Modified Xiaochaihu Decoction (加味小柴胡汤) Promotes Collagen Degradation and Inhibits Pancreatic Fibrosis in Chronic Pancreatitis Rats

Abstract

Objective

To investigate the effect of Modified Xiaochaihu Decoction (MXD, 加味小柴胡汤) on collagen degradation in rats with chronic pancreatitis (CP).

Methods

Rats were injected dibutyltin dichloride (DBTC, 7 mg/kg of body weight) into the right caudal vein to induce CP model. Thirty heallhy male Wistar rats were randomly divided into three groups by a random number table: the control, the model and the treatment groups. Rats of treatment group were administered MXD (10 g/kg of body weight) orally once daily starting from the day post-model establishment. Pancreatic tissues were harvested after 28-day feeding and fibrosis was evaluated by picro-sirius red staining. The contents of collagen type I and III were detected using enzymelinked immunosorbent assay (ELISA), the expression of matrix metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase 1 (TIMP1) was analyzed by Western blot and real-time polymerase chain reaction (PCR).

Results

The fibrosis scoring of pancreatic tissues, the concentrations of collagen type I and III, the expression levels of MMP13 and TIMP1 proteins and mRNA in the model group were all increased compared with the control group (P<0.05). After treatment with MXD, the fibrosis scoring of pancreatic tissues, the concentrations of collagen type I and III, the expression levels of MMP13 proteins and mRNA in the teatment group were all decreased compared with the model group (P<0.05), but there were no significant differences in the expression levels of TIMP1 proteins and mRNA (P>0.05).

Conclusions

MXD could promote collagen degradation and reverse pancreatic fibrosis in CP rats via a mechanism involve up-regulation of MMP13 expression.

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References

  1. 1.

    Gress TM, Müller-Pillasch F, Lerch MM, Friess H, Büchler M, Beger HG, et al. Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in CP. Z Gastroenterol 1994;32:221–225.

    CAS  PubMed  Google Scholar 

  2. 2.

    Zhang SK, Tsui NC, Li DH, Yao GW, Wang YN. Expression of transforming growth factor beta1/Sma-and Mad-related proteins in rat with chronic pancreatitis induced by dibutyltin dichloride. Pancreas 2010;39:252–253.

    Article  Google Scholar 

  3. 3.

    Schwer CI, Mutschler M, Stoll P, Goebel U, Humar M, Hoetzel A, et al. Carbon monoxide releasing molecule-2 inhibits pancreatic stellate cell proliferation by activating p38 mitogen-activated protein kinase/heme oxygenase-1 signaling. Mol Pharmacol 2010;77:660–669.

    CAS  Article  Google Scholar 

  4. 4.

    Fortunato F, Berger I, Gross ML, Rieger P, Buechler MW, Werner J. Immune-compromised state in the rat pancreas after chronic alcohol exposure: the role of peroxisome proliferatoractivated receptor gamma. J Pathol 2007;213:441–452.

    CAS  Article  Google Scholar 

  5. 5.

    Shek FW, Benyon RC, Walker FM, McCrudden PR, Pender SL, Williams EJ, et al. Differential and synergistic effects of platelet-derived growth factor-BB and transforming growth factor-beta1 on activated pancreatic stellate cells. Pancreas 2005;31:156–167.

    Article  Google Scholar 

  6. 6.

    Musso O, Clément B, Théret N. Assessing matrix metalloproteinase expression and activity in hepatocellular carcinomas. Methods Mol Med 2000;45:139–156.

    CAS  PubMed  Google Scholar 

  7. 7.

    Choi EK, Kim MH, Jang SJ, Lee KH, Hwang CY, Moon SH, et al. Differences in pancreatic immunohistochemical staining profiles of TGF-beta1, MMP-2, and TIMP-2 between autoimmune and alcoholic chronic pancreatitis. Pancreas 2009;38:739–745.

    CAS  Article  Google Scholar 

  8. 8.

    Kordes C, Brookmann S, Häussinger D, Klonowski-Stumpe H. Differential and synergistic effects of platelet-derived growth factor-BB and transforming growth factor-beta1 on activated pancreatic stellate cells. Pancreas 2005;31:156–167.

    CAS  Article  Google Scholar 

  9. 9.

    Phillips PA, McCarroll JA, Park S, Wu MJ, Pirola R, Korsten M, et al. Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Gut 2003;52:275–282.

    CAS  Article  Google Scholar 

  10. 10.

    Zhang SK, Cui NQ, Zhuo YZ, Li DH, Liu JH. Modified Xiaochaihu Decoction prevents the progreßsion of CP in rats possibly by inhibiting transforming growth factor-β1/Smaand Mad-related proteins signaling pathway. Chin J Integr Med 2013;19:935–939.

    Article  Google Scholar 

  11. 11.

    Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol 2007;292:G1009–G1018.

    CAS  Article  Google Scholar 

  12. 12.

    Wang W, Liao Z, Li G, Li ZS, Chen J, Zhan XB, et al. Incidence of pancreatic cancer in Chinese patients with CP. Pancreatology 2011;11: 16–23.

    Article  Google Scholar 

  13. 13.

    Huang H, Luo Y. Cognition of Chinese medicine about chronic pancreatitis and its treating progression. Modern J Integr Tradit Chin West Med (Chin) 2007;16:3762–3763.

    Google Scholar 

  14. 14.

    Cui ZG, Cui NQ, Zhang DP. Clinical study of the individualized step therapy on CP. Chin J Surg Integr Tradit West Med (Chin) 2011;17:451–454.

    Google Scholar 

  15. 15.

    Lin WR, Yen TH, Lim SN, Perng MD, Lin CY, Su MY, et al. Granulocyte colony-stimulating factor reduces fibrosis in a mouse model of chronic pancreatitis. PLoS One 2014;9:e116229.

    Article  Google Scholar 

  16. 16.

    Endo H, Niioka M, Sugioka Y, Itoh J, Kameyama K, Okazaki I, et al. Matrix metalloproteinase-13 promotes recovery from experimental liver cirrhosis in rats. Pathobiology 2011;78:239–252.

    CAS  Article  Google Scholar 

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Authors

Contributions

Zhang SK and Cui NQ designed this study; Zhuo YZ, Hu JG, Liu JH, Li DH and Cui LH performed the experiments; Zhang SK wrote the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Shu-kun Zhang.

Additional information

Conflict of Interest

The authors declare that they have no competing interests.

Supported by the National Natural Science Foundation of China (No. 81102686)

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Zhang, Sk., Cui, Nq., Zhuo, Yz. et al. Modified Xiaochaihu Decoction (加味小柴胡汤) Promotes Collagen Degradation and Inhibits Pancreatic Fibrosis in Chronic Pancreatitis Rats. Chin. J. Integr. Med. 26, 599–603 (2020). https://doi.org/10.1007/s11655-017-2413-0

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Keywords

  • Modified Xiaochaihu Decoction
  • collagen degradation
  • chronic pancreatitis rats
  • matrix metalloproteinase 13
  • tissue inhibitor of metalloproteinase 1