目的基于沉默信息调节因子3(SIRT3)/β-连环蛋白(β-catenin)/过氧化物酶体增殖物激活受体(PPARγ)信号通路探讨芪参益气滴丸治疗急性心肌梗死(AMI)模型大鼠的作用机制。方法雄性SD大鼠随机分为正常组、模型组、阿司匹林组、芪参益气滴...目的基于沉默信息调节因子3(SIRT3)/β-连环蛋白(β-catenin)/过氧化物酶体增殖物激活受体(PPARγ)信号通路探讨芪参益气滴丸治疗急性心肌梗死(AMI)模型大鼠的作用机制。方法雄性SD大鼠随机分为正常组、模型组、阿司匹林组、芪参益气滴丸组。建立AMI模型术后48h,各组给予相应的治疗处理。观察各组左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室质量指数(LVMI)、微血管密度(MVD),检测各组白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、核因子-B(NF-κB)、SIRT3、β-catenin、PPARγ m RNA的表达水平。结果与正常组相比,模型组LVEF、LVFS显著下降(均P<0.01),LVMI显著增高(P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组LVEF、LVFS显著增高(均P<0.01),LVMI显著下降(P<0.01);与阿司匹林组相比,芪参益气滴丸组LVEF、LVFS均显著增高(均P<0.01),LVMI显著下降(P<0.05)。与正常组相比,模型组MVD显著增高(P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组MVD显著增高(P<0.01);与阿司匹林组相比,芪参益气滴丸组MVD显著增高(P<0.01)。与正常组相比,模型组IL-6、TNF-α、NF-κB显著增高(均P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组IL-6、TNF-α、NF-κB显著下降(均P<0.01);与阿司匹林组相比,芪参益气滴丸组IL-6、TNF-α、NF-κB显著下降(均P<0.01)。与正常组相比,模型组SIRT3、β-catenin、PPARγ m RNA表达显著升高(均P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组SIRT3、β-cateninm RNA显著增高,PPARγ m RNA显著下降(均P<0.01)。与阿司匹林组相比,芪参益气滴丸组SIRT3、β-cateninm RNA显著增高,PPARγ m RNA显著下降(均P<0.01)。结论芪参益气滴丸可能通过调节SIRT3/β-catenin/PPARγ信号通路改善AMI大鼠心室重构,降低炎症反应,促进血管新生。展开更多
This study examined if the anti-tumorigenesis effect of Exendin-4 in HT29 and HCT116 colorectal cancer(CRC)involves modulation of SIRT1 and Akt/GSR3K/β-catenin/NF-κB axis.HT29 and HCT116 cells were treated either wi...This study examined if the anti-tumorigenesis effect of Exendin-4 in HT29 and HCT116 colorectal cancer(CRC)involves modulation of SIRT1 and Akt/GSR3K/β-catenin/NF-κB axis.HT29 and HCT116 cells were treated either with increasing levels of Exendin-4(0.0-200μM)or with Exendin-4(at its IC50)in the presence or absence of EX-527(10μM/a selective SIRT1 inhibitor)or Exendin-4(9-39)amide(E(9-39)A)(1μM/an Exendin-4 antagonist).In a dose-dependent manner,Exendin-4 inhibited cell survival,but enhanced levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA)in both HT29 and HCT116.In both cell lines and at it has an IC50(45μM for HT29 and 35μM for HCT1165),Exendin-4 also significantly reduced cell survival,migration,and invasion of both cell types,with no effect on the expression GLP-1 receptors(GLPRs)nor of the activity of Akt.At these doses,Exendin-4 also increased the expression of SIRT1 but reduced the acetylation of NF-κB and the expression of Bax and cleaved caspase-3 and in both cell lines.Concomitantly,protein levels of p-GS3Kβ(Ser9),total and acetylatedβ-catenin,and Anix2 were significantly decreased,but levels of p-GS3Kβ(Ser9)and p-β-catenin(Ser33/37/Thr41)were significantly increased in both HT29 and HCT116-exendin-4 treated cells.All the effects exerted by Exendin-4 were completely prevented by Ex527 or E(9-39)A.In conclusion,Exendin-4 suppresses the tumorigenesis of HT29 and HCT116 CRC cell activation of GS3Kβ-induced inhibition ofβ-catenin and NF-κβin a SIRT1-dependent mechanism.展开更多
文摘目的基于沉默信息调节因子3(SIRT3)/β-连环蛋白(β-catenin)/过氧化物酶体增殖物激活受体(PPARγ)信号通路探讨芪参益气滴丸治疗急性心肌梗死(AMI)模型大鼠的作用机制。方法雄性SD大鼠随机分为正常组、模型组、阿司匹林组、芪参益气滴丸组。建立AMI模型术后48h,各组给予相应的治疗处理。观察各组左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室质量指数(LVMI)、微血管密度(MVD),检测各组白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、核因子-B(NF-κB)、SIRT3、β-catenin、PPARγ m RNA的表达水平。结果与正常组相比,模型组LVEF、LVFS显著下降(均P<0.01),LVMI显著增高(P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组LVEF、LVFS显著增高(均P<0.01),LVMI显著下降(P<0.01);与阿司匹林组相比,芪参益气滴丸组LVEF、LVFS均显著增高(均P<0.01),LVMI显著下降(P<0.05)。与正常组相比,模型组MVD显著增高(P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组MVD显著增高(P<0.01);与阿司匹林组相比,芪参益气滴丸组MVD显著增高(P<0.01)。与正常组相比,模型组IL-6、TNF-α、NF-κB显著增高(均P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组IL-6、TNF-α、NF-κB显著下降(均P<0.01);与阿司匹林组相比,芪参益气滴丸组IL-6、TNF-α、NF-κB显著下降(均P<0.01)。与正常组相比,模型组SIRT3、β-catenin、PPARγ m RNA表达显著升高(均P<0.01);与模型组相比,阿司匹林组、芪参益气滴丸组SIRT3、β-cateninm RNA显著增高,PPARγ m RNA显著下降(均P<0.01)。与阿司匹林组相比,芪参益气滴丸组SIRT3、β-cateninm RNA显著增高,PPARγ m RNA显著下降(均P<0.01)。结论芪参益气滴丸可能通过调节SIRT3/β-catenin/PPARγ信号通路改善AMI大鼠心室重构,降低炎症反应,促进血管新生。
基金the deanship of Scientific Research at King Khalid University,Abha,KSA for supporting this work under grant number(R.G.P.2/80/41)the work was supported by the Taif University Researchers Supporting Project Number(TURSP-2020/99)Taif University,Taif,Saudi Arabia and this work was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program.
文摘This study examined if the anti-tumorigenesis effect of Exendin-4 in HT29 and HCT116 colorectal cancer(CRC)involves modulation of SIRT1 and Akt/GSR3K/β-catenin/NF-κB axis.HT29 and HCT116 cells were treated either with increasing levels of Exendin-4(0.0-200μM)or with Exendin-4(at its IC50)in the presence or absence of EX-527(10μM/a selective SIRT1 inhibitor)or Exendin-4(9-39)amide(E(9-39)A)(1μM/an Exendin-4 antagonist).In a dose-dependent manner,Exendin-4 inhibited cell survival,but enhanced levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA)in both HT29 and HCT116.In both cell lines and at it has an IC50(45μM for HT29 and 35μM for HCT1165),Exendin-4 also significantly reduced cell survival,migration,and invasion of both cell types,with no effect on the expression GLP-1 receptors(GLPRs)nor of the activity of Akt.At these doses,Exendin-4 also increased the expression of SIRT1 but reduced the acetylation of NF-κB and the expression of Bax and cleaved caspase-3 and in both cell lines.Concomitantly,protein levels of p-GS3Kβ(Ser9),total and acetylatedβ-catenin,and Anix2 were significantly decreased,but levels of p-GS3Kβ(Ser9)and p-β-catenin(Ser33/37/Thr41)were significantly increased in both HT29 and HCT116-exendin-4 treated cells.All the effects exerted by Exendin-4 were completely prevented by Ex527 or E(9-39)A.In conclusion,Exendin-4 suppresses the tumorigenesis of HT29 and HCT116 CRC cell activation of GS3Kβ-induced inhibition ofβ-catenin and NF-κβin a SIRT1-dependent mechanism.
