外源性瘦素通过抑制NF-κB活性降低大鼠重症急性胰腺炎促炎因子的表达

Exogenous ieptin reduce blood inflammatory cytokines in severe rats acute pancreatitis by suppressing NF-κB activity

目的探讨外源性瘦素（1eptin）对重症急性胰腺炎（SAP）大鼠胰腺组织NF-κB活性及血清炎症因子的影响。方法Wister大鼠36只，分为假手术组、SAP动物模型组、瘦素治疗组，各12只。采用5％牛磺胆酸钠胰胆管顺行注射胰胆管制模，治疗组行外源性瘦素腹腔注射，6h后采血、取胰腺标本，检测各组动物血淀粉酶、瘦素、肿瘤坏死因子α、白细胞介素1β的含量，采用免疫组织化学法测定NF-κB活性，并对大鼠胰腺组织进行病理学评分。结果制模6h后血淀粉酶、leptin、TNF-α、IL-κB水平均升高，胰腺组织NF-κB活性增高，胰腺组织出血坏死明显，外源性瘦素干预组可显著降低血淀粉酶、TNF-α及IL-1β水平，NF-κB活性降低，胰腺组织出血坏死程度减轻，NF-κB活性与炎症因子水平呈正相关。结论外源性瘦素可能通过通过抑制NF-κB活性，降低促炎性因子TNF-α、IL—1β的产生，从而达到对SAP大鼠的保护作用。

Objective To investigate the effect of leptin on transcription factor nuclear-κB （NF-KB） activity of pancreatic tissue and blood inflammatory cytokines （TNF-α, IL-1β） in severe acute pancreatitis. Methods Thirty-six rats were randomly divided into three groups, including sham group （group A, n = 12）, AP model group（group B, n = 12） and Leptin treatment group （group C, n = 12）. SAP was induced by intraductal injection of 5% sodium tanrocholate into the pancreatic duct. Exogenous leptin was injected i.p. fifteen minutes later. The concentration of serum amylase, leptin, TNF-α, IL-1βwere measured by radioimmunoassay 6 hours later. NF-κB activity of the pancreatic tissue were measured by immunohistochemistry. The changes of pathology of the pancreas were observed. Results The levels of serum amylase, cytokine TNF-α and IL-1β were significantly reduced in group C, and the levels of serum leptin were significantly increased in group C. NF-κB activity in the pancreatic tissue in group B were significantly higher than that in group A. However, NF-κB activity of the pancreatic tissue in group C were significantly lower than that in group B. Furthermore, the extent of necrosis of the pancreatic tissue was relieved. Conclusion Exogenous leptin protected the rats pancreas against damage by sodium taurocholate. The protective effects of exogenous leptin were attributive to the reduction in cytokines TNF-α, IL-1β. The possible protective mechanism was＇that leptin decreased NF-κB activity.