抗生素敲减肠道菌群对由雨蛙素诱导的小鼠慢性胰腺炎的影响
首发时间:2019-02-21
摘要:目的探讨抗生素(Abx)敲减肠道菌群后对雨蛙素诱导的慢性胰腺炎(CP)小鼠的影响及其机制。方法将8周龄SPF级C57BL/6J雄性小鼠随机分成正常对照组(Control组)、短链脂肪酸对照组(SCFA组)、模型对照组(Cae组)、抗生素处理组(Cae+Abx组)、短链脂肪酸治疗组(Cae+Abx+SCFA组),造模前连续7天灌胃Abx并持续至造模结束,随后连续四周腹腔注射雨蛙素建立小鼠CP模型。采用商业试剂盒进行马松三色染色检测纤维化程度;采用实时荧光定量PCR法(qPCR)测定胰腺组织中炎症因子和生长因子水平;采用蛋白质免疫印迹法(Western blot)测定胰腺组织中组蛋白去乙酰化酶(HDACs)和纤维化相关蛋白的表达。结果Abx能够加重由雨蛙素诱导的小鼠慢性胰腺炎,表现为胰腺萎缩加重,腺泡细胞损失增加,纤维化相关蛋白表达上升,促进Smad3通路激活,减少结肠短链脂肪酸(SCFAs)含量,上调胰腺中HDAC1表达。Abx敲减肠道菌群后加重小鼠CP,其作用机制与肠道代谢物SCFAs的减少和HDACs有关。
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The effects of reduction of intestinal flora by antibiotics to cerulein-induced chronic pancreatitis in mice
Abstract:Objective: To investigate the effects of reduction of intestinal flora by antibiotics (Abx) on cerulein-induced chronic pancreatitis(CP) and its possible mechanism in mice. Methods: 8 weeks male C57BL/6J mice were randomly divided into control group, SCFA control group model control group, antibiotic treatment group and SCFA treatment group. Antibiotics were administered intragastrically for 7 days before modeling and throughout the model, then CP model was established by intraperitoneal injection of cerulein for 4 weeks. The level of fibrosis was determined by masson trichrome stain kits, and the levels of inflammatory factors and growth factors were tested by real-time polymerase chain reaction(qPCR). Histone deacetylases(HDACs) and fibrosis-related proteins were detected by Western blotting. Results: Abx can worsen the cerulein-induced CP in mice, which is characterized by increased pancreatic atrophy, loss of acinar cells and increased fibrosis-related proteins, as well as the activation of Smad3 pathway, reduction of intestinal short chain fatty acids(SCFAs), and up-regulated the expression of HDAC1 in pancreas. Conclusion: Reduction of intestinal flora by Abx can aggravate CP in mice and its mechanism may be related to the decrease of SCFAs and the expression of HDACs.
Keywords: chronic pancreatitis fibrosis short chain fatty acids histone deacetylase
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抗生素敲减肠道菌群对由雨蛙素诱导的小鼠慢性胰腺炎的影响
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