| 葛相栓,刘小玲,王慧超,等.吡格列酮对三硝基苯磺酸诱导炎症性肠病大鼠过氧化物酶体增殖物激活受体 γ和核因子?κB p65的影响[J].安徽医药,2019,23(10):1921-1925. |
| 吡格列酮对三硝基苯磺酸诱导炎症性肠病大鼠过氧化物酶体增殖物激活受体 γ和核因子?κB p65的影响 |
| Effects of pioglitazone on expression of PPAR?γ and NF?κB p65 in rats with inflammatory bowel disease induced by TNBS |
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| DOI：10.3969/j.issn.1009?6469.2019.10.004 |
| 中文关键词: 炎性肠病 吡格列酮 过氧化物酶体增殖物激活受体 NF-κB 转录因子 RelA 三硝基苯磺酸 柳氮磺胺吡啶 细胞保护 大鼠，Sprague?Dawley |
| 英文关键词: Inflammatory bowel disease Pioglitazone Peroxisome proliferator?activated receptors NF?kappa B Transcription factor relA Trinitrobenzenesulfonic acid Sulfasalazine Cytoprotection Rats,sprague?dawley |
| 基金项目:河南省二〇一三科技发展计划( 132102310415) |
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| 摘要点击次数: 1957 |
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| 中文摘要: |
| 目的探讨吡格列酮对结肠炎保护作用及其可能机制。方法 SD大鼠采用随机数字表法分为对照组、模型组、柳氮磺吡啶( SASP)药物治疗组( SASP组)、吡格列酮低、中及高剂量治疗组(其中 SASP组与吡格列酮组为干预组)每组 8只。模型组及干预组经肛灌入 5%三硝基苯磺酸( TNBS)/乙醇 5 mL/kg，对照组灌入 0.85%氯化钠 5 mL/kg，造模后第 1天干，预组给予 SASP及不同剂量吡格列酮，对照组及模型组给予 0.85%氯化钠 10 mL/kg灌胃，统计炎症活动指数( DAI)、大体形态损伤指数(CMDI)、组织学损伤指数( TDI)的变化及免疫组织化学检测结肠过氧化物酶体增殖物激活受体 γ(PPAR?γ)及核因子 ?κB p65(NF?κB p65)的表达。结果(1)模型组、 SASP组、吡格列酮低、中、高剂量治疗组 DAI值分别为( 3.13±0.83)、(1.50±0.53)、(2.25±0.71)、(1.63±0.52)、(2.25±0.46)，SASP组、吡格列酮低、中、高剂量治疗组低于模型组， P值分别是 0.000、0.010、0.000、 0.010；吡格列酮低、中、高剂量治疗组与 SASP组比较， P值分别是 0.020、0.690、0.020；(2)模型组、 SASP组、吡格列酮低、中、高剂量治疗组 CMDI分别是( 2.63±0.52)、(1.13±0.83)、(1.38±0.52)、(1.13±0.83)、(1.63±0.84)SASP组、吡格列酮低、中、高剂量治疗组与模型组比较低于模型组， P值分别是 0.000、0.001、0.000、0.005。吡格列酮低、中、量治疗组与 SASP组比较， P值分别是 0.456、1.000、0.140；(3)模型组、 SASP组、吡格列酮低、中、高剂量治疗组 TDI分别是( 9.50±1.93)、(4.63±1.19)、(5.00± 高剂，1.31)、(4.75±1.04)、(4.00±0.76)，SASP组、吡格列酮低、中、高剂量治疗组与模型组比较，均 P＝0.000，吡格列酮低、中、高剂量治疗组与 SASP药物组比较， P值分别是 0.568、0.849、0.568；(4)对照组、模型组、 SASP组、吡格列酮低、中、高剂量治疗组 PPAR? γ值分别是( 46.62±3.07)、(27.24±2.71)、(39.79±1.39)、(34.62±2.26)、(40.13±2.23)、(36.22±2.11)。模型组表达低于对照组， P＝ 0.000；SASP组、吡格列酮低、中、高剂量治疗组 PPAR?γ表达高于模型组，均 P＝0.000，吡格列酮低、中、高剂量治疗组与 SASP组相比较， P值分别是 0.000、0.773、0.004；(5)对照组、模型组、 SASP组、吡格列酮低、中、高剂量治疗组 NF?κB p65值分别是(17.48±0.84)、(33.74±1.56)、(22.18±2.08)、(19.28±1.32)、(21.46±1.76)、(22.13±1.58)模型组表达高于对照组， P＝0.000；SASP组、吡格列酮低、中、高剂量治疗组表达低于模型组，均 P＝0.000。吡格列酮低、中、量治疗组与 SASP组相比较， P值分别是 0.001、0.370、0.952；(6)对照组、模型组、 SASP组、吡格列酮低、中高剂量治疗组 PPAR?γ与 NF?κB p65的表达均呈负相关，相关系数分别为 -0.851、-0.875、-0.771、-0.776、-0.766、-0.910，P值分别是 0.007、0.004、0.025、0.024、0.027、0.000。结论吡格列酮可有效改善 TNBS诱导的炎症性肠病大鼠的症状， DAI、CMDI及 TDI降低，而 PPAR?γ、NF?κB p65升高，其治疗效果与 SASP相近。其作用机制可能是吡格列酮作为 PPAR?γ的人工配体，通过增加 PPAR?γ的表达，抑制 NF?κB p65的表达，减轻结高剂，肠的炎症和免疫反应。 |
| 英文摘要: |
| Objective To discuss the function and mechanism of pioglitazone on inflammatory bowel disease.Methods SD rats were randomly assigned into the control group and the model group，the SASP drug treatment group(SASP group)，the low?dose pi? oglitazone treatment group，the pioglitazone medium?dose treatment group，and the pioglitazone high?dose treatment group(amongthem，SASP group and pioglitazone group were intervention group) with 8 in each group.The model group and the intervention group were perfused with 5% trinitrobenzene sulfonic acid(TNBS)/ethanol 5 mL/kg，and the control group was filled with 0.85% sodium chloride 5 mL/kg.On the first day after modeling，the intervention group was given SASP and different doses of pioglitazone. The model group was given 0.85% sodium chloride 10 mL/kg，and the changes of inflammatory activity index(DAI)，gross morpho? logical injury index(CMDI)，tissue damage index(TDI)were detected and the expression of Peroxidosome proliferators activate re? ceptor γ(PPAR?γ)and Nuclear factor κB p65(NF?κB p65)in colon was detected by immunohistochemistry.Results(1)The DAI values of the model group，SASP group and pioglitazone low，medium and high dose treatment groups were(3.13±0.83)，(1.50± 0.53)(2.25±0.71)(1.63±0.52)and(2.25±0.46)，respectively，and DAI values in SASP group，pioglitazone low，medium and high? dosetrea，tmentgroupw，ere lower than those in the model group(P＝0.000，0.010，0.000，and 0.010，respectively)； the low，medium， and high doses of pioglitazone were compared with the SASP group，and the P values were 0.020，0.690，and 0.020，respectively；(2)The CMDI of the model，the low，medium and high doses of the group，SASP group and pioglitazone were(2.63±0.52)，(1.13± 0.83)(1.38±0.52)(1.13±0.83)and(1.63±0.84)respectively，and CMDI in SASP group and the low，medium and high doses of pioglitaz，onewaslower，thanthatin，the model group(，P＝0.000，0.001，0.000，and 0.005，respectively).Compared with the SASP group，the low，medium and high doses of pioglitazone had a P value of 0.456，1.000，and 0.140，respectively.(3)The TDI of the model group，SASP group，and low，medium，and high doses of pioglitazone were(9.50±1.93)，(4.63±1.19)，(5.00±1.31)，(4.75± 1.04)and(4.00±0.76)，respectively.SASP group，pioglitazone low，medium and high dose treatment group compared with the mod? elgroup，(all P＝0.000)； pioglitazone low，medium and high dose treatment group compared with SASP drug group，the P values were 0.568，0.849，and 0.568，respectively.(4)The PPAR?γ values of the control group，model group，SASP group，and pioglitazone low，medium，and high dose treatment groups were(46.62±3.07)(27.24±2.71)(39.79±1.39)(34.62±2.26)，(40.13±2.23)and(36.22±2.11)， roup(all P＝0.000)； the SASP group and the low，medium and high doses of pioglitazone was higher than the model group(all P＝0.000)； low，medium and high doses of pioglitazone compared with SASP group，the P values were 0.000，0.773，and 0.004，respectively；(5)The NF?κB p65 val? ues of the control group，model group，SASP group，and pioglitazone low，medium，and high dose treatment groups were(17.48± respectively.Theexpressionofthemodelgroupwas，lowerthanthat，ofthecontrolg，0.84)(33.74±1.56)(22.18±2.08)(19.28±1.32)(21.46±1.76)and(22.13±1.58)，respectively，the expression of the model groupwa，shigherthant，hatofthecontro，lgroup(allP＝，0.000)； NF?κB p65 values of the low，medium and high doses of piogli? tazone，the SASP group were lower than those in the model group(all P＝0.000).Compared with the SASP group，the low，medi? um and high doses of pioglitazone had a P value of 0.001，0.370，and 0.952，respectively；(6)The expressions of PPAR?γ and NF? κB p65 in control group，model group，SASP group，low，middle and high dose of pioglitazone，were negatively correlated with corre? lation coefficients of -0.851，-0.875，-0.771，-0.776，-0.766 and -0.910，respectively，and P values of 0.007，0.004，0.025，0.024， 0.027and 0.000，respectively.Conclusions Pioglitazone can effectively improve the symptoms of TNBS?induced inflammatory bow? el disease in rats，decrease DAI，CMDI and TDI，and increase PPAR?γ and NF?κB p65 levels.Its therapeutic effect is similar tothat of SASP.The mechanism of action may be that pioglitazone acts as an artificial ligand for PPAR?γ，which inhibits the expres?sion of NF?κB p65 and increases the inflammation and immune response of the colon by increasing the expression of PPAR?γ. |
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