Zyromski Nicholas J, Mathur Abhishek, Pitt Henry A, Wade Terence E, Wang Sue, Swartz-Basile Deborah A, Prather Andrew D, Lillemoe Keith D
Department of Surgery, Indiana University School of Medicine, 535 Barnhill Dr. RT 130, Indianapolis, IN 46202, USA.
J Gastrointest Surg. 2009 May;13(5):831-8. doi: 10.1007/s11605-009-0824-8. Epub 2009 Feb 19.
Obesity is a risk factor for increased severity of acute pancreatitis. Adipocytes produce adiponectin, an anti-inflammatory molecule that is paradoxically decreased in the setting of obesity. We have shown that adiponectin concentration inversely mirrors the severity of pancreatitis in obese mice. Cannabinoid receptor CB-1 blockade increases circulating adiponectin concentration. We, therefore, hypothesize that blockade of CB-1 would increase adiponectin and attenuate pancreatitis severity.
Forty lean (C57BL/6J) and 40 obese (Lep(Db)) mice were studied. Half of the mice in each strain received intraperitoneal injection of the CB-1 antagonist rimonabant (10 mg/kg daily for 7 days); the others received vehicle. Pancreatitis was induced by intraperitoneal injection of cerulein (50 microg/g hourly x 6). Pancreatitis severity was determined by histology. Pancreatic chemokine and proinflammatory cytokine concentrations were measured by ELISA.
Rimonabant treatment significantly increased circulating adiponectin concentration in obese mice (p < 0.03 vs. vehicle). After induction of pancreatitis, obese mice treated with rimonabant had significantly decreased histologic pancreatitis (p < 0.001), significantly lower pancreatic tissue levels of monocyte chemoattractant protein-1 (p = 0.03), tumor necrosis factor-alpha (p < 0.001), interleukin-6 (p < 0.001), and myeloperoxidase (p = 0.006) relative to vehicle-treated animals.
In obese mice, cannabinoid receptor CB-1 blockade with rimonabant attenuates the severity of acute pancreatitis by an adiponectin-mediated mechanism.
肥胖是急性胰腺炎严重程度增加的一个风险因素。脂肪细胞产生脂联素，这是一种抗炎分子，而在肥胖情况下其水平反而会降低。我们已经表明，脂联素浓度与肥胖小鼠胰腺炎的严重程度呈负相关。大麻素受体CB-1阻断可增加循环脂联素浓度。因此，我们假设阻断CB-1会增加脂联素并减轻胰腺炎的严重程度。
研究了40只瘦型（C57BL/6J）小鼠和40只肥胖型（Lep(Db)）小鼠。每个品系的一半小鼠接受腹腔注射CB-1拮抗剂利莫那班（每日10 mg/kg，共7天）；其余小鼠接受溶剂对照。通过腹腔注射雨蛙素（每小时50 μg/g，共6次）诱导胰腺炎。通过组织学确定胰腺炎的严重程度。通过酶联免疫吸附测定法测量胰腺趋化因子和促炎细胞因子浓度。
利莫那班治疗显著增加了肥胖小鼠循环脂联素浓度（与溶剂对照相比，p < 0.03）。诱导胰腺炎后，与接受溶剂对照的动物相比，接受利莫那班治疗的肥胖小鼠组织学胰腺炎显著减轻（p < 0.001），胰腺组织中单核细胞趋化蛋白-1（p = 0.03）、肿瘤坏死因子-α（p < 0.001）、白细胞介素-6（p < 0.001）和髓过氧化物酶（p = 0.006）水平显著降低。
在肥胖小鼠中，利莫那班阻断大麻素受体CB-1通过脂联素介导的机制减轻急性胰腺炎的严重程度。
