异搏定对胰腺腺泡细胞内游离钙离子浓度的影响

目的:探讨细胞内钙超负荷在急性胰腺炎(AP)发生发展中的作用.方法:使用140只SD大白鼠胆胰管逆行加压注射4.5%牛磺胆酸钠制成AP模型,用荧光指示剂Fura-2/Am测定游离胰腺腺泡细胞内游离钙离子浓度(Ca~(2 )]i).结果:注射后2小时和3小时胰腺呈急性出血坏死性炎症早期改变,制AP模型后AP组Ca~(2 )]i较对照组明显增高(P<0.001),AP组胰腺腺泡细胞内Ca~(2 )]i增高值与胰腺病理变化程度呈正相关关系(r_s=0.9727,P<0.001),异搏定治疗可明显提高病鼠生存率和改善胰腺组织出血坏死程度和腺泡细胞超微结构损害.结论:胰腺腺泡细胞内钙超负荷在胆汁性急性水肿性胰腺炎向出血坏死性胰腺炎转变中起明显作用,钙通道阻滞剂异搏定可明显阻止胰腺细胞内钙离子超负荷,是其治疗急性胰腺炎的主要机理之一.

The role of cell calcium overload in the conversion of edematous to necrotizing pancreatitis: Effects of verapamil on cytosolic free calcium of rat pancreatic acini

Experimental acute pancreatitis (AP) was inducted by biliopancreatic retrograde injection of 4.5% sodum taurocholate solution (0. 1ml/100g) in 140 SD rats. In the treated group, a dose of 0.1mg (0.25ml/100g) verapamil was given intraperitoneally at 5min after inductoion of AP. Morphological changes of pancreas were examined by histological and ultra-structural techniques, and the intracellular free calcium concentration (Ca2 ]i) of pancreatic acinar cells measured by Shimazu 5000-RF fluorescence spectropho-tometer in the three groups. The results demonstrated that early changes of acute necrostic-haemorrhagic pancreatitis were observed 2 and 3h after AP. The pancreatic acinar cellCa2 ]i was increased from sham-operated control to its highest at 2 h after induced AP in the AP group (P<0. 001). In the treated group, the pancreatic acinar cellCa2 ]i was lower than that in AP group significantly (P<0. 001). It was found there was a positive relationship between the pancreatic acinar cell Ca2 ] i and the severity of pancreatic damage (r = 0.9227, P<0. 001) in the AP group. The treatment of verapamil can significantly increase the survival rate and prolong the survival time, decrease the severity of pancreatic hemorrhage and necrosis and the damages to the pancreatic cellular ultrastructures in the AP rats. These data suggest that in the early stage of AP, the cell calcium overload might play a key role in the pathophysiology of bile-induced AP in rats: Verapamil could obviously prevent the overload of the cell calcium, which was one of the main mechanims for the treatment of AP.