| 莫霏霏,周晶晶,金玲玲,余光.栀子苷对溃疡性结肠炎大鼠的抗炎作用及AMPK/MLCK信号通路的影响[J].浙江中西医结合杂志,2021,31(5): |
| 栀子苷对溃疡性结肠炎大鼠的抗炎作用及AMPK/MLCK信号通路的影响 |
| Anti-inflammatory effect of geniposide on rats with ulcerative colitis and its effect on AMPK/MLCK signaling pathway |
| 投稿时间：2020-10-05 修订日期：2021-04-12 |
| DOI： |
| 中文关键词: 栀子苷 溃疡性结肠炎 腺苷酸激活蛋白激酶 肌球蛋白轻链激酶 |
| 英文关键词:Geniposide Ulcerative colitis Adenosine monophosphate-activated protein kinase Myosin light chain kinase |
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| 中文摘要: |
| 目的 探讨栀子苷对溃疡性结肠炎大鼠的抗炎作用及腺苷酸激活蛋白激酶(AMPK)/肌球蛋白轻链激酶(MLCK)信号通路的影响。方法 90只SD只大鼠随机分成对照组、模型组、柳氮磺胺吡啶组(300mg?kg-1)、栀子苷低、高剂量组(40、80mg?kg-1),每组18只；模型组、柳氮磺胺吡啶组、栀子苷低剂量组、栀子苷高剂量组用2,4,6-三硝基苯磺酸(TNBS)诱导溃疡性结肠炎模型,建模成功后,柳氮磺胺吡啶组、栀子苷低、高剂量组给予相应药物灌胃,持续4周,对照组及模型组给予等体积的生理盐水。试验结束后,测定各组大鼠结肠黏膜损伤指数、疾病活动指数(DAI)评分、大体形态损伤评分,采用逆转录-聚合酶链反应(RT-PCR)法及蛋白免疫印迹(WB)法测定大鼠肠黏膜AMPK、MLCK mRNA和蛋白水平,酶联免疫吸附试验(ELISA)法测定白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。结果 与对照组比较,模型组结肠黏膜损伤指数、DAI评分、大体形态损伤评分、结肠组织MLCK mRNA和蛋白表达水平、IL-2、IL-6、TNF-α水平升高(P<0.05),AMPK mRNA和蛋白表达水平降低(P<0.05)；与模型组比较,柳氮磺胺吡啶组、栀子苷低剂量组、栀子苷高剂量组结肠黏膜损伤指数、DAI评分、大体形态损伤评分、结肠组织MLCK mRNA和蛋白表达水平、IL-2、IL-6、TNF-α水平降低(P<0.05),AMPK mRNA和蛋白表达水平升高(P<0.05)；且栀子苷高剂量组结肠黏膜损伤指数、DAI评分、大体形态损伤评分、结肠组织MLCK mRNA和蛋白表达水平、IL-2、IL-6、TNF-α水平低于栀子苷低剂量组(P<0.05),AMPK mRNA和蛋白表达水平高于栀子苷低剂量组(P<0.05)；与柳氮磺胺吡啶组比较,栀子苷低剂量组结肠黏膜损伤指数、DAI评分、大体形态损伤评分、结肠组织MLCK mRNA和蛋白表达水平、IL-2、IL-6、TNF-α水平升高(P<0.05),AMPK mRNA和蛋白表达水平降低(P<0.05)；栀子苷高剂量组和柳氮磺胺吡啶组结肠黏膜损伤指数、DAI评分、大体形态损伤评分、结肠组织AMPK、MLCK mRNA和蛋白表达、IL-2、IL-6、TNF-α水平比较差异无统计学意义(P>0.05)。结论 栀子苷能抑制溃疡性结肠炎大鼠肠道损伤及炎症反应；其机制与栀子苷可能增强了AMPK mRNA和蛋白表达,抑制了MLCK mRNA和蛋白表达,进而抑制了AMPK/MLCK信号通路有关。 |
| 英文摘要: |
| Objective: To investigate the Anti-inflammatory effect of geniposide on rats with ulcerative colitis and its effect on adenosine monophosphate-activated protein kinase(AMPK)/myosin light chain kinase(MLCK) signaling pathway. Methods: 90 SD rats were random divided into control group, model group, sulfasalazine group (300mg?kg-1), gardenoside low-dose group and high-dose group (40, 80mg?kg-1), 18 in each group. The rats in the model group, sulfasalazine group, low-dose gardenoside group and high-dose gardenoside group were induced by TNBS to establish Ulcerative colitis model. After successful modeling, the rats in the sulfasalazine group, low-dose gardenoside group and high-dose gardenoside group were given corresponding drugs by gavage for 4 weeks. The rats in the control group and model group were given the same volume of saline. After the experiment, the intestinal mucosal damage index, disease activity index(DAI) score and gross morphological damage score were measured. The levels of AMPK, MLCK mRNA and protein in intestinal mucosa were measured by reverse transcription-polymerase chain reaction(RT-PCR) and western blot(WB). The levels of interleukin-2(IL-2), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). Results: Compared with the control group, the colonic mucosal injury index, DAI score and gross morphological damage score, expression level of MLCK mRNA and protein, level of IL-2、IL-6、TNF-α in colon of the model group were increased(P<0.05), expression level of AMPK mRNA and protein were decreased(P<0.05). Compare with the model group, the colonic mucosal injury index, DAI score and gross morphological damage score, expression level of MLCK mRNA and protein, level of IL-2、IL-6、TNF-α in colon of the sulfasalazine group, low-dose geniposide group and high-dose geniposide group were decreased(P<0.05), expression level of AMPK mRNA and protein were increased(P<0.05). And the colonic mucosal injury index, DAI score and gross morphological damage score, expression level of MLCK mRNA and protein, level of IL-2、IL-6、TNF-α in colon of high-dose geniposide group were lower than low-dose geniposide group(P<0.05), expression level of AMPK mRNA and protein were higher than low-dose geniposide group(P<0.05). Compare with the sulfasalazine group, the colonic mucosal injury index, DAI score and gross morphological damage score, expression level of MLCK mRNA and protein, level of IL-2、IL-6、TNF-α in colon of low-dose geniposide group were increased(P<0.05), expression level of AMPK mRNA and protein were decreased(P<0.05). There was no significant difference between the high-dose geniposide group and sulfasalazine group(P > 0.05). Conclusion: Geniposide can inhibit intestinal injury and inflammation in rats with ulcerative colitis, and its mechanism is related to the enhancement of AMPK mRNA and protein and the inhibition of the expression of MLCK mRNA and protein, thereby inhibiting the AMPK/MLCK signaling pathway by Geniposide. |
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