胰腺星状细胞移植对胰岛功能和形态的影响-东南大学学报医学版

胰腺星状细胞移植对胰岛功能和形态的影响

单位：东南大学附属中大医院内分泌科, 东南大学医学院糖尿病研究所, 江苏南京 210009

分类号：R-33;R335.6

出版年·卷·期（页码）：2015·34·第一期（12-16）

摘要：

目的:通过胰腺星状细胞(PSC)移植的体内研究来观察PSC对胰岛β细胞及血糖代谢的影响。方法:PSC体外分离培养,并通过胰腺移植入正常血糖的Wistar和高血糖Goto-Kakizaki (GK)大鼠体内。移植16周后糖耐量试验和糖化血红蛋白(glycated haemoglobin, HbA1c) 检测胰岛功能;胰岛素免疫荧光染色观察胰岛β细胞;马松染色评估胰岛纤维化。结果:PSC移植进一步损伤了GK大鼠胰岛功能,导致了血糖和HbA1c的升高,减少了胰岛素分泌,加重了胰岛的破坏和纤维化,但未观察到PSC移植对Wistar大鼠的影响。结论:PSC在糖尿病环境下可以加重胰岛破坏,可能参与2型糖尿病β细胞衰竭的进程。

Objective: To assess the effects of pancreatic stellate cell PSC on β-cell function and glucose homeostasis. Methods:PSCs were isolated and cultured in vitro, then were transplanted into the pancreas of normoglycemic Wistar and hyperglycemic Goto-Kakizaki (GK) rats. Sixteen weeks post-transplantation, β-cell function was assessed by glucose tolerance tests and measurements of HbA1c. Immunofluorescent staining for insulin and Masson's trichromestain were performed to assess the β-cell mass and fibrosis, respectively. Results: PSCs transplantation exacerbated the impaired β-cell function in GK rats, increased blood glucose and HbA1c levels, decreased insulin secretion, reduced β-cell mass and increased islet fibrosis. In contrast, PSCs transplantation had no significant effects in Wistar rats. Conclusion: PSCs induce β-cell failure, suggesting that they may play a potential role in the progression of type 2 diabetes mellitus.

参考文献：

[1] PRENTKI M,NOLAN C J.Islet beta cell failure in type 2 diabetes[J].J Clin Invest,2006,116(7):1802-1812.
[2] HOMO-DELARCHE F,CALDERARI S,IRMINGER J C,et al.Islet inflammation and fibrosis in a spontaneous model of type 2 diabetes,the GK rat[J].Diabetes,2006,55(6):1625-1633.
[3] LEE E,RYU G R,KO S H,et al.Antioxidant treatment may protect pancreatic beta cells through the attenuation of islet fibrosis in an animal model of type 2 diabetes[J].Biochem Biophys Res Commun,2011,414(2):397-402.
[4] MASAMUNE A,WATANABE T,KIKUTA K,et al.NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells[J].Am J Physiol Gastrointest Liver Physiol,2008,294(1):G99-G108.
[5] KO S H,KWON H S,KIM S R,et al.Ramipril treatment suppresses islet fibrosis in Otsuka Long-Evans Tokushima fatty rats[J].Biochem Biophys Res Commun,2004,316(1):114-122.
[6] KIM J W,KO S H,CHO J H,et al.Loss of beta-cells with fibrotic islet destruction in type 2 diabetes mellitus[J].Front Biosci,2008,13(1):6022-6033.
[7] SAITO R,YAMADA S,YAMAMOTO Y,et al.Conophylline suppresses pancreatic stellate cells and improves islet fibrosis in Goto-Kakizaki rats[J].Endocrinology,2012,153(2):621-630.
[8] APTE M V,WILSON J S.Alcohol-induced pancreatic injury[J].Best Pract Res Clin Gastroenterol,2003,17(4):593-612.
[9] BACHEM M G,ZHOU Z,ZHOU S,et al.Role of stellate cells in pancreatic fibrogenesis associated with acute and chronic pancreatitis[J].J Gastroenterol Hepatol,2006,21(3):S92-S96.
[10] SIECH M,ZHOU Z,ZHOU S,et al.Stimulation of stellate cells by injured acinar cells:a model of acute pancreatitis induced by alcohol and fat (VLDL) [J].Am J Physiol Gastrointest Liver Physiol,2009,297(6):G1163-1171.
[11] HAYDEN M R,SOWERS J R.Isletopathy in type 2 diabetes mellitus:implications of islet RAS,islet fibrosis,islet amyloid,remodeling,and oxidative stress[J].Antioxid Redox Signal,2007,9(7):891-910.
[12] HAYDEN M R.Islet amyloid and fibrosis in the cardiometabolic syndrome and type 2 diabetes mellitus[J].J Cardiometab Syndr,2007,2(1):70-75.
[13] KAIHARA M,NAKAMURA Y,SUGOMOTO T,et al.Olmesartan and temocapril prevented the development of hyperglycemia and the deterioration of pancreatic islet morphology in Otsuka-Long-Evans-Tokushima Fatty rats[J].Acta Med Okayama,2009,63(1):35-42.
[14] FUSE M,YOKOI N,SHONIHARA M,et al.Identification of a major locus for islet inflammation and fibrosis in the spontaneously diabetic Torii rat[J].Physiol Genomics,2008,35(1):96-105.
[15] APTE M,PIROLA R,WILSON J.New insights into alcoholic pancreatitis and pancreatic cancer[J].J Gastroenterol Hepatol,2009,24(Suppl):S51-56.
[16] KIKUTA K,MASAMUNE A,HAMADA S,et al.Pancreatic stellate cells reduce insulin expression and induce apoptosis in pancreatic beta-cells[J].Biochem Biophys Res Commun,2013,433(3):292-297.
[17] BACHEM M G,SCHNEIDER E,GROSS H,et al.Identification,culture,and characterization of pancreatic stellate cells in rats and humans[J].Gastroenterology,1998,115(2):421-432.
[18] SCHORMANN W,HAMMERSEN F J,BRULPORT M,et al.Tracking of human cells in mice[J].Histochem Cell Biol,2008,130(2):329-338.
[19] DONG Q Y,CHEN L,GAO G Q,et al.Allogeneic diabetic mesenchymal stem cells transplantation in streptozotocin-induced diabetic rat[J].Clin Invest Med,2008,31(6):E328-337.
[20] APTE M V,PIROLA R C,WILSON J S.Pancreatic stellate cells:a starring role in normal and diseased pancreas[J].Front Physiol,2012,3:344-358.
[21] BACHEM M G,SCHUNEMANN M,RAMADANI M,et al.Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells[J].Gastroenterology,2005,128(4):907-921.
[22] EHSES J A,LACRAZ G,GIROIX M H,et al.IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat[J].Proc Natl Acad Sci USA,2009,106(33):13998-14003.
[23] PORTHA B,LACRAZ G,CHAVEY A,et al.Islet structure and function in the GK rat[J].Adv Exp Med Biol,2010,654:479-500.
[24] MOSEN H,OSTENSON C G,LUNDQUIST I,et al.Impaired glucose-stimulated insulin secretion in the GK rat is associated with abnormalities in islet nitric oxide production[J].Regul Pept,2008,151(1-3):139-146.
[25] LACRAZ G,GIROIX M H,KASSIS N,et al.Islet endothelial activation and oxidative stress gene expression is reduced by IL-1Ra treatment in the type 2 diabetic GK rat[J].PLoS One,2009,4(9):e6963.
[26] KOYAMA M,WADA R,SAKURABA H,et al.Accelerated loss of islet beta cells in sucrose-fed Goto-Kakizaki rats,a genetic model of non-insulin-dependent diabetes mellitus[J].Am J Pathol,1998,153(2):537-545.
[27] 刘洁,王尧.血糖波动与糖尿病并发症的关系[J].现代医学,2010,38(2):200-203.

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