TNF-α介导重症急性胰腺炎肾上腺细胞的凋亡

The Role of Tumor Necrosis Factor-α in Pancreatitis Associated Adrenal Cells' Apoptosis of Severe Acute Pancreatitis

目的观察肿瘤坏死因子-α(TNF-α)在重症急性胰腺炎(SAP)肾上腺细胞凋亡中的作用。方法采用随机数字表法将40只雄性Wistar大鼠随机分为假手术组(SO组)和SAP组,SAP组又再分为3、6、12及24 h4个亚组,每组8只大鼠。采用5%牛黄胆酸钠(0.1 m L/100 g)逆行胆胰管注射法建立SAP大鼠模型,测定各组大鼠血清淀粉酶及脂肪酶水平,观察胰腺和肾上腺组织的病理学改变,并进行评分;用TUNEL法检测肾上腺细胞凋亡情况,并比较各组大鼠的凋亡指数;采用Western blot法检测肾上腺组织中TNF-α及Caspase-3蛋白的表达。结果造模术后各时间点SAP组大鼠血清淀粉酶和脂肪酶水平以及胰腺组织和肾上腺组织的病理学评分均较SO组显著升高(P<0.05);随病程延长,SAP组大鼠肾上腺细胞凋亡指数也进行性升高,并均高于SO组(P<0.05);SAP组大鼠肾上腺组织中TNF-α和Caspase-3蛋白的相对表达量也逐渐增高,24 h时略有下降,但均高于SO组(P<0.05)。结论 TNF-α可能参与了SAP时的肾上腺损伤,可能通过激活Caspase-3在SAP肾上腺细胞凋亡中发挥重要作用。

Objective To investigate The role of tumor necrosis factor-a （TNF-α） in pancreatitis-associated adrenal ceils＇ apoptosis of severe acute pancreatitis （SAP）. Methods Forty Wistar rats were randomly divided into sham operation group （SO group） and SAP group by random number method, the SAP group was divided into 3, 6, 12, and 24 h 4 subgroups, 8 rats in each group. SAP model was induced by retrograde injection of 5% sodium taurocholate into the bilipancreatic duct. At 3, 6, 12, and 24 h after operation, serum amylase and lipase was measured, adrenal injury was evaluated by histological examination, apoptosis of the adrenal cells was observed by TUNEL method, and expressions of TNF-α and Caspase-3 protein were detected by Western blot. Results The levels of serum AMY and LIP, histopathological scores of pancreatic tissues and adrenal tissues at each time point after operation in SAP group increased significantly than SO group （P〈0.05）. With the duration extension of SAP, the apoptosis index of adrenal cells in SAP group progressively heightened, and were higher than those in the SO group （P〈0.05）. And the expressions of TNF-α and Caspase-3 protein in adrenal tissues of SAP group gradually increased, at 24 h this data slightly decreased, but still higher than SO group （P〈0.05）. Conclusion TNF-α may be involved in the pathogenesis of adrenal injury in SAP rats by activate the protein expression of Caspase-3.