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Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis.
J Dig Dis. 2009 Feb; 10(1):30-40.JD

Abstract

OBJECTIVE

To study the effects of gut-derived endotoxin translocation and NF-kappaB activation on the aggravating mechanism of severe acute pancreatitis (SAP) and of treatment with pyrrolidine dithiocarbamate (PDTC) on rats with SAP.

METHODS

SD rats were randomly divided into sham operation group (SO), SAP group, SAP + lipopolysaccharide(LPS) group, pyrrolidine dithiocarbamate (PDTC) treatment group and LPS group. Biochemical parameters and cytokines were examined in the serum. Multiple organs pathological slices were examined. Expression of NF-kappaB mRNA in the liver tissue was detected by RT-PCR. Activation of NF-kappaB by the method of streptomycin avidin-peroxidase (SP) and expression of NF-kappaB p65 protein and its binding activity were analyzed by Western blot and electrophoretic mobidity shift assay (EMSA).

RESULTS

Compared with sham operation group, the concentration of TNF-alpha, alanine aminotransferase (ALT), and diamine oxidase (DAO) in serum significantly increased in SAP + LPS group (P < 0.05). Pathological changes were markedly observed in tissues and the expression of NF-kappaB mRNA in the liver significantly increased (P < 0.05) also, the activation of NF-kappaB and binding activity of NF-kappaB p65 protein in the liver markedly increased (P < 0.01) in SAP + LPS group. Treatment with PDTC markedly reduced concentration of ALT, DAO and TNF-alpha, and the expression of NF-kappaB, and the pathologic scores, as well as significantly decreased the expression of NF-kappaB p65 protein.

CONCLUSION

The activation and overexpression of NF-kappaB may participate in the aggravating mechanism of SAP. Treatment with PDTC has a protective effect on multiple organs damage in SAP.

Authors+Show Affiliations

Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19236545

Citation

Wang, Yi Lin, et al. "Effects of Gut Barrier Dysfunction and NF-kappaB Activation On Aggravating Mechanism of Severe Acute Pancreatitis." Journal of Digestive Diseases, vol. 10, no. 1, 2009, pp. 30-40.
Wang YL, Zheng YJ, Zhang ZP, et al. Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis. J Dig Dis. 2009;10(1):30-40.
Wang, Y. L., Zheng, Y. J., Zhang, Z. P., Su, J. Y., Lei, R. Q., Tang, Y. Q., & Zhang, S. D. (2009). Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis. Journal of Digestive Diseases, 10(1), 30-40. https://doi.org/10.1111/j.1751-2980.2008.00360.x
Wang YL, et al. Effects of Gut Barrier Dysfunction and NF-kappaB Activation On Aggravating Mechanism of Severe Acute Pancreatitis. J Dig Dis. 2009;10(1):30-40. PubMed PMID: 19236545.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis. AU - Wang,Yi Lin, AU - Zheng,Yun Jiang, AU - Zhang,Zi Ping, AU - Su,Jing Ying, AU - Lei,Ruo Qing, AU - Tang,Yao Qing, AU - Zhang,Sheng Dao, PY - 2009/2/25/entrez PY - 2009/2/25/pubmed PY - 2009/7/9/medline SP - 30 EP - 40 JF - Journal of digestive diseases JO - J Dig Dis VL - 10 IS - 1 N2 - OBJECTIVE: To study the effects of gut-derived endotoxin translocation and NF-kappaB activation on the aggravating mechanism of severe acute pancreatitis (SAP) and of treatment with pyrrolidine dithiocarbamate (PDTC) on rats with SAP. METHODS: SD rats were randomly divided into sham operation group (SO), SAP group, SAP + lipopolysaccharide(LPS) group, pyrrolidine dithiocarbamate (PDTC) treatment group and LPS group. Biochemical parameters and cytokines were examined in the serum. Multiple organs pathological slices were examined. Expression of NF-kappaB mRNA in the liver tissue was detected by RT-PCR. Activation of NF-kappaB by the method of streptomycin avidin-peroxidase (SP) and expression of NF-kappaB p65 protein and its binding activity were analyzed by Western blot and electrophoretic mobidity shift assay (EMSA). RESULTS: Compared with sham operation group, the concentration of TNF-alpha, alanine aminotransferase (ALT), and diamine oxidase (DAO) in serum significantly increased in SAP + LPS group (P < 0.05). Pathological changes were markedly observed in tissues and the expression of NF-kappaB mRNA in the liver significantly increased (P < 0.05) also, the activation of NF-kappaB and binding activity of NF-kappaB p65 protein in the liver markedly increased (P < 0.01) in SAP + LPS group. Treatment with PDTC markedly reduced concentration of ALT, DAO and TNF-alpha, and the expression of NF-kappaB, and the pathologic scores, as well as significantly decreased the expression of NF-kappaB p65 protein. CONCLUSION: The activation and overexpression of NF-kappaB may participate in the aggravating mechanism of SAP. Treatment with PDTC has a protective effect on multiple organs damage in SAP. SN - 1751-2980 UR - https://www.unboundmedicine.com/medline/citation/19236545/Effects_of_gut_barrier_dysfunction_and_NF_kappaB_activation_on_aggravating_mechanism_of_severe_acute_pancreatitis_ L2 - https://doi.org/10.1111/j.1751-2980.2008.00360.x DB - PRIME DP - Unbound Medicine ER -