肠黏膜,抑制黏膜组织过度增生,其作用机制与EVO对结肠黏膜能量代谢调节有关,这也为吴茱萸治疗溃疡性结肠炎提供药理学证据。
Objective: To study the effects of the energy metabolism and discuss the mechanism of evodiamine(EVO)repairing colon mucosa on colitis in rats with colitis. Methods: Fourty SD male rats were randomly divided into four groups: the normal group, the model group, the EVO group and the SASP group. The colitis model was established with TNBS/ethanol except the normal group. The drug intervention was given on the first day after modeling for 1 week. The general conditions and the morphology of colon mucosa damage were observed to evaluate the therapeutic effect of EVO, the total of ATP, ALDH, SDH,Na+-K+-ATPase, Ca2+-Mg2+-ATPase in colonic mucosa were tested by chemical colorimetry, EGF, TGF-β1, IGF-1 were detected by ELISA. Results: Compared with model group, the general condition and the morphology of colon mucosa damage in the EVO group were significantly increased, Meanwhile, after rats with colitis treated by EVO, the concentration of IGF-1 was increased,the average levels of EGF and TGF-β1 were decreased(P<0.05), the activity of SDH, Na+-K+-ATPase, and the concentrations of ATP and ALDH were obviously decreased(P<0.01, P<0.05), Ca2+-Mg2+-ATPase were increased(P<0.05). Conclusion: EVO can effectively repair the colonic mucosa and inhibited the hyperplasia of mucosa tissues in experimental colitis rats, the mechanism maybe related with the energy metabolism of the colonic mucosa by EVO, which also provides pharmacological evidence for the treatment of UC by Fructus Evodiae.
Objective: To study the effects of the energy metabolism and discuss the mechanism of evodiamine(EVO)repairing colon mucosa on colitis in rats with colitis. Methods: Fourty SD male rats were randomly divided into four groups: the normal group, the model group, the EVO group and the SASP group. The colitis model was established with TNBS/ethanol except the normal group. The drug intervention was given on the first day after modeling for 1 week. The general conditions and the morphology of colon mucosa damage were observed to evaluate the therapeutic effect of EVO, the total of ATP, ALDH, SDH,Na+-K+-ATPase, Ca2+-Mg2+-ATPase in colonic mucosa were tested by chemical colorimetry, EGF, TGF-β1, IGF-1 were detected by ELISA. Results: Compared with model group, the general condition and the morphology of colon mucosa damage in the EVO group were significantly increased, Meanwhile, after rats with colitis treated by EVO, the concentration of IGF-1 was increased,the average levels of EGF and TGF-β1 were decreased(P<0.05), the activity of SDH, Na+-K+-ATPase, and the concentrations of ATP and ALDH were obviously decreased(P<0.01, P<0.05), Ca2+-Mg2+-ATPase were increased(P<0.05). Conclusion: EVO can effectively repair the colonic mucosa and inhibited the hyperplasia of mucosa tissues in experimental colitis rats, the mechanism maybe related with the energy metabolism of the colonic mucosa by EVO, which also provides pharmacological evidence for the treatment of UC by Fructus Evodiae.
引文
[1]中华中医药学会脾胃病分会.溃疡性结肠炎中医诊疗专家共识意见(2017).中华中医药杂志,2017,32(8):3585-3589
[2]刘继东,苗嘉芮,李宁,等.脾虚模型大鼠能量代谢相关性基因研究.中华中医药杂志,2015,30(9):3304-3306
[3]姜旭光,姜明霞,王枫.干扰上皮细胞能量代谢对炎症性肠病发病的影响.世界华人消化杂志,2015,23(27):4393-4398
[4]黄丽萍,余日跃,李森,等.利血平所致大鼠虚寒证模型的研究及热药吴茱萸的干预作用.中华中医药杂志,2014,29(11):3416-3419
[5]黄丽萍,余日跃,彭淑红,等.热药吴茱萸对利血平所致虚寒证大鼠肝脏能量代谢相关机制的影响.中国中药杂志,2013,38(20):3539-3543
[6]Mi H,Liu F B,Li H W,et al.Anti-inflammatory effect of ChangAn-Shuan on TNBS-induced experimental colitis in rats.BMC Complement Altern Med,2017,17(1):315
[7]范颖,李楠,孙云峰,等.黄芪有效部位对糖尿病大鼠Na+-K+-ATP酶活性及AMPK蛋白表达的影响.中华中医药杂志,2012,27(10):3660-3663
[8]Feissner R F,Skalska J,Gaum W E,et al.Crosstalk signaling between mitochondrial Ca2+and ROS.Front Biosci,2009,14:1197-1218
[9]Yashiro M.Ulcerative colitis-associated colorectal cancer.World J Gastroenterol,2014,20(44):16389-16397
[10]Huang E H,Hynes M J,Zhang T,et al.Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells(SC)and tracks SC overpopulation during colon tumorigenesis.Cancer Res,2009,69(8):3382-3389
[11]DubéP E,Liu C Y,Girish N,et al.Pharmacological activation of epidermal growth factor receptor signaling inhibits colitisassociated cancer in mice.Sci Rep,2018,8(1):9119
[12]Chru?cik A,Gopalan V,Lam A K.The clinical and biological roles of transforming growth factor beta in colon cancer stem cells:A systematic review.Eur J Cell Biol,2018,97(1):15-22
[13]Katsanos K H,Tsatsoulis A,Christodoulou D,et al.Reduced serum insulin-like growth factor-1(IGF-1)and IGF-binding protein-3 levels in adults with inflammatory bowel disease.Growth Horm IGF Res,2001,11(6):364-367
[14]Chen T,Zheng F,Tao J,et al.Insulin-like growth factor1 contributes to mucosal repair byβ-arrestin2-mediated extracellular signalrelated kinase signaling in experimental colitis.Am J Pathol,2015,185(9):2441-2453
[15]徐俊杰,杨然,杨芳景,等.吴茱萸碱抗肿瘤机制的研究进展.上海交通大学学报(医学版),2018,38(5):578-583
[16]滕之颖,蔡雪婷,杨洋,等.吴茱萸碱对炎症相关性结直肠癌的预防作用研究.南京中医药大学学报,2015,31(3):234-237
[17]Huang C,Liu H,Gong X L,et al.Effect of evodiamine and berberine on the interaction between DNMTs and target micro RNAs during malignant transformation of the colon by TGF-β1.Oncol Rep,2017,37(3):1637-1645
[18]赵平,董蕾,罗金燕,等.DSS与TNBS诱导大鼠实验性结肠炎模型的对比研究.胃肠病学,2015,20(11):667-671
[2]刘继东,苗嘉芮,李宁,等.脾虚模型大鼠能量代谢相关性基因研究.中华中医药杂志,2015,30(9):3304-3306
[3]姜旭光,姜明霞,王枫.干扰上皮细胞能量代谢对炎症性肠病发病的影响.世界华人消化杂志,2015,23(27):4393-4398
[4]黄丽萍,余日跃,李森,等.利血平所致大鼠虚寒证模型的研究及热药吴茱萸的干预作用.中华中医药杂志,2014,29(11):3416-3419
[5]黄丽萍,余日跃,彭淑红,等.热药吴茱萸对利血平所致虚寒证大鼠肝脏能量代谢相关机制的影响.中国中药杂志,2013,38(20):3539-3543
[6]Mi H,Liu F B,Li H W,et al.Anti-inflammatory effect of ChangAn-Shuan on TNBS-induced experimental colitis in rats.BMC Complement Altern Med,2017,17(1):315
[7]范颖,李楠,孙云峰,等.黄芪有效部位对糖尿病大鼠Na+-K+-ATP酶活性及AMPK蛋白表达的影响.中华中医药杂志,2012,27(10):3660-3663
[8]Feissner R F,Skalska J,Gaum W E,et al.Crosstalk signaling between mitochondrial Ca2+and ROS.Front Biosci,2009,14:1197-1218
[9]Yashiro M.Ulcerative colitis-associated colorectal cancer.World J Gastroenterol,2014,20(44):16389-16397
[10]Huang E H,Hynes M J,Zhang T,et al.Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells(SC)and tracks SC overpopulation during colon tumorigenesis.Cancer Res,2009,69(8):3382-3389
[11]DubéP E,Liu C Y,Girish N,et al.Pharmacological activation of epidermal growth factor receptor signaling inhibits colitisassociated cancer in mice.Sci Rep,2018,8(1):9119
[12]Chru?cik A,Gopalan V,Lam A K.The clinical and biological roles of transforming growth factor beta in colon cancer stem cells:A systematic review.Eur J Cell Biol,2018,97(1):15-22
[13]Katsanos K H,Tsatsoulis A,Christodoulou D,et al.Reduced serum insulin-like growth factor-1(IGF-1)and IGF-binding protein-3 levels in adults with inflammatory bowel disease.Growth Horm IGF Res,2001,11(6):364-367
[14]Chen T,Zheng F,Tao J,et al.Insulin-like growth factor1 contributes to mucosal repair byβ-arrestin2-mediated extracellular signalrelated kinase signaling in experimental colitis.Am J Pathol,2015,185(9):2441-2453
[15]徐俊杰,杨然,杨芳景,等.吴茱萸碱抗肿瘤机制的研究进展.上海交通大学学报(医学版),2018,38(5):578-583
[16]滕之颖,蔡雪婷,杨洋,等.吴茱萸碱对炎症相关性结直肠癌的预防作用研究.南京中医药大学学报,2015,31(3):234-237
[17]Huang C,Liu H,Gong X L,et al.Effect of evodiamine and berberine on the interaction between DNMTs and target micro RNAs during malignant transformation of the colon by TGF-β1.Oncol Rep,2017,37(3):1637-1645
[18]赵平,董蕾,罗金燕,等.DSS与TNBS诱导大鼠实验性结肠炎模型的对比研究.胃肠病学,2015,20(11):667-671