Inoue Masanobu, Ino Yoshifumi, Gibo Junya, Ito Tetsuhide, Hisano Terumasa, Arita Yoshiyuki, Nawata Hajime
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Pancreas. 2002 Nov;25(4):e64-70. doi: 10.1097/00006676-200211000-00023.
Recently, dibutyltin dichloride (DBTC) was reported to induce pancreatic fibrosis within 28 days in rats, but it is not clear that the induced condition should be considered chronic pancreatitis.
The aim of this study was to clarify whether the pancreatic fibrosis induced by DBTC can be regarded as chronic pancreatitis. Furthermore, we examined the relation of monocyte chemoattractant protein-1 (MCP-1) to the development of pancreatic fibrosis in this model. DBTC solution was injected into the right jugular vein in rats, and biochemical and histologic changes were measured at days 1, 3, 7, 14, and 28.
Microscopically, inflammatory cell infiltration was evident in the pancreas at days 1 and 3, mononuclear cell infiltration was observed at days 7, 14, and 28, and pancreatic fibrosis was pronounced 7 days later. At day 28, interstitial fibrosis and atrophy of the gland and ductlike tubular complex had progressed. DBTC produced a significant decrease in the contents of pancreatic protein and amylase, whereas the pancreatic hydroxyproline content increased. Serum and pancreatic MCP-1 concentration significantly increased compared with the control group. Furthermore, the expression of PDGF mRNA in the pancreas increased following the MCP-1 elevation.
These results suggest that this experimental model of pancreatic fibrosis induced by DBTC in rats was useful as a chronic pancreatitis model and that MCP-1 may play an important role in the development of pancreatic fibrosis.
最近,有报道称二氯化二丁基锡(DBTC)可在28天内诱导大鼠胰腺纤维化,但尚不清楚这种诱导情况是否应被视为慢性胰腺炎。
本研究的目的是阐明DBTC诱导的胰腺纤维化是否可被视为慢性胰腺炎。此外,我们在该模型中研究了单核细胞趋化蛋白-1(MCP-1)与胰腺纤维化发展的关系。将DBTC溶液注入大鼠右颈静脉,并在第1、3、7、14和28天测量生化和组织学变化。
显微镜下,第1天和第3天胰腺有明显的炎症细胞浸润,第7、14和28天观察到单核细胞浸润,7天后胰腺纤维化明显。在第28天,间质纤维化以及腺体和导管样管状复合体的萎缩有所进展。DBTC使胰腺蛋白质和淀粉酶含量显著降低,而胰腺羟脯氨酸含量增加。与对照组相比,血清和胰腺MCP-1浓度显著升高。此外,随着MCP-1升高,胰腺中血小板衍生生长因子(PDGF)mRNA的表达增加。
这些结果表明,DBTC诱导的大鼠胰腺纤维化实验模型可作为慢性胰腺炎模型,且MCP-1可能在胰腺纤维化发展中起重要作用。