NF-κB对急性坏死性胰腺炎大鼠甲状旁腺激素受体表达和低钙血症的影响

目的 探讨NF-κB对ANP大鼠甲状旁腺激素受体(PTH1R)表达及低钙血症的影响.方法 将雄性SD大鼠24只按完全随机法分为对照组、ANP组和四氢化吡咯二硫代氨基甲酸脂预处理组(PDTC组),各8只.以5%牛磺脱氧胆酸钠逆行胰胆管注射建立ANP模型.观察6 h后各组血清钙浓度以及胰腺组织病理改变,蛋白免疫印渍法检测肾脏和骨组织NF-κB、PTH1R蛋白表达,RT-PCR检测肾脏和骨组织FTH1R mRNA表达.结果 对照组、ANP组和PDTC组血钙浓度分别为(2.31±0.03)mmol/L、(2.01±0.03)mmol/L和(2.12±0.05)mmol/L,3组间差异显著(P<0.05).ANP组肾脏和骨组织的NF-κB蛋白表达量分别为1.53±0.08和0.47±0.19;PDTC组分别为0.61±0.13和0.36±0.06,两组差异显著(P<0.05).ANP组肾脏和骨组织PTH1R mRNA的表达量分别为0.27±0.08和0.29±0.06,PTH1R蛋白表达分别为0.87±0.07和0.31±0.09;PDTC组分别为0.57±0.27和0.37±0.11,1.13±0.17和0.68±0.15,两组差异显著(P<0.05).ANP组NF-κB活性较对照组明显升高,PTH1R表达明显下降;与ANP组比较,PDTC组NF-κB活性降低,血清钙水平明显升高,PTH1R的表达上调(P<0.05).结论 NF-κB可能通过间接下调组织PTH1R的表达,致血清钙显著下降.PDTC对改善ANP低钙血症有一定意义.

Effect of nuclear factor-kappa B on parathyroid hormone receptor expression and hypocalcaemia in rats with acute necrotizing pancreatitis

Objective To investigate the effect of nuclear factor-kappa B(NF-κB) on the expression of parathyroid hormone receptor (PTH1R) and serum calcium level in rats with acute necrotizing pancreatitis (ANP) rats. Methods 24 male Sprague-Dawley rats were randomly divided into sham operation group (SO), ANP group, pyrrolidine dithiocarbamat (PDTC, an inhibitor of NF-κB) pretreated ANP group (PDTC), with 8 rats each group. ANP model was induced by injecting 5% sodium taurodeoxyebolate into biliary pancreatic duct. Serum calcium was measured and the expression of NF-κB was determined by western blot and the expression of PTH1R was examined by RT-PCR plus western blot 6 h after ANP induction. Results The NF-κB proteins of bone and kidney tissues in ANP group were 1.53±0.08 and 0.47±0.19, respectively; in PDTC group they were 0.61±0.13 and 0.36±0.06 with significant difference (P<0.05). The PTH1R mRNA expressions of bone and kidney in ANP group were 0.27±0.08 and 0.29±0.06, respectively; the PTH1R proteins expressions were 0.87±0.07 and 0.31±0.09, respectively. The corresponding values in PDTC group were 0.57±0.27 and 0.37±0.11, 1.13±0.17 and 0.68±0.15, respectively, with significant difference (P<0.05). The activity of NF-κB increased in ANP group, the expressions of PTHI R decreased significantly. Compared with ANP group, the activity of NF-κB decreased and the levels of PTH1R and serum calcium increased in PDTC group (P<0.05). Conclusions NF-κB may indirectly down-regulate the expression of PTH1R, which resulting into the hypocalcaemia of ANP. PDTC may alleviate hypocalcaemia in ANP.