The Molecular Mechanism Of Tumor Necrosis Factor α Induced Hypocalcemia In Severe Acute Pancreatitis Rats.

Objective To investigate the correlation and the molecular mechanismbetween serum Tumor Necrosis Factor α(TNF-α)and the hypocalcemia of severeacute pancreatitis (SAP).Methods SAP animal model was developed in adult male rats by retrogradeinjection of 5% sodium taurocholate. Sixty-three male Sprague-Dawley ratswere divided into sham operation(n=21),SAP group(n= 21),SAP therapygroup(n=21).In SAP therapy group ,TNF-αMcAb(5mg/kg) was infusedintravenously 15 minutes before acute pancreatitis was induced. The levelof serum TNF-α,calcium and parathyroid hormone receptor(PTHR)mRNA weretested in different time. TNF-αwas determined by ELISA. Expression of PTHRmRNA in the bone and kidney were detected by RT-PCR.Results The generation of TNF-αhad a close relation to the level of serumcalcium in the SAP(r=-0.69 P<0.01),especially at the initial stage (6hour r=-0.73 P<0.01).The serum calcium level in the groups of SAP was (1.99±0.03)mmol/L and (1.88±0.05)mmol/L respectively 6 and 12h after SAP onset.The serum TNF-αlevel in the groups of SAP was (179.36±6.35)pg/ml and(225.43±7.94)pg/ml respectively 6 and 12h after SAP onset. As compared withsham operation groups, the level of serum calcium and the expression ofPTHR mRNA in bone and kidney in the SAP rats were significantlydecreased(P<0.1),the level of serum TNF-αin the SAP rats was significantlyelevated(P<0.1). With TNF-αMcAb pretreatment, the pancreatic pathologicalchange was alleviative and serum amylase, serum TNF-αwere significantlyreduced. The serum calcium level in the groups of TNF-αMcAb pretreatmentwas (2.06±0.06)mmol/L and (1.94±0.05)mmol/L respectively 6 and 12h afterSAP onset. The serum TNF-αlevel in the groups of TNF-αMcAb pretreatmentwas (86.61±0.87)pg/ml and (127.89±9.53)pg/ml respectively 6 and 12h afterSAP onset. Compared with SAP groups, the level of serum calcium and theexpression of PTHR mRNA in bone and kidney in the TNF-αMcAb pretreatmentrats were significantly elevated (P<0.5), the level of serum TNF-αin theTNF-αMcAb pretreatment rats was significantly decreased (P<0.1).Conclusions TNF-αmay via blocking the expression of PTHR mRNA in boneand kidney and decreasing the function of PTH to cause hypocalcemia in SAP.