p38丝裂原活化蛋白激酶对急性坏死性胰腺炎大鼠低钙血症的影响

目的 探讨p38丝裂原活化蛋白激酶(p38MAPK)信号转导通路对急性坏死性胰腺炎(ANP)大鼠低钙血症和甲状旁腺激素受体1(PTHR1)表达的影响.方法 将雄性SD大鼠72只按完全随机法分为ANP组、SB203580干预(SB)组和假手术(SO)组,每组分3、6、12 h 3个时间点,每个时间点8只.以5%牛磺脱氧胆酸钠逆行胰胆管注射建立ANP模型,SB组在造模前30 min腹腔注射p38MAPK特异抑制剂SB203580 10 mg/kg体重.观察各组血清钙浓度,蛋白质印迹法(Western blotting)分析骨组织磷酸化p38MAPK(P-p38 MAPK)和TNF-α变化,实时RT-PCR检测骨组织PTHR1 mRNA表达.结果 制模后6 h,SO组、ANP组和SB组血清钙浓度分别为(2.50±0.08)mmoL/L、(2.11±0.06)mmol/L和(2.35±0.10)mmol/L;骨组织P-p38 MAPK表达量分别为0.14±0.04、0.80±0.06和0.33±0.05;骨组织TNF-α表达量分别为0、0.91±0.04和0.44±0.03;骨组织PTHR1 mRNA表达量分别为1.00±0.12、0.23±0.04和0.44±0.06.SB组骨组织P-p38 MAPK及TNF-α表达较ANP组显著降低(P＜0.01);骨组织PTHR1 mRNA表达量及血清钙浓度较ANP组显著增加(P＜0.01).结论 p38MAPK信号转导通路可介导ANP低钙血症的发生,抑制该通路可改善ANP低钙血症.

Effect of p38 mitogen-activated protein kinase on hypocalcaemia of rats with acute necrotizing pancreatitis

Objective To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in hypocaleaemia and parathyroid hormone receptor 1 ( PTHR1 ) of rats with acute necrotizing pancreatitis (ANP).Methods Seventy-two male health adult Spragne-Dawley rats were randomized into three groups:ANP group,ANP treated with SB203580 group (SB group),sham operation group (SO group).Every group was sub-divided into 3,6,12 h group with 8 rats in each one.ANP model was induced by retrograde infusion with 5% sodium taurocholate solution into the biliopancreatie duct.In the SB group,rats were treated with the specific p38MAPK inhibitor:SB203580 30 minutes before the induction of ANP model.The serum level of calcium was determined,the change of phosphorylated p38MAPK and TNFalpha were measured by western blot and the expression of PTHR1 mRNA was determined by quantitative real time RT-PCR.Results 6 h after ANP model induction,the serum levels of calcium in ANP,SB and SO group were (2.50±0.08 ) mmol/L,(2.11±0.06 ) mmol/L and (2.35±0.10 ) mmol/L,respectively;the expression levels of pbosphorylated p38MAPK in bone tissue were 0.14±0.04,0.80±0.06 and 0.33±0.05,respectively;the expression levels of p38MAPK TNF-alpha were 0,0.91±0.04 and 0.44±0.03,respectively;the expression levels of PTHR1 mRNA were 1.00±0.12,0.23±0.04 and 0.44±0.06,respectively.The expression levels of p38MAPK and TNF-α in SB group were significantly lower than those in the ANP group (P ＜ 0.01 );while the expression levels of PTHR1 mRNA and calcium were significantly higher than those in the ANP group (P ＜0.01 ).Conclusions P38MAPK signal transduction pathway may mediate the development of hypocaleaemia in the course of ANP,and hypoealcaemia could be improved by blocking this pathway.