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Study of dexamethasone, baicalin and octreotide on brain injury of rats with severe acute pancreatitis

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Abstract

Objective

To investigate the protecting effects of dexamethasone (DXM), baicalin and octreotide on brain injury of rats with severe acute pancreatitis (SAP) and explore their underlying mechanism.

Methods

This experiment was divided into two different parts: (1) In the first part, 90 SAP rats were randomly divided into a model control group and a DXM treated group (n = 45, respectively). (2) In the second part, 135 SAP rats were randomly divided into a model control group, a baicalin treated group and an octreotide treated group (n = 45, respectively). In two different experiments, the same number of normal rats were considered as the sham-operated group (n = 45, respectively). At 3, 6 and 12 h after operation, the pathological changes in the brain were observed. The expression levels of nuclear factor-κB (NF-κB), Bax and Bcl-2 proteins were detected and apoptosis indexes were calculated, using brain tissue microarray section.

Results

(1) First part: The expression levels of Bax and Bcl-2 were significantly higher in the DXM treated group than those in the model control group at different time points, while the content of NF-κB protein and pathological changes were significantly lower in the treated group than those in the model control group (P < 0.05, P < 0.01 or P < 0.001). But the apoptotic indexes of brain tissue were not significantly different at different time points (P > 0.05). (2) Second part: At all time points after operation, the expression levels of NF-κB in the brain of treated groups were, to varying degrees, significantly lower than those in the model control group while the expression levels of Bcl-2 protein in baicalin and octreotide group were significantly higher than those in model control group (P < 0.01, P < 0.01 and P < 0.05, respectively). At 12 h after operation, the expression level of Bax protein in baicalin treated group was significantly higher than those in model control group and octreotide treated group (P < 0.05 and P < 0.01, respectively).

Conclusions

Dexamethasone, baicalin and octreotide can exert protective effects against brain injury in SAP rats mainly through inhibiting the expression of NF-κB protein.

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References

  1. Zhang XP, Ye Q, Jiang XG, Ma ML, Zhu FB, Zhang RP, Cheng QH. Preparation method of an ideal model of multiple organ injury of rat with severe acute pancreatitis. World J Gastroenterol. 2007;13(34):4566–73.

    PubMed  CAS  Google Scholar 

  2. Lu XS, Qiu F, Li YX, Li JQ, Fan QQ, Zhou RG. Effect of lower-molecular weight heparin in the prevention of pancreatic encephalopathy in the patient with severe acute pancreatitis. Pancreas. 2010;39(4):516–9.

    Article  PubMed  Google Scholar 

  3. Zhang XP, Tian H. Pathogenesis of pancreatic encephalopathy in severe acute pancreatitis. Hepatobiliary Pancreat Dis Int. 2007;6(2):134–40.

    PubMed  CAS  Google Scholar 

  4. Sun GH, Yang YS, Liu QS, Cheng LF, Huang XS. Pancreatic encephalopathy and Wernicke encephalopathy in association with acute pancreatitis: a clinical study. World J Gastroenterol. 2006;12(26):4224–7.

    PubMed  Google Scholar 

  5. Suzuki M, Shimizu T, Kudo T, Shoji H, Ohtsuka Y, Yamashiro Y. Octreotide prevents l-asparaginase-induced pancreatic injury in rats. Exp Hematol. 2008;36(2):172–80.

    Article  PubMed  CAS  Google Scholar 

  6. Barreto SG, Carati CJ, Schloithe AC, Toouli J, Saccone GT. Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice. HPB (Oxford). 2010;12(6):403–11.

    Article  Google Scholar 

  7. Xiping Z, Guanghua F, Jinxian H, Weihong W, Rujun X, Wei Z, Jing Y, Qijun Y, Meijuan Y, Qing W, Lini F. Baicalin protects thymus of rats with severe acute pancreatitis. Inflammation. 2010;33(3):157–65.

    Article  PubMed  Google Scholar 

  8. Liu X, Liu Q, Pan C. Early preventive treatment for severe acute pancreatitis combined with lung injury. Chin J Traumatol. 2002;5(3):190–2. In chinese.

    PubMed  Google Scholar 

  9. Ramudo L, Yubero S, Manso MA, Sanchez-Recio J, Weruaga E, De Dios I. Effects of dexamethasone on intercellular adhesion molecule 1 expression and inflammatory response in necrotizing acute pancreatitis in rats. Pancreas. 2010;39(7):1057–63.

    Article  PubMed  CAS  Google Scholar 

  10. Kandil E, Lin YY, Bluth MH, Zhang H, Levi G, Zenilman ME. Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins. World J Gastroenterol. 2006;12(42):6806–11.

    PubMed  CAS  Google Scholar 

  11. Xiping Z, Ruiping Z, Binyan Y, Li Z, Hanqing C, Wei Z, Rongchao Y, Jing Y, Wenqin Y, Jinjin B. Protecting effects of a large dose of dexamethasone on spleen injury of rats with severe acute pancreatitis. J Gastroenterol Hepatol. 2010;25(2):302–8.

    Article  PubMed  Google Scholar 

  12. Zhu H, Wang Z, Xing Y, Gao Y, Ma T, Lou L, Lou J, Gao Y, Wang S, Wang Y. Baicalin reduces the permeability of the blood–brain barrier during hypoxia in vitro by increasing the expression of tight junction proteins in brain microvascular endothelial cells. J Ethnopharmacol. 2011 Sep 3. (Epub ahead of print).

  13. Lixuan Z, Jingcheng D, Wenqin Y, Jianhua H, Baojun L, Xiaotao F. Baicalin attenuates inflammation by inhibiting NF-kappaB activation in cigarette smoke induced inflammatory models. Pulm Pharmacol Ther. 2010;23(5):411–9.

    Article  PubMed  Google Scholar 

  14. Zhang X, Tian H, Wu C, Ye Q, Jiang X, Chen L, Cai Y, Xu R, Yuan W. Effect of baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis. Pancreas. 2009;38(7):732–8.

    Article  PubMed  CAS  Google Scholar 

  15. Xue D, Zhang W, Zhang Y, Wang H, Zheng B, Shi X. Adjusting effects of baicalin for nuclear factor-kappaB and tumor necrosis factor-alpha on rats with caerulein-induced acute pancreatitis. Mediators Inflamm. 2006;2006(5):262–95.

    Google Scholar 

  16. Luo XM, Han YM, Tang ZH, et al. Experimental studies on the protective effect of Baicalin on mouse brain. Chinese Journal of Traditional Medical Science and Technology. 2005;21(1):1–5 (In Chinese).

    Google Scholar 

  17. Wang CY, Jiang YL, Zhi HY, et al. Protective effect of baicalin on brain injury. Chinese Traditional and Herbal Drugs. 2004;35:188–9 (In Chinese).

    Google Scholar 

  18. Jia Y, Yang Y, Zhou Y, Song Y, Liu L, Song J, Wang X, Zhong L, Yu X. Differentiation of rat bone marrow stromal cells into neuron induced by baicalin. Zhonghua Yi Xue Za Zhi. 2002;82(19):1337–41. In Chinese.

    PubMed  CAS  Google Scholar 

  19. Heo HJ, Kim DO, Choi SJ, Shin DH, Lee CY. Potent Inhibitory effect of flavonoids in Scutellaria baicalensis on amyloid beta protein-induced neurotoxicity. J Agric Food Chem. 2004;52(13):4128–32.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang XP, Zhang L, Yang P, Zhang RP, Cheng QH. Protective effects of baicalin and octreotide on multiple organ injury in severe acute pancreatitis. Dig Dis Sci. 2008;53(2):581–91.

    Article  PubMed  CAS  Google Scholar 

  21. Zhang XP, Zhang L, He JX, Zhang RP, Cheng QH, Zhou YF, Lu B. Experimental study of therapeutic efficacy of Baicalin in rats with severe acute pancreatitis. World J Gastroenterol. 2007;13(5):717–24.

    PubMed  CAS  Google Scholar 

  22. Zhang XP, Tian H, Lai YH, Chen L, Zhang L, Cheng QH, Yan W, Li Y, Li QY, He Q, Wang F. Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis. World J Gastroenterol. 2007;13(38):5079–89.

    PubMed  CAS  Google Scholar 

  23. Xiping Z, Hua T, Hanqing C, Li C, Zhiwei W, Keyi W, Wei Y, Yun L, Qingyu L, Qing H, Fei W. The protecting effects and mechanisms of Baicalin and Octreotide on heart injury in rats with SAP. Mediators Inflamm. 2007;2007:19469.

    PubMed  Google Scholar 

  24. Gomez G, Lee HM, He Q, Englander EW, Uchida T, Greeley GH Jr. Acute pancreatitis signals activation of apoptosis-associated and survival genes in mice. Exp Biol Med (Maywood). 2001;226(7):692–700.

    CAS  Google Scholar 

  25. Bonior J, Jaworek J, Kot M, Konturek SJ, Pawlik WW. Endotoxemia in the infant rats modulates HSP60 protein level in the pancreatic acinar cells. J Physiol Pharmacol. 2007;58(Suppl 3):189–98.

    PubMed  Google Scholar 

  26. Zhang XP, Chen L, Hu QF, Tian H, Xu RJ, Wang ZW, Wang KY, Cheng QH, Yan W, Li Y, Li QY, He Q, Wang F. Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis. World J Gastroenterol. 2007;13(41):5506–11.

    PubMed  CAS  Google Scholar 

  27. Zhang XP, Zhang L, Wang Y, Cheng QH, Wang JM, Cai W, Shen HP, Cai J. Study of the protective effects of dexamethasone on multiple organ injury in rats with severe acute pancreatitis. JOP. 2007;8(4):400–12.

    PubMed  Google Scholar 

  28. Zhang XP, Zhang L, Xu HM, Xu YP, Cheng QH, Wang JM, Shen HP. Application of tissue microarrays to study the influence of dexamethasone on NF-kappaB expression of pancreas in rat with severe acute pancreatitis. Dig Dis Sci. 2008;53(2):571–80.

    Article  PubMed  CAS  Google Scholar 

  29. Zhang X, Chen L, Luo L, Tian H, Feng G, Cai Y, Xu R, Wang K, Wang Z. Study of the protective effects of dexamethasone on ileum mucosa injury in rats with severe acute pancreatitis. Pancreas. 2008;37(3):e74–82.

    Article  PubMed  CAS  Google Scholar 

  30. Xiping Z, Li C, Miao L, Hua T. Protecting effects of dexamethasone on thymus of rats with severe acute pancreatitis. Mediators Inflamm. 2007;2007:723–61.

    Google Scholar 

  31. Pavle G, Ana S, Sanja S, Dejan R, Nenad I, Aleksandar K, Nada P, Borivoje K, Stijak L, Branislav S, Zoran M, Djordje B. SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors. Hepatogastroenterology. 2010;57(98):349–53.

    PubMed  Google Scholar 

  32. Gong D, Zhang P, Ji D, Chen Z, Li W, Li J, Li L, Liu Z. Improvement of immune dysfunction in patients with severe acute pancreatitis by high-volume hemofiltration: a preliminary report. Int J Artif Organs. 2010;33(1):22–9.

    PubMed  Google Scholar 

  33. Zhang XP, Tian H, Wu DJ, Feng GH, Chen L, Zhang J, Xu RJ, Cai Y, Ju TF, Xie Q. Pathological changes in multiple organs of rats with severe acute pancreatitis treated by baicalin and Octreotide. Hepatobiliary Pancreat Dis Int. 2009;8(1):85–92.

    PubMed  CAS  Google Scholar 

  34. Zhang X, Feng G, Weng W, Liang J, Lin N, Cai Y, Xu R, Zhou N, Yuan M, Yuan W, Xia X. Protective effects of baicalin and Octreotide on intestinal mucosa of rats with severe acute pancreatitis. Turk J Gastroenterol. 2009;20(2):108–15.

    PubMed  CAS  Google Scholar 

  35. Farkas G, Márton J, Nagy Z, Mándi Y, Takács T, Deli MA, Abrahám CS. Experimental acute pancreatitis results in increased blood–brain barrier permeability in the rat: a potential role for tumor necrosis factor and interleukin 6. Neurosci Lett. 1998;242(3):147–50.

    Article  PubMed  CAS  Google Scholar 

  36. Guo J, Huang ZW, Fan JY, Chen Y, He FQ. Risk factor analysis of severe acute pancreatitis complicated by pancreatic encephalopathy. Zhong Xi Yi Jie He Xue Bao. 2008;6(4):352–4.

    Article  PubMed  Google Scholar 

  37. Xiping Z, Jun F, Jie Z, Bingyan Y, Jing M, Wei Z, Jing Y, Penghui J, Wenqin Y, Ninnin Z, Jiao H. Influence of Dexamethasone on the expression levels of P-selectin protein in multiple organs of rats with severe acute pancreatitis. Inflamm Res. 2010;59(1):31–9.

    Article  PubMed  Google Scholar 

  38. Sato T, Hanada M, Bodrug S, Irie S, Iwama N, Boise LH, Thompson CB, Golemis E, Fong L, Wang HG. Interactions among members of the Bcl-2 protein family analyzed with a yeast two-hybrid system. Proc Natl Acad Sci. 1994;91(20):9238–42.

    Article  PubMed  CAS  Google Scholar 

  39. Gu JC, Wang Y, Zhang ZT, Xue JG, Li JS, Zhou YZ. Effects of human interleukin 10 gene transfer on the expression of Bcl-2 Bax and apoptosis of hepatocyte in rats with acute hemorrhagic necrotizing pancreatitis. Chin Med J (Engl). 2005;118(19):1658–60.

    CAS  Google Scholar 

  40. Sugiyama Y, Kato S, Abe M, Mitsufuji S, Takeuchi K. Different effects of Dexamethasone and the nitric oxide synthase inhibitor L-NAME on caerulein-induced rat acute pancreatitis, depending on the severity. Inflammopharmacol. 2005;13(1–3):291–301.

    Article  CAS  Google Scholar 

  41. Wang ZF, Pan CE, Lu Y, Liu SG, Zhang GJ, Zhang XB. The role of inflammatory mediators in severe acute pancreatitis and regulation of glucocorticoids. Hepatobiliary Pancreat Dis Int. 2003;2(3):458–62.

    PubMed  CAS  Google Scholar 

  42. Paszt A, Takács T, Rakonczay Z, et al. The role of the glucocorticoid-dependent mechanism in the progression of sodium taurocholate- induced acute pancreatitis in the rat. Pancreas. 2004;29(1):75–82.

    Article  PubMed  CAS  Google Scholar 

  43. Huang JH, Huang XH, Chen ZY, Zhen QS, Sun RY. Dose conversion among different animals and healthy volunteers in pharmacological study. Chin J Clinic Pharma Therapeut. 2004;9(9):1069–72. In Chinese.

    Google Scholar 

  44. Srinivas NR. Baicalin, an emerging multi-therapeutic agent: pharmacodynamics, pharmacokinetics, and considerations from drug development perspectives. Xenobiotica. 2010;40(5):357–67.

    Article  PubMed  CAS  Google Scholar 

  45. Xue X, Qu XJ, Yang Y, Sheng XH, Cheng F, Jiang EN, Wang JH, Bu W, Liu ZP. Baicalin attenuates focal cerebral ischemic reperfusion injury through inhibition of nuclear factor κB p65 activation. Biochem Biophys Res Commun. 2010;403(3–4):398–404.

    Article  PubMed  CAS  Google Scholar 

  46. Tu XK, Yang WZ, Liang RS, Shi SS, Chen JP, Chen CM, Wang CH, Xie HS, Chen Y, Ouyang LQ. Effect of baicalin on matrix metalloproteinase-9 expression and blood-brain barrier permeability following focal cerebral ischemia in rats. Neurochem Res. 2011 Jun 17.

  47. Li J, Wang R, Tang C. Somatostatin and octreotide on the treatment of acute pancreatitis - basic and clinical studies for three decades. Curr Pharm Des. 2011;17(16):1594–601.

    Article  PubMed  CAS  Google Scholar 

  48. Li ZS, Pan X, Zhang WJ, Gong B, Zhi FC, Guo XG, Li PM, Fan ZN, Sun WS, Shen YZ, Ma SR, Xie WF, Chen MH, Li YQ. Effect of octreotide administration in the prophylaxis of post-ERCP pancreatitis and hyperamylasemia: a multicenter, placebo-controlled, randomized clinical trial. Am J Gastroenterol. 2007;102(1):46–51.

    Article  PubMed  CAS  Google Scholar 

  49. Thomopoulos KC, Pagoni NA, Vagenas KA, Margaritis VG, Theocharis GI, Nikolopoulou VN. Twenty-four hour prophylaxis with increased dosage of octreotide reduces the incidence of post-ERCP pancreatitis. Gastrointest Endosc. 2006;64(5):726–31.

    Article  PubMed  Google Scholar 

  50. Rakonczay Z Jr, Hegyi P, Takács T, McCarroll J, Saluja AK. The role of NF-kappaB activation in the pathogenesis of acute pancreatitis. Gut. 2008;57(2):259–67.

    Article  PubMed  CAS  Google Scholar 

  51. Algül H, Tando Y, Schneider G, Weidenbach H, Adler G, Schmid RM. Acute experimental pancreatitis and NF-kappaB/Rel activation. Pancreatology. 2002;2(6):503–9.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province (No. 2003C130 and No. 2004C142), Foundation Project for Medical Science and Technology of Zhejiang province (No. 2003B134), Grave Foundation Project for Technological and Development of Hangzhou (No. 2003123B19), Intensive Foundation Project for Technology of Hangzhou (No. 2004Z006), Foundation Project for Medical Science and Technology of Hangzhou (No. 2003A004) and Foundation Project for Technology of Hangzhou (No. 2005224). We state that this paper is original, that we have no financial interest in the company or its competitors, and that all authors meet the criteria for authorship. We abided by the ethics rules in this animal experiment study. Ethics committee approval of our hospital was secured, no rats were abused, and mercy killing was conducted when the observation time for this study was over.

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Authors and Affiliations

  1. Department of General Surgery, Hangzhou First People’s Hospital, Hangzhou, 310006, Zhejiang, China

    Zhang Xiping

  2. Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China

    Ou Jingmin

  3. Class 0302 in three Department of Clinical Medicine, Medical College of Zhejiang University, Hangzhou, 310058, Zhejiang Province, China

    Wang Chun

  4. The first College of Clinical Medicine, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310006, Zhejiang Province, China

    Yan Ping

  5. Department of Gynecology and Obstetrics, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, 310006, Zhejiang Province, China

    Ye Qian

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  1. Ou Jingmin
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Correspondence to Zhang Xiping.

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Responsible Editor: Artur Bauhofer.

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Jingmin, O., Xiping, Z., Chun, W. et al. Study of dexamethasone, baicalin and octreotide on brain injury of rats with severe acute pancreatitis. Inflamm. Res. 61, 265–275 (2012). https://doi.org/10.1007/s00011-011-0408-4

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