论文部分内容阅读
目的探讨肥大细胞(MC)在大鼠胰腺组织纤维化形成中的作用和机制。方法建立经逆行胆胰管注射2％三硝基苯磺酸(TNBS)诱导大鼠慢性胰腺炎模型,将大鼠分为三组,每组40只,分别用肥大细胞膜稳定剂色甘酸钠和MC激动剂48/80化合物及生理盐水进行干预,并于第3、7、14、21 和28天处死动物。H-E染色观察胰腺组织病理学改变;Van Gieson染色观察胰腺组织纤维化情况;硫堇蓝染色观察大鼠慢性胰腺炎过程中MC分布、形态和数量的改变;免疫组化染色观察大鼠慢性胰腺炎α-平滑肌肌动蛋白(α-SMA)、转化生长因子(TGF)β1的表达;逆转录-多聚酶链反应(RT-PCR)观察血管紧张素Ⅱ1型(AT1)和2型(AT2)受体蛋白的表达。结果 2％TNBS胰管内注射后可于第4周引起典型大鼠胰腺组织纤维化,在胰腺纤维化区域可见大量Ⅰ型胶原沉积。在此过程中MC存在着活化及脱颗粒。胰腺组织α-SMA、TGFβ1、AT1和AT2 mRNA蛋白制模早期表达即为阳性,至第4周时最强。与对照(生理盐水)组比较,色甘酸钠组MC数量及脱颗粒现象明显减少,α-SMA、TGFβ1蛋白表达和 AT1、AT2受体mRNA表达明最减少:48／80化合物组MC数量及脱颗粒现象明显增多,上述各指标的表达均有不同程度的增加。结论 MC参与TNBS诱导的大鼠慢性胰腺炎的炎症和纤维化的发生及发展,其机制可能与MC促进胰腺星状细胞活化,上调血管紧张素Ⅱ受体表达等介导了胰腺纤维化的形成。
Objective To investigate the role and mechanism of mast cells (MC) in the formation of pancreatic fibrosis in rats. Methods Chronic pancreatitis induced by 2% trinitrobenzene sulfonic acid (TNBS) was induced by retrograde cholangiopancreatic duct in rats. The rats were divided into three groups of 40 rats, each group was treated with mast cell membrane stabilizer cromolyn sodium and MC agonist 48/80 compound and saline, and animals were sacrificed on days 3, 7, 14, 21 and 28. The histopathological changes of pancreas were observed by HE staining; the fibrosis of pancreas was observed by Van Gieson staining; the distribution, shape and number of MC in chronic pancreatitis of rats were observed by using thionine blue staining; The expression of α-smooth muscle actin (α-SMA) and transforming growth factor β1 (TGF-β1) was detected by RT-PCR. The expressions of angiotensin Ⅱ type 1 (AT1) and type 2 Protein expression. Results The pancreatic duct fibrosis induced by 2% TNBS in the fourth week after pancreatic ductal injury in rats showed extensive deposition of type I collagen in the area of pancreatic fibrosis. In the process of MC there is activation and degranulation. Pancreatic tissue α-SMA, TGFβ1, AT1 and AT2 mRNA expression early expression is positive, the strongest by 4 weeks. Compared with the control (saline) group, the number and degranulation of MC in cromolyn sodium group were significantly decreased, and the expressions of α-SMA, TGFβ1 and AT1, AT2 receptor mRNA were the lowest in 48/80 group The phenomenon of particles increased obviously, the expression of each above-mentioned index increased to some extent. Conclusion MC participates in the pathogenesis and progression of inflammation and fibrosis induced by TNBS in rats with chronic pancreatitis. Its mechanism may be related to the activation of pancreatic stellate cells and the activation of pancreatic stellate cells and the up-regulation of angiotensin Ⅱ receptor expression. .