• 四川大學華西醫(yī)院肝膽胰外科（成都 610041）;

目的 介紹胰腺星狀細胞在胰腺纖維化中的作用及抗胰腺纖維化研究進展。
方法 復習相關文獻資料并作綜述。
結果 胰腺星狀細胞的活化與胰腺纖維化密切相關，抑制胰腺星狀細胞活化可為臨床治療慢性胰腺炎提供新的途徑。
結論 胰腺星狀細胞是胰腺纖維化發(fā)病的關鍵環(huán)節(jié)，并逐漸成為抗胰腺纖維化及治療慢性胰腺炎的重要靶標。

引用本文： 鄭振江,向光明,劉續(xù)寶. 胰腺星狀細胞在胰腺纖維化中的作用. 中國普外基礎與臨床雜志, 2010, 17(8): 876-879. doi: 復制

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1. Masamune A, Shimosegawa T. Signal transduction in pancreatic stellate cells [J]. J Gastroenterol, 2009; 44(4): 249260.
2. Apte MV, Haber PS, Applegate TL, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture [J]. Gut, 1998; 43(1): 128133.
3. Saotome T, Inoue H, Fujimiya M, et al. Morphological and immunocytochemical identification of periacinar fibroblastlike cells derived from human pancreatic acini [J]. Pancreas, 1997; 14(4): 373382.
4. Haber PS, Keogh GW, Apte MV, et al. Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis [J]. Am J Pathol, 1999; 155(4): 10871095.
5. Shimizu K. Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis [J]. J Gastroenterol, 2008; 43(11): 823832.
6. Jaster R, Emmrich J. Crucial role of fibrogenesis in pancreatic diseases [J]. Best Pract Res Clin Gastroenterol, 2008; 22(1): 1729.
7. Mews P, Phillips P, Fahmy R, et al. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis [J]. Gut, 2002; 50(4): 535541.
8. Aoki H, Ohnishi H, Hama K, et al. Existence of autocrine loop between interleukin6 and transforming growth factorβ1 in activated rat pancreatic stellate cells [J]. J Cell Biochem, 2006; 99(1): 221228.
9. Schneider E, SchmidKotsas A, Zhao J, et al. Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells [J]. Am J Physiol Cell Physiol, 2001; 281(2): C532C543.
10. Yadav D, Whitcomb DC. The role of alcohol and smoking in pancreatitis [J]. Nat Rev Gastroenterol Hepatol, 2010; 7 (3): 131145.
11. Ohnishi N, Miyata T, Ohnishi H, et al. Activin A is an autocrine activator of rat pancreatic stellate cells: potential role of follistatin for pancreatic fibrosis [J]. Gut, 2003; 52(10): 14871493.
12. Philipps PA, Wu MJ, Kumar RK, et al. Cell migration: a novel aspect of pancreatic stellate cell biology [J]. Gut, 2003; 52(5): 677682.
13. Leung PS. The physiology of a local reninangiotensin system in the pancreas [J]. J Physiol, 2007; 580(Pt1): 3137.
14. Reinehr R, Zoller S, KlonowskiStumpe H, et al. Effects of Angiotensin II on rat pancreatic stellate cells [J]. Pancreas, 2004; 28(2): 129137.
15. Owens DM, Keyse SM. Differential regulation of MAP kinase signalling by dualspecificity protein phosphatases [J]. Oncogene, 2007; 26(22): 32033213.
16. Jaster R, Sparmann G, Emmrich J, et al. Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells [J]. Gut, 2002; 51(4): 579584.
17. 楊小艷, 鄭勇. Smad7對TGFβ/SMAD的調節(jié)及其在肝纖維化中的作用 [J]. 臨床肝膽胰雜志, 2007; 23(6): 467469.
18. 馬松林, 趙秋, 龔勇, 等. 纖維化胰腺組織中TGFβ1、Smad3、Smad7的表達及意義 [J]. 世界華人消化雜志, 2007; 15(2): 185188.
19. Dooley S, Hamzavi J, Breitkopf K, et al. Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [J]. Gastroenterology, 2003; 125(1): 178191.
20. McCarroll JA, Phillips PA, Kumar RK, et al. Pancreatic stellate cell migration: role of the phosphatidylinositol 3kinase (PI3kinase) pathway [J]. Biochem Pharmacol, 2004; 67(6): 12151225.
21. Masamune A, Kikuta K, Satoh M, et al. Rho kinase inhibitors block activation of pancreatic stellate cells [J]. Br J Pharmacol, 2003; 140(7): 12921302.
22. 劉續(xù)寶. 慢性胰腺炎的診斷和治療 [J]. 中國普外基礎與臨床雜志, 2007; 14(4): 385387.
23. Rockey DC, Maher JJ, Jarnagin WR, et al. Inhibition of rat hepatic lipocyte activation in culture by IFNγ [J]. Hepatology, 1992; 16(3): 776784.
24. Baumert JT, Sparmann G, Emmrich J, et al. Inhibitory effect of interferons on pancreatic stellate cell activation [J]. World J Gastroenterol, 2006; 12(6): 896901.
25. Rane SG, Reddy EP. Janus kinases: components of multiple signaling pathways [J]. Oncogene, 2000; 19(49): 56625679.
26. 黃茜, 陳少夫, 鄭宏. 干擾素α2b對胰腺纖維化大鼠Ⅲ型膠原和纖維連接蛋白表達的影響 [J]. 胰腺病學, 2007; 7(5): 326328.
27. 鮑華英, 陳榮華. 姜黃素的研究進展 [J]. 國際兒科學雜志, 2003; 30(5): 254256.
28. Masamune A, Suzuki N, Kikuta K, et al. Curcumin blocks activation of pancreatic stellate cells [J]. J Cell Biochem, 2006; 97(5): 10801093.
29. 侯懿耕, 張園園, 賈潔, 等. 過氧化物酶體增殖物激活受體γ在肝星狀細胞靜止表型維持中的作用 [J]. 世界華人消化雜志, 2008; 16(33): 37653768.
30. Van Westerloo DJ, Florquin S, deBoer AM, et al. Therapeutic effects of troglitazone in experimental chronic pancreatitis in mice [J]. Am J Pathol, 2005; 166(3): 721728.
31. Shimuzu K, Shiratori K, Kobayashi M, et al. Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPAR γindependent mechanism [J]. Pancreas, 2004; 29(1): 6774.
32. Tahmasebi M, Puddefoot JR, Inwang ER, et al. The tissue reninangiotensin system in human pancreas [J]. J Endocrinol, 1999; 161(2): 317322.
33. Kuno A, Yamada T, Masuda K, et al. Angiotensinconverting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats [J]. Gastroenterology, 2003; 124(4): 10101019.
34. 張汝玲, 劉文濱, 王興鵬, 等.Ⅰ型血管緊張素Ⅱ受體拮抗劑對胰腺星狀細胞的影響 [J]. 中華消化雜志, 2006; 26(9): 598601.
35. Nathan JD, Romac J, Peng RY, et al. Protection against chronic pancreatitis and pancreatic fibrosis in mice over expressing pancreatic secretory trypsin inhibitor [J]. Pancreas, 2010; 39(1): e24e30.
36. Su SB, Motoo Y, Iovanna JL, et al. Effect of camostat mesilate on the expression of PancreaticAssociated Protein (PAP), p8 and cytokines in rat spontaneous chronic pancreatitis [J]. Pancreas, 2001; 23(2): 134140.
37. McCarroll JA, Phillips PA, Santucci N, et al. Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis [J]. Gut, 2006; 55(1): 7989.
38. Masamune A, Satoh M, Kikuta K, et al. Endothelin1 stimulates contraction and migration of rat pancreatic stellate cells [J]. World J Gastroenterol, 2005; 11(39): 61446151.
39. 羅璐, 于鋒, 戴德哉. 內皮素受體拮抗劑波生坦與其他藥物的相互作用 [J]. 藥學進展, 2007; 31(10): 452457.
40. Fitzner B, Brock P, Holzhüter SA, et al. Synergistic growth inhibitory effects of the dual endothelin1 receptor antagonist bosentan on pancreatic stellate and cancer cells [J]. Dig Dis Sci, 2009; 54(2): 309320.
  1. 1. Masamune A, Shimosegawa T. Signal transduction in pancreatic stellate cells [J]. J Gastroenterol, 2009; 44(4): 249260.
  2. 2. Apte MV, Haber PS, Applegate TL, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture [J]. Gut, 1998; 43(1): 128133.
  3. 3. Saotome T, Inoue H, Fujimiya M, et al. Morphological and immunocytochemical identification of periacinar fibroblastlike cells derived from human pancreatic acini [J]. Pancreas, 1997; 14(4): 373382.
  4. 4. Haber PS, Keogh GW, Apte MV, et al. Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis [J]. Am J Pathol, 1999; 155(4): 10871095.
  5. 5. Shimizu K. Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis [J]. J Gastroenterol, 2008; 43(11): 823832.
  6. 6. Jaster R, Emmrich J. Crucial role of fibrogenesis in pancreatic diseases [J]. Best Pract Res Clin Gastroenterol, 2008; 22(1): 1729.
  7. 7. Mews P, Phillips P, Fahmy R, et al. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis [J]. Gut, 2002; 50(4): 535541.
  8. 8. Aoki H, Ohnishi H, Hama K, et al. Existence of autocrine loop between interleukin6 and transforming growth factorβ1 in activated rat pancreatic stellate cells [J]. J Cell Biochem, 2006; 99(1): 221228.
  9. 9. Schneider E, SchmidKotsas A, Zhao J, et al. Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells [J]. Am J Physiol Cell Physiol, 2001; 281(2): C532C543.
  10. 10. Yadav D, Whitcomb DC. The role of alcohol and smoking in pancreatitis [J]. Nat Rev Gastroenterol Hepatol, 2010; 7 (3): 131145.
  11. 11. Ohnishi N, Miyata T, Ohnishi H, et al. Activin A is an autocrine activator of rat pancreatic stellate cells: potential role of follistatin for pancreatic fibrosis [J]. Gut, 2003; 52(10): 14871493.
  12. 12. Philipps PA, Wu MJ, Kumar RK, et al. Cell migration: a novel aspect of pancreatic stellate cell biology [J]. Gut, 2003; 52(5): 677682.
  13. 13. Leung PS. The physiology of a local reninangiotensin system in the pancreas [J]. J Physiol, 2007; 580(Pt1): 3137.
  14. 14. Reinehr R, Zoller S, KlonowskiStumpe H, et al. Effects of Angiotensin II on rat pancreatic stellate cells [J]. Pancreas, 2004; 28(2): 129137.
  15. 15. Owens DM, Keyse SM. Differential regulation of MAP kinase signalling by dualspecificity protein phosphatases [J]. Oncogene, 2007; 26(22): 32033213.
  16. 16. Jaster R, Sparmann G, Emmrich J, et al. Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells [J]. Gut, 2002; 51(4): 579584.
  17. 17. 楊小艷, 鄭勇. Smad7對TGFβ/SMAD的調節(jié)及其在肝纖維化中的作用 [J]. 臨床肝膽胰雜志, 2007; 23(6): 467469.
  18. 18. 馬松林, 趙秋, 龔勇, 等. 纖維化胰腺組織中TGFβ1、Smad3、Smad7的表達及意義 [J]. 世界華人消化雜志, 2007; 15(2): 185188.
  19. 19. Dooley S, Hamzavi J, Breitkopf K, et al. Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [J]. Gastroenterology, 2003; 125(1): 178191.
  20. 20. McCarroll JA, Phillips PA, Kumar RK, et al. Pancreatic stellate cell migration: role of the phosphatidylinositol 3kinase (PI3kinase) pathway [J]. Biochem Pharmacol, 2004; 67(6): 12151225.
  21. 21. Masamune A, Kikuta K, Satoh M, et al. Rho kinase inhibitors block activation of pancreatic stellate cells [J]. Br J Pharmacol, 2003; 140(7): 12921302.
  22. 22. 劉續(xù)寶. 慢性胰腺炎的診斷和治療 [J]. 中國普外基礎與臨床雜志, 2007; 14(4): 385387.
  23. 23. Rockey DC, Maher JJ, Jarnagin WR, et al. Inhibition of rat hepatic lipocyte activation in culture by IFNγ [J]. Hepatology, 1992; 16(3): 776784.
  24. 24. Baumert JT, Sparmann G, Emmrich J, et al. Inhibitory effect of interferons on pancreatic stellate cell activation [J]. World J Gastroenterol, 2006; 12(6): 896901.
  25. 25. Rane SG, Reddy EP. Janus kinases: components of multiple signaling pathways [J]. Oncogene, 2000; 19(49): 56625679.
  26. 26. 黃茜, 陳少夫, 鄭宏. 干擾素α2b對胰腺纖維化大鼠Ⅲ型膠原和纖維連接蛋白表達的影響 [J]. 胰腺病學, 2007; 7(5): 326328.
  27. 27. 鮑華英, 陳榮華. 姜黃素的研究進展 [J]. 國際兒科學雜志, 2003; 30(5): 254256.
  28. 28. Masamune A, Suzuki N, Kikuta K, et al. Curcumin blocks activation of pancreatic stellate cells [J]. J Cell Biochem, 2006; 97(5): 10801093.
  29. 29. 侯懿耕, 張園園, 賈潔, 等. 過氧化物酶體增殖物激活受體γ在肝星狀細胞靜止表型維持中的作用 [J]. 世界華人消化雜志, 2008; 16(33): 37653768.
  30. 30. Van Westerloo DJ, Florquin S, deBoer AM, et al. Therapeutic effects of troglitazone in experimental chronic pancreatitis in mice [J]. Am J Pathol, 2005; 166(3): 721728.
  31. 31. Shimuzu K, Shiratori K, Kobayashi M, et al. Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPAR γindependent mechanism [J]. Pancreas, 2004; 29(1): 6774.
  32. 32. Tahmasebi M, Puddefoot JR, Inwang ER, et al. The tissue reninangiotensin system in human pancreas [J]. J Endocrinol, 1999; 161(2): 317322.
  33. 33. Kuno A, Yamada T, Masuda K, et al. Angiotensinconverting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats [J]. Gastroenterology, 2003; 124(4): 10101019.
  34. 34. 張汝玲, 劉文濱, 王興鵬, 等.Ⅰ型血管緊張素Ⅱ受體拮抗劑對胰腺星狀細胞的影響 [J]. 中華消化雜志, 2006; 26(9): 598601.
  35. 35. Nathan JD, Romac J, Peng RY, et al. Protection against chronic pancreatitis and pancreatic fibrosis in mice over expressing pancreatic secretory trypsin inhibitor [J]. Pancreas, 2010; 39(1): e24e30.
  36. 36. Su SB, Motoo Y, Iovanna JL, et al. Effect of camostat mesilate on the expression of PancreaticAssociated Protein (PAP), p8 and cytokines in rat spontaneous chronic pancreatitis [J]. Pancreas, 2001; 23(2): 134140.
  37. 37. McCarroll JA, Phillips PA, Santucci N, et al. Vitamin A inhibits pancreatic stellate cell activation: implications for treatment of pancreatic fibrosis [J]. Gut, 2006; 55(1): 7989.
  38. 38. Masamune A, Satoh M, Kikuta K, et al. Endothelin1 stimulates contraction and migration of rat pancreatic stellate cells [J]. World J Gastroenterol, 2005; 11(39): 61446151.
  39. 39. 羅璐, 于鋒, 戴德哉. 內皮素受體拮抗劑波生坦與其他藥物的相互作用 [J]. 藥學進展, 2007; 31(10): 452457.
  40. 40. Fitzner B, Brock P, Holzhüter SA, et al. Synergistic growth inhibitory effects of the dual endothelin1 receptor antagonist bosentan on pancreatic stellate and cancer cells [J]. Dig Dis Sci, 2009; 54(2): 309320.