Zhang Deyu, Li Wanshun, Wang Meiqi, Yin Hua, Xia Chuanchao, Li Keliang, Huang Haojie
Department of Gastroenterology, First Affiliated Hospital, Naval Medical University, Shanghai, China.
Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Front Oncol. 2022 Jul 6;12:947133. doi: 10.3389/fonc.2022.947133. eCollection 2022.
The current study aimed to develop a new chronic pancreatitis and spontaneous pancreatic cancer model on C57/BL6 mouse through retrograde pancreatic duct injection of dibutyltin dichloride (DBTC) and explore its basic pathological changes as compared to the previous published chronic pancreatitis model through tail vein injection of DBTC with alcohol drinking. C57/BL6 mice were randomly divided into 3 groups: CG (control group; n = 15), VG (tail vein injection of DBTC (8 mg/kg) with 10% alcohol drinking group; n = 20), and PG (retrograde pancreatic duct injection of DBTC group (1 mg/kg); n = 30). Five mice in each group were sacrificed at a specific time point after the first treatment. The pathological section was observed. The activities of amylase, bilirubin, and hyaluronic acid in serum were determined. The expression of fibronectin, COL1A1, α-SMA, MMP-1, and TIMP-1 in the pancreas was assayed. Severe fibrosis of the pancreas with inflammatory cell infiltration could be observed on day 21 in the PG. In the VG, slight fibrosis of the pancreas with inflammatory cell infiltration was observed on day 28. There were significant differences in serum amylase, bilirubin, and hyaluronic acid levels between the PG and VG. The protein level of COL1A1 and α-SMA significantly increased in the PG. The mRNA expression of TIMP-1 is upregulated and the MMP-1 mRNA level is downregulated in the PG. Finally, typical neoplastic pathological change is significantly obvious in the PG. In conclusion, we established and validated a new chronic pancreatitis (CP) and spontaneous pancreatic cancer mouse model through retrograde injection of DBTC into the pancreatic duct. Previously reported mouse model through tail vein injection of DBTC with alcohol drinking could not cause obvious CP and neoplastic pathological change in mice.
本研究旨在通过逆行胰管注射二丁基二氯化锡（DBTC）在C57/BL6小鼠上建立一种新的慢性胰腺炎和自发性胰腺癌模型，并与先前发表的通过尾静脉注射DBTC并饮用酒精的慢性胰腺炎模型相比，探索其基本病理变化。将C57/BL6小鼠随机分为3组：CG（对照组；n = 15）、VG（尾静脉注射DBTC（8 mg/kg）并饮用10%酒精组；n = 20）和PG（逆行胰管注射DBTC组（1 mg/kg）；n = 30）。在首次治疗后的特定时间点处死每组中的5只小鼠。观察病理切片。测定血清中淀粉酶、胆红素和透明质酸的活性。检测胰腺中纤连蛋白、COL1A1、α-SMA、MMP-1和TIMP-1的表达。在PG组中，第21天时可观察到胰腺严重纤维化并伴有炎性细胞浸润。在VG组中，第28天时观察到胰腺轻度纤维化并伴有炎性细胞浸润。PG组和VG组之间血清淀粉酶、胆红素和透明质酸水平存在显著差异。PG组中COL1A1和α-SMA的蛋白水平显著升高。PG组中TIMP-1的mRNA表达上调，MMP-1的mRNA水平下调。最后，PG组中典型的肿瘤病理变化明显。总之，我们通过将DBTC逆行注射到胰管中建立并验证了一种新的慢性胰腺炎（CP）和自发性胰腺癌小鼠模型。先前报道的通过尾静脉注射DBTC并饮用酒精的小鼠模型不会在小鼠中引起明显 的CP和肿瘤病理变化。
