文章摘要
杨根华,李夏西,董 玲,徐春玲,凌 琳,刘清华.双歧杆菌调节VIP/cAMP/PKA和mTOR通路改善溃疡性结肠炎小鼠的实验研究[J].,2022,(20):3840-3847
双歧杆菌调节VIP/cAMP/PKA和mTOR通路改善溃疡性结肠炎小鼠的实验研究
Bifidobacterium Ameliorates Ulcerative Colitis in Mice by Modulating VIP/cAMP/PKA and mTOR Pathways
投稿时间:2022-06-20  修订日期:2022-07-18
DOI:10.13241/j.cnki.pmb.2022.20.008
中文关键词: 双歧杆菌  VIP/cAMP/PKA通路  mTOR通路  溃疡性结肠炎
英文关键词: Bifidobacterium  VIP/cAMP/PKA pathway  mTOR pathway  Ulcerative colitis
基金项目:国家自然科学基金青年项目(81800503);深圳宝安区医疗卫生基础研究项目(2020JD286);深圳宝安区医疗卫生基础研究项目(2018JD209)
作者单位E-mail
杨根华 南方医科大学深圳医院消化内科 广东 深圳 518000 yang_genhua@163.com 
李夏西 南方医科大学深圳医院消化内科 广东 深圳 518000  
董 玲 南方医科大学深圳医院消化内科 广东 深圳 518000  
徐春玲 南方医科大学深圳医院消化内科 广东 深圳 518000  
凌 琳 南方医科大学深圳医院消化内科 广东 深圳 518000  
刘清华 南方医科大学深圳医院消化内科 广东 深圳 518000  
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中文摘要:
      摘要 目的:探讨双歧杆菌MIMBb75通过调节血管活性肠肽(VIP)/环磷酸腺苷(cAMP)/蛋白激酶A(PKA)和哺乳动物雷帕霉素靶蛋白(mTOR)通路对溃疡性结肠炎(UC)小鼠的影响。方法:BALB/c小鼠随机分为正常对照(NC)组、结肠炎模型(UC)组、Mesalazine组和MIMBb75低、高剂量组、MIMBb75高剂量+VIP antagonist组、MIMBb75高剂量+MHY1485组(每组10只),除NC组外均采用5%葡聚糖硫酸钠(DSS)诱导UC模型。治疗结束后,观察小鼠的一般情况及UC疾病活动指数(DAI),检测小鼠肠道组织病理损伤、结肠组织中髓过氧化物酶(MPO)活性、肠道菌群多样性(Chao指数、Shannon指数和Simpson指数)及结肠组织VIP、cAMP、PKA、水通道蛋白3(AQP3)、mTOR、核糖体蛋白S6激酶(S6K1)的mRNA和蛋白水平。结果:与UC组相比,MIMBb75低、高剂量组和Mesalazine组小鼠的体重升高、DAI评分降低,组织病理损伤得到改善,结肠长度增加,MPO活性降低,Chao指数、Shannon指数和Simpson指数升高;VIP、cAMP、PKA、AQP3的mRNA水平和VIP、cAMP、AQP3蛋白的表达及PKA的磷酸化水平升高,mTOR和S6K1 mRNA及其蛋白的磷酸化水平降低(P<0.05)。与MIMBb75高剂量组相比,MIMBb75高剂量+VIP antagonist组VIP、cAMP、PKA、AQP3的mRNA水平和VIP、cAMP、AQP3蛋白的表达及PKA的磷酸化水平降低(P<0.05);MIMBb75高剂量+MHY1485组mTOR和S6K1 mRNA及其蛋白的磷酸化水平升高(P<0.05)。VIP antagonist和MHY1485均能逆转MIMBb75对UC小鼠的保护作用,使其结肠损伤加重,MPO活性增高(P<0.05)。结论:双歧杆菌可改善UC小鼠的结肠损伤,增加肠道菌群的多样性,这可能与激活VIP/cAMP/PKA通路、抑制mTOR通路有关。
英文摘要:
      ABSTRACT Objective: To investigate the impact of Bifidobacterium MIMBb75 on ulcerative colitis(UC) mice by regulating vasoactive intestinal peptide (VIP)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and mammalian target of rapamycin (mTOR) pathways. Methods: BALB/c mice were randomly separated into normal control (NC) group, colitis model (UC) group, Mesalazine group, MIMBb75 low and high dose groups, MIMBb75 high dose combined VIP antagonist group, and MIMBb75 high dose combined MHY1485 group (10 per group), except for the NC group, 5% dextran sodium sulfate (DSS) was applied to induce the UC model. After the treatment, the general condition and UC disease activity index (DAI) of the mice were observed, and then pathological injury of intestinal tissues, myeloperoxidase (MPO) activity in colon tissue, intestinal microflora diversity (Chao index, Shannon index and Simpson index), VIP, cAMP, PKA and the mRNA and protein levels of VIP, cAMP, PKA, aquaporin 3 (AQP3), mTOR, ribosomal protein S6 kinase (S6K1) in colon tissue were detected. Results: Compared with UC group, the weight of mice increased, DAI score decreased, histopathological injury improved, colon length increased, MPO activity decreased, and Chao index, Shannon index and Simpson index increased in MIMBb75 low-dose group, high-dose group and Mesalazine group, the mRNA levels of VIP, cAMP, PKA, AQP3, the expression of VIP, cAMP and AQP3 protein and the phosphorylation level of PKA increased, while the phosphorylation levels of mTOR and S6K1 mRNA and protein decreased (P<0.05). Compared with mimb75 high dose group, the mRNA levels of VIP, cAMP, PKA and AQP3 and the expression of VIP, cAMP and AQP3 protein and the phosphorylation level of PKA in MIMBb75 high dose combine VIP antigonist group decreased (P<0.05). The phosphorylation levels of mTOR and S6K1 mRNA and protein increased in MIMBb75 high dose combine MHY1485 group (P<0.05). VIP antigonist and MHY1485 could reverse the protective effect of MIMBb7 on UC mice, aggravate the colonic injury and increase the MPO activity (P<0.05). Conclusion: Bifidobacterium can improve colon damage and increase the diversity of intestinal flora in UC mice, which may be related to activation of VIP/cAMP/PKA pathway and inhibition of mTOR pathway.
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