解玉杰.基于SIRT1/FOXO1通路探讨茶多酚对急性胰腺炎肺损伤大鼠的保护作用[J].内科急危重症杂志,2020,26(3):226-230
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| DOI：10.11768/nkjwzzzz20200313 |
| 中文关键词: SIRT1/FOXO1通路 急性胰腺炎 茶多酚 肺损伤 尼克酰胺 |
| 英文关键词: |
| 基金项目:莱芜市科学技术项目资助[No:2013 3 334（1） 5];山东省中医药科技发展计划项目（No:2019-0640) |
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| 中文摘要: |
| 目的：基于SIRT1/FOXO1通路探讨茶多酚（TP）对急性胰腺炎(AP)肺损伤大鼠的保护作用。方法：选取60只SD大鼠，随机分为假手术组、模型组、TP（100mg/kg）组、SIRT1抑制剂尼克酰胺（NA组，100mg/kg）组、TP+尼克酰胺组（TP+NA组，TP、NA均为100mg/kg），每组12只。采用逆行胆胰管注射5%牛磺胆酸钠（1mL/kg）建立AP肺损伤大鼠模型，给药5d后处死大鼠，测量腹水量，肺组织干、湿质量，计算干湿重比值（W/D）。苏木精-伊红染色（HE）观察各组大鼠肺组织病理情况，进行Holfbauer评分。采用全自动血气分析仪检测血氧分压(PaO2)、二氧化碳分压(PaCO2)、氧合指数(OI)等指标。用酶联免疫吸附法（ELISA）试剂盒检测大鼠血清肿瘤坏死因子α（TNF-α）、白介素6（IL-6）及淀粉酶水平，蛋白免疫印迹法检测SIRT1、FOXO1及acely-FOXO1蛋白表达。结果：与假手术组比较，模型组大鼠腹水量、肺组织W/D、Holfbauer评分、血PaCO2、TNF-α、IL-6、淀粉酶水平及acely-FOXO1蛋白表达显著升高，PaO2、OI及SIRT1蛋白表达显著降低（均P＜0.05）。与模型组比较，TP组大鼠腹水量、肺组织W/D、Holfbauer评分、血PaCO2、TNF-α、IL-6、淀粉酶水平及acely-FOXO1蛋白表达降低，PaO2、OI及SIRT1蛋白表达升高（均P＜0.05），而NA组大鼠腹水量、肺组织W/D、Holfbauer评分、血PaCO2、TNF-α、IL-6、淀粉酶水平及acely-FOXO1蛋白表达升高，PaO2、OI、SIRT1蛋白表达降低（均P＜0.05）。与TP+NA组比较，NA组大鼠腹水量、肺组织W/D、Holfbauer评分、血PaCO2、TNF-α、IL-6、淀粉酶水平及acely-FOXO1蛋白表达升高，PaO2、OI、SIRT1蛋白表达降低（均P＜0.05），而TP组大鼠腹水量、肺组织W/D、Holfbauer评分、血PaCO2、TNF-α、IL-6、淀粉酶水平及acely-FOXO1蛋白表达降低，PaO2、OI、SIRT1蛋白表达升高（均P＜0.05）。各组大鼠FOXO1蛋白表达差异无统计学意义（P＞0.05）。结论：TP可能通过上调SIRT1/FOXO1信号，改善AP肺损伤大鼠的肺组织损伤。 |
| 英文摘要: |
| Objective: To investigate the protective effect of tea polyphenols (TP) on lung injury induced by acute pancreatitis in rats based on SIRT1/FOXO1 pathway. Methods: Sixty SD rats were randomly divided into sham operation group, model group, TP group (100mg/kg TP), SIRT1 inhibitor nicotinamide (NA group, 100mg/kg nicotinamide) and TP + NA group (100mg/kg of TP and NA respectively), with 12 rats in each group. The rat models of acute pancreatitis with lung injury was established by retrograde injection of 5% sodium taurocholate (1mL/kg). The rats were killed 5 days after administration. The ascites volume, dry and wet masses of lung tissue were measured, and the ratio of dry to wet weight (W/D) was calculated. The hematoxylin eosin (HE) staining was used to observe the pathological changes of lung in rats of each group. The Holfbauer score was recorded, and blood gas index \[PaO2, PaCO2, oxygenation index (OI) = PaO2/FiO2) was detected by automatic blood gas analysis. The levels of serum TNF α, IL 6 and amylase in rats were determined by ELISA kit. Western blotting was used to detect the expressions of SIRT1, FOXO1 and acely FOXO1. Results: Compared with sham operation group, the ascites volume, W/D ratio, Holfbauer score, PaCO2, levels of TNF α, IL 6 and amylase, acely FOXO1 protein expression were significantly increased, and the expressions of PaO2, OI and SIRT1 decreased significantly in the model group (all P<0.05). Compared with the model group, the ascites volume, W/D ratio, Holfbauer score, PaCO2, 〖LM〗levels of TNF α, IL 6 and amylase, acely FOXO1 protein expression were significantly decreased, the expressions of PaO2, OI and SIRT1 increased significantly in the TP group (all P<0.05); but the ascites volume, W/D, Holfbauer score, PaCO2, levels of TNF α, IL 6 and amylase, acely FOXO1 protein expression were significantly increased, and the expressions of PaO2, OI and SIRT1 decreased significantly in the NA group (P<0.05). Compared with TP+NA group, the ascites volume, W/D ratio, Holfbauer score, PaCO2, levels of TNF α, IL 6 and amylase, acely FOXO1 protein expression were significantly increased, the expressions of PaO2, OI and SIRT1 decreased significantly in NA group (all P<0.05); but the ascites volume, W/D ratio, Holfbauer score, PaCO2, levels of TNF α, IL 6 and amylase, acely FOXO1 protein expression were significantly decreased, and the expressions of PaO2, OI and SIRT1 increased significantly in TP group (all P<0.05). There was no significant change in FOXO1 protein expression in all groups (P>0.05). Conclusion: TP can protect lung tissue of rats with acute pancreatitis and lung injury, possibly by up regulating SIRT1/FOXO1 signalpathway. |
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