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Cell-permeable Tat-NBD peptide attenuates rat pancreatitis and acinus cell inflammation response

查看全文 作　　者：You-Ming [1]Long;Ken [2]Chen;Xue-Jin [3]Liu;Wen-Rui [4]Xie;Hui [5]Wang 高影响力作者 机构地区：[1]College of Medicine, Guangdong Pharmaceutical University, Guangzhou 510080, Guangdong Province, China;[2]Clinical and Pharmaceutical Research Unit,Guangdong Pharmaceutical University, Guangzhou 510310,Guangdong Province, China;[3]Department of Digestion, Zhoukou Central Hospital of Henan, Zhoukou 46600, Henan Province, China;[4]First Affiliated Hospital of Guangdong Pharmaceutical' University, Guangzhou 510080, Guangdong Province, China;[5]Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, China高影响力机构 出　　处：《World Journal of Gastroenterology》索引2009年第15卷第5期,共9页高影响力期刊 基　　金：Supported by The Natural Science Foundation, No. 04009624 摘　　要：AIM: To investigate the effects of Tat-NEMO-binding domain (NBD) peptide on taurocholate-induced pancreatitis and lipopolysaccharide (LPS)-stimulated AR42J acinus cells inflammatory response in rats. METHODS: Sodium taurocholate (5%) was used to induce the pancreatitis model. Forty-eight rats from the taurocholate group received an intravenous bolus of 13 mg/kg Tat-NBD (wild-type, WT) peptide, TatNBD (mutant-type, MT) peptide, NBD peptide or Tat peptide. The pancreatic histopathology was analyzed by hematoxylin staining. LPS was added to the culture medium to stimulate the AR42J cells. For pretreatment, cells were incubated with different peptides for 2 h before LPS stimulation. Expression of IL-1β and TNF-α mRNA was analyzed using a semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR) method. IL-1β and TNF-α protein in culture medium were detected by enzyme linked immunosorbent assay (ELISA). NF-κB DNA-binding in pancreas was examined by electrophoretic mobility shift assays. P65 expression of AR42J was determined by Strept Actividin-Biotin Complex (SABC) method. RESULTS: Pretreatment with Tat-NBD (WT) peptide at a concentration of 13 mg/kg body wt showed beneficial effect in pancreaitis model. LPS (10 mg/L) resulted in an increase of IL-1β mRNA, IL-1β protein, TNF-α mRNA and TNF-α protein, whereas signifi cantly inhibitory effects were observed when cells were incubated with Tat-NBD (WT). Consisting with p65 expression decrease analyzed by SABC method, NF-κB DNA-binding activity significantly decreased in Tat-NBD (WT) pretreatment group, especially at the largest dose. No significant changes were found in the control peptide group. CONCLUSION: Our result supports that active NF-κB participates in the pathogenesis of STC-induced acute pancreatitis in rats. Tat-NBD (WT) peptide has anti-inflammatory effects in this model and inhibits the inflammation of acinus simulated by LPS. 关 键 词：胰腺炎 组织病理学 胰腺疾病 诊断 治疗
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