Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing 210002, Jiangsu Province, China.
World J Gastroenterol. 2010 Jun 28;16(24):2994-3001. doi: 10.3748/wjg.v16.i24.2994.
To investigate the effect of emodin on expression of claudin-4, claudin-5 and occludin, as well as the alveolar epithelial barrier in rats with pancreatitis induced by sodium taurocholate.
Experimental pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Emodin was injected via the external jugular vein 3 h after induction of acute pancreatitis. Rats from sham operation group and acute pancreatitis group were injected with normal saline (an equivalent volume as emodin) at the same time point. Samples of lung and serum were obtained 6 h after drug administration. Pulmonary morphology was examined with HE staining. Pulmonary edema was estimated by measuring water content in lung tissue samples. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) level were measured by enzyme-linked immunospecific assay. Serum amylase and pulmonary myeloperoxidase (MPO) activity were detected by spectrophotometry. Alveolar epithelial barrier was assessed by pulmonary dye extravasation. Expression of claudin-4, claudin-5 and occludin in lung tissue samples was examined by immunohistology, quantitative real-time reverse transcription polymerase chain reaction and Western blotting analysis, respectively.
Pancreatitis-associated lung injury was characterized by pulmonary edema, leukocyte infiltration, alveolar collapse, and elevated serum amylase level. The pulmonary damage, pulmonary pathological scores, serum amylase and MPO activity, TNF-alpha and IL-6 levels, and wet/dry ratio were decreased in rats after treatment with emodin. Immunostaining of claudin-4, claudin-5 and occludin was detected in lung tissue samples from rats in sham operation group, which was distributed in alveolar epithelium, vascular endothelium, and bronchial epithelium, respectively. The mRNA and protein expression levels of claudin-4, claudin-5 and occludin in lung tissue samples were markedly decreased, the expression level of claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin.
Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis.
研究大黄素对胆酸钠诱导的胰腺炎大鼠中 Claudin-4、Claudin-5 和 Occludin 的表达以及肺泡上皮屏障的影响。
通过逆行注射 5%胆酸钠至胆胰管诱导实验性胰腺炎。在急性胰腺炎诱导后 3 小时通过颈外静脉注射大黄素。假手术组和急性胰腺炎组的大鼠同时注射生理盐水（与大黄素等体积）。给药后 6 小时获取肺和血清样本。通过 HE 染色检查肺形态。通过测量肺组织样本中的水分含量来估计肺水肿。通过酶联免疫吸附试验测定肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。通过分光光度法检测血清淀粉酶和肺髓过氧化物酶（MPO）活性。通过肺染料渗出评估肺泡上皮屏障。通过免疫组织化学、实时定量逆转录聚合酶链反应和 Western 印迹分析分别检测肺组织样本中 Claudin-4、Claudin-5 和 Occludin 的表达。
胰腺炎相关的肺损伤表现为肺水肿、白细胞浸润、肺泡塌陷和血清淀粉酶水平升高。与未治疗的急性胰腺炎大鼠相比，大黄素治疗后大鼠的肺损伤、肺病理评分、血清淀粉酶和 MPO 活性、TNF-α和 IL-6 水平以及湿/干比均降低。Claudin-4、Claudin-5 和 Occludin 的免疫染色在假手术组大鼠的肺组织样本中检测到，分别分布在肺泡上皮、血管内皮和支气管上皮。与急性胰腺炎大鼠的肺组织样本相比，经大黄素治疗后，Claudin-4、Claudin-5 和 Occludin 的 mRNA 和蛋白表达水平明显降低，Claudin-4、Claudin-5 和 Occludin 的表达水平升高，肺组织样本中的肺染料渗出减少。
大黄素减轻了胰腺炎大鼠的肺水肿和炎症，增强了肺泡上皮屏障功能，并促进了急性胰腺炎大鼠肺组织样本中 Claudin-4、Claudin-5 和 Occludin 的表达。
