Puig-Diví V, Molero X, Vaquero E, Salas A, Guarner F, Malagelada J
Digestive System Research Unit, Hospital General Universitari Vall d'Hebron, Barcelona, Spain.
Digestion. 1999 Mar-Apr;60(2):166-74. doi: 10.1159/000007643.
Instillation of trinitrobenzene sulfonic acid (TNBS) into the rat pancreatic ducts induces morphological changes resembling human chronic pancreatitis. In humans, alcoholism is commonly associated with chronic pancreatitis, but ethanol feeding fails to induce pancreatitis in experimental animals. We hypothesized that ethanol would manifest its pathogenetic effects on a duct-injured pancreas.
Chronic pancreatitis was induced in rats by instillation of TNBS into pancreatic ducts. Thereafter, rats were fed a normal chow diet with or without ethanol supplementation. Control rats received vehicle and a normal diet. A separate group of vehicle-treated rats were also fed with ethanol. At 2 and 4 weeks pancreata were excised and processed for morphological examination or for biochemical assays. From crude homogenates, protein and hydroxyproline were quantified. After sonication, homogenates were also assayed for amylase and DNA. An oral glucose tolerance test was performed on the fourth week.
TNBS induced chronic fibrogenic pancreatitis that was associated with a reduction in pancreatic weight, DNA, protein and amylase as compared to control rats. Ethanol feeding to TNBS-treated animals slowed weight gain, increased fasting glucose and impaired glucose tolerance test. Larger areas of gland atrophy were observed with a striking disruption of the normal architecture of the islets. Ethanol accelerated pancreatic involution and collagen deposition as measured by total amylase, protein, DNA and hydroxyproline content.
In TNBS chronic pancreatitis, active fibrogenesis is associated with progressive atrophy of glandular elements. Morphological and biochemical parameters are aggravated by sustained ethanol intake.
向大鼠胰管内注入三硝基苯磺酸（TNBS）可诱发类似人类慢性胰腺炎的形态学改变。在人类中，酒精中毒常与慢性胰腺炎相关，但给实验动物喂食乙醇并不能诱发胰腺炎。我们推测乙醇会对受损伤的胰腺发挥其致病作用。
通过向大鼠胰管内注入TNBS诱导慢性胰腺炎。此后，给大鼠喂食正常饲料，部分添加乙醇，部分不添加。对照大鼠给予赋形剂和正常饮食。另一组接受赋形剂处理的大鼠也喂食乙醇。在第2周和第4周时，切除胰腺并进行形态学检查或生化检测。从粗匀浆中定量检测蛋白质和羟脯氨酸。超声处理后，匀浆还用于检测淀粉酶和DNA。在第4周进行口服葡萄糖耐量试验。
与对照大鼠相比，TNBS诱发了慢性纤维增生性胰腺炎，伴有胰腺重量、DNA、蛋白质和淀粉酶减少。给接受TNBS处理的动物喂食乙醇减缓了体重增加，提高了空腹血糖并损害了葡萄糖耐量试验。观察到更大面积的腺体萎缩，胰岛正常结构受到显著破坏。通过总淀粉酶、蛋白质、DNA和羟脯氨酸含量测定，乙醇加速了胰腺退化和胶原沉积。
在TNBS诱导的慢性胰腺炎中，活跃的纤维生成与腺泡成分的进行性萎缩相关。持续摄入乙醇会加重形态学和生化参数的改变。
