Segersvärd Ralf, Tsai Jon A, Herrington Margery K, Wang Feng
Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Obesity (Silver Spring). 2008 Jan;16(1):23-8. doi: 10.1038/oby.2007.27.
Obesity is a negative prognostic factor in patients with critical illnesses such as acute pancreatitis (AP). The outcome of AP is determined by the severity of systemic inflammation and organ dysfunction. In a previous study, we found that AP caused more deaths in obese rats than in lean rats. In the present study, we examined whether the effect of obesity on rats with AP is associated with distinct alterations in inflammatory cytokine expression in organs involved in AP.
AP was induced in lean and obese Zucker rats by pancreatic infusion of taurocholic acid. All survivors were killed 8 h later. Gene transcripts for two proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)) and two anti-inflammatory cytokines (IL-10 and pancreatitis-associated protein (PAP)) were determined in the pancreas, liver, and lungs by quantitative real-time polymerase chain reaction. The severity of AP was assessed by means of histology and serology.
Obese AP rats had higher TNF-alpha mRNA in all organs examined, lower IL-10 and IL-6 mRNA in the pancreas, and lower PAP mRNA in the liver, compared to lean AP rats. Lean and obese AP rats had similar pancreatic lesions as assessed by histology. However, steatohepatitis and increased serum alanine amino transferase levels, which are indications of hepatic injury, were present in obese but not lean AP rats.
Our findings suggest that altered inflammatory cytokine expression and increased vulnerability in the liver underlie the detrimental influence of obesity on AP.
肥胖是急性胰腺炎（AP）等危重病患者的不良预后因素。AP的结局由全身炎症和器官功能障碍的严重程度决定。在先前的一项研究中，我们发现AP在肥胖大鼠中导致的死亡比瘦大鼠更多。在本研究中，我们研究了肥胖对AP大鼠的影响是否与AP相关器官中炎症细胞因子表达的明显改变有关。
通过向胰腺输注牛磺胆酸在瘦和肥胖的 Zucker 大鼠中诱导AP。8小时后处死所有存活的大鼠。通过定量实时聚合酶链反应测定胰腺、肝脏和肺中两种促炎细胞因子（白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α））以及两种抗炎细胞因子（IL-10和胰腺炎相关蛋白（PAP））的基因转录本。通过组织学和血清学评估AP的严重程度。
与瘦AP大鼠相比，肥胖AP大鼠在所有检查的器官中TNF-α mRNA水平更高，胰腺中IL-10和IL-6 mRNA水平更低，肝脏中PAP mRNA水平更低。通过组织学评估，瘦和肥胖AP大鼠的胰腺病变相似。然而，肥胖AP大鼠存在脂肪性肝炎和血清丙氨酸氨基转移酶水平升高，这是肝损伤的指标，而瘦AP大鼠则没有。
我们的研究结果表明，炎症细胞因子表达的改变和肝脏易损性增加是肥胖对AP产生有害影响的基础。
