Intervention effect of emodin on pancreatic acinar cell apoptosis in severe acute pancreatitis rats
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摘要: 目的 探讨大黄素对重症急性胰腺炎大鼠胰腺组织细胞凋亡的干预作用及机制。 方法 采用逆行胰胆管注射牛磺胆酸法进行造模,模型大鼠随机分入对照组、大黄素低剂量组、大黄素中剂量组和大黄素高剂量组;各组再随机编入3 h、6 h、12 h和24 h等4个时相点进行标本留置。检测血清淀粉酶、血清总钙和胰腺组织病理评分;应用DNA断裂的原位末端标记(TUNEL)法测定细胞凋亡并计算凋亡指数,免疫印迹法检测胰腺组织Notch-1、Hes-1和Hes-5蛋白表达情况。 结果 大黄素治疗组的血清淀粉酶均较模型对照组显著降低(P<0.01),血清总钙水平则均较模型对照组显著增高(P<0.05)。大黄素中剂量组和高剂量组胰腺病理评分均较模型对照组明显改善(P<0.01),高剂量组改善最显著。治疗各组的胰腺细胞凋亡指数在不同时间点均较模型对照组有不同程度升高,高剂量组效果最显著,低剂量组与模型对照组差异无统计学意义(P>0.05)。治疗各组的Notch-1蛋白表达量均较模型对照组增加,中剂量组和高剂量组效果相对显著(P<0.05)。大黄素高剂量组Hes-1蛋白表达量显著高于模型对照组(P<0.05)、低剂量组(P<0.05)和中剂量组(P<0.05)。大黄素中剂量组和高剂量组Hes-5蛋白表达量均显著高于模型对照组(P<0.05),且高剂量组蛋白表达量较低剂量组显著增加(P<0.05)。 结论 SAP时大黄素可以通过促进胰腺局部细胞凋亡而减轻胰腺炎反应,Notch-1/Hes信号通路是大黄素调控胰腺局部细胞凋亡的重要途径。Abstract: Objective To investigate the intervention effect of emodin on cell apoptosis in severe acute pancreatitis rats. Methods Models were induced by retrograde injection of taurocholic acid into pancreatic duct of rats.Then all the models were randomly divided into 4 groups,including control,low dose(10 mg/kg emodin),middle dose(20 mg/kg emodin) and high dose group(40 mg/kg emodin).Specimens of each group were taken at 3 h,6 h,12 h and 24 h randomly.Serum amylase,serum total calcium and pancreatic histopathologic score were measured.TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) staining was applied to measure apoptosis and apoptotic index.The protein expressions of Notch-1,Hes-1and Hes-5 were detected by Western blot. Results Compared with the control group,the serum amylase of emodin treatment groups were significantly lower(P<0.01).The serum total calcium levels in each treatment group were significantly higher than those in the control group (P<0.01),The pancreatic histopathologic scores of middle dose group and high dose group were significantly improved compared with control group(P<0.01),especially in high dose group.The apoptosis index of pancreatic cells in each treatment group points was higher than control group at different time,especially in high dose group,but the index was similar between low dose group and control group(P>0.05).The Notch-1 expression of treatment groups were higher than that of control group,and more significant in middle dose group and high dose group(P<0.01).The Hes-1 expression of high dose group was significantly higher than that of control group(P<0.05),low dose group(P<0.05) and middle dose group(P<0.05).The Hes-5 expression of middle dose group and high dose group was significantly higher than that of control group,and the Hes-5 expression of high dose group was significantly higher than that of low dose group(P<0.05). Conclusion Emodin can alleviate pancreatitis by promoting apoptosis of local pancreatic cells when severe acute pancreatitis occurs.Notch-1/Hes signaling pathway is an important pathway for emodin regulating pancreatic acinar cell apoptosis.
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Key words:
- Severe acute pancreatitis /
- Emodin /
- Cell apoptosis /
- Signal transduction
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