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MiR-320通过调节JAK2/STAT3和NF-κB信号通路对急性胰腺炎大鼠肠道损伤的影响
Effect of Mi R-320 on Intestinal Injury in Rats With Acute Pancreatitis by Regulating JAK2/STAT3 and NF-κB Signaling Pathways
【摘要】 背景:微RNA-320(mi R-320)表达在急性胰腺炎中下调,对急性胰腺炎的影响机制尚不完全清楚。目的:探讨mi R-320对急性胰腺炎大鼠肠道损伤的影响及其机制。方法:将大鼠随机分为假手术组、模型组、mi R-320激动剂组(agomir mi R-320组)、mi R-320激动剂对照组(agomir NC组)、JAK2抑制剂组(AG490组)、NF-κB通路抑制剂组(PDTC组),采用逆行胰胆管注射5%牛磺胆酸钠法制备急性胰腺炎大鼠模型。全自动生化分析仪检测血清淀粉酶、脂肪酶水平,ELISA法检测血清TNF-α、IL-1β水平,HE染色观察大鼠胰腺和回肠组织病理变化,TUNEL染色法观察大鼠回肠组织细胞凋亡;实时荧光定量PCR(RT-q PCR)检测回肠组织mi R-320表达,蛋白质印迹法检测回肠组织JAK2/STAT3和NF-κB信号通路相关蛋白表达。结果:与假手术组相比,模型组大鼠胰腺和回肠损伤严重,病理学评分和回肠组织细胞凋亡率明显增加(P<0.05),血清淀粉酶、脂肪酶、TNF-α、IL-1β水平明显升高(P<0.05),回肠组织mi R-320表达明显降低(P<0.05),回肠组织p-JAK2/JAK2、p-STAT3/STAT3、p-p65/p65、p-IκBα/IκBα比值明显升高(P<0.05);与模型组相比,agomir mi R-320组、AG490组、PDTC组大鼠胰腺和回肠病理损伤减轻,病理学评分和回肠组织细胞凋亡率明显降低(P<0.05),血清淀粉酶、脂肪酶、TNF-α、IL-1β水平明显降低(P<0.05),回肠组织mi R-320表达明显升高(P<0.05),回肠组织p-JAK2/JAK2、p-STAT3/STAT3、p-p65/p65、p-IκBα/IκBα比值明显降低(P<0.05)。结论:Mi R-320可通过抑制JAK2/STAT3和NF-κB信号通路的激活改善急性胰腺炎大鼠肠道损伤。
【Abstract】 Background: Expression of micro RNA-320(mi R-320) is down regulated in acute pancreatitis, and the mechanism of its effect on acute pancreatitis is still unclear. Aims: To investigate the effect of mi R-320 on intestinal injury in rats with acute pancreatitis and its mechanism. Methods: Rats were randomly divided into sham operation group, model group, mi R-320 agonist group(agomir mi R-320 group), mi R-320 agonist control group(agomir NC group), JAK2 inhibitor group(AG490 group), and NF-κB pathway inhibitor group(PDTC group). The rat model of acute pancreatitis was established by retrograde injection of 5% sodium taurocholate to the bile duct. The automatic biochemical analyzer was used to detect serum levels of amylase and lipase; ELISA assay was used to detect serum levels of TNF-α and IL-1β; HE staining was used to observe the pathological changes of rat pancreas and ileum; TUNEL staining was used to observe cell apoptosis in rat ileum; real-time fluorescent quantitative PCR(RT-q PCR) was used to detect the expression of mi R-320 in ileum tissue; Western blotting method was used to detect the expressions of JAK2/STAT3 and NF-κB signaling pathway related proteins in ileum. Results: Compared with sham operation group, the pancreas and ileum were severely injured in model group, and the pathological score and ileum cell apoptosis were significantly increased(P<0.05), serum levels of amylase, lipase, TNF-α, and IL-1β were significantly increased(P<0.05), the expression of mi R-320 in ileum tissue was significantly decreased(P<0.05), the ratios of p-JAK2/JAK2, p-STAT3/STAT3, p-p65/p65, and p-IκBα/IκBα in ileum tissue were significantly increased(P<0.05). Compared with model group, the pathological damages of pancreas and ileum in agomir mi R-320 group, AG490 group and PDTC group were reduced, and the pathological score and ileum cell apoptosis were significantly decreased(P<0.05), serum levels of amylase, lipase, TNF-α, and IL-1β were significantly decreased(P<0.05), the expression of mi R-320 in ileum tissue was significantly increased(P<0.05), the ratios of p-JAK2/JAK2, p-STAT3/STAT3, p-p65/p65, and p-IκBα/IκBα in ileum tissue were significantly decreased(P<0.05). Conclusions: Mi R-320 can improve the intestinal injury in rats with acute pancreatitis by inhibiting the activation of JAK2/STAT3 and NF-κB signaling pathways.
【Key words】 MicroRNA-320; Acute Pancreatitis; JAK2/STAT3; NF-κB; Intestinal Injury;
- 【文献出处】 胃肠病学 ,Chinese Journal of Gastroenterology , 编辑部邮箱 ,2022年10期
- 【分类号】R576
- 【下载频次】5