NF—kB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

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

目的探讨NF—kB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6h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-kB、PTH1R蛋白表达，RT-PCR检测肾脏和骨组织PTH1RmRNA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—kB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PTH1RmRNA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—kB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—kB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—kB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。

Objective To investigate the effect of nuclear factor-kappa B（NF-kB） 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-kB） pretreated ANP group （PDTC）, with 8 rats each group. ANP model was induced by injecting 5% sodium taurodeoxycholate into biliary pancreatic duct. Serum calcium was measured and the expression of NF-kB 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-KB 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-KB increased in ANP group, the expressions of PTH1R decreased significantly. Compared with ANP group, the activity of NF-kB decreased and the levels of PTH1R and serum calcium increased in PDTC group （ P 〈 0.05 ）. Conclusions NF-kB may indirectly down-regulate the expression of PTH1R, which resulting into the hypocalcaemia of ANP. PDTC may alleviate hypocalcaemia in ANP.