丹参和氢化可的松对重症急性胰腺炎大鼠三磷酸肌醇及钙代谢的影响

Influence of Danshen and glucocorticoid on inositol triphosphate and calcium metabolism in rats with severe acute pancreatitis

目的:观察重症急性胰腺炎(SAP)动物模型三磷酸肌醇(IP3)的变化及与钙代谢的关系和丹参及糖皮质激素的影响。方法:50只SD大鼠随机分5组:SAP模型组(SAP组)、丹参治疗组(A组)、氢化可的松治疗组(B组)、丹参加氢化可的松治疗组(AB组)和对照组(C组),各10只。SAP组逆行胰胆管注射3%牛磺胆酸钠建立SAP模型,C组则注射生理盐水(NS)。SAP组和C组术后行阴茎背静脉注射NS;A组、B组和AB组如SAP组一样建立模型,术后分别注射丹参、氢化可的松、丹参加氢化可的松。18 h后,观察各组胰腺细胞IP3和细胞内钙(Ca2+)、血清肿瘤坏死因子α(TNF-α)、血清钙(血钙)和淀粉酶(AMY),以及胰腺的病理改变。结果:SAP组IP3、Ca2+、TNF-α、AMY和胰腺病理评分(PSP)显著高于A组、B组、AB组和C组(p<0.05),其中AB组明显低于A组和B组(p<0.05),但A、B组间无明显差异(p>0.05);C组的PSP明显低于A组、B组和AB组(p<0.05),C组的IP3和Ca2+明显低于AB组(p<0.05),AB组与C组的TNF-α间无明显差异(p>0.05);IP3与Ca2+,IP3与TNF-α间呈明显正相关(r分别为0.987和0.937,p<0.05);血钙则是SAP组显著低于A组、B组、AB组和C组(p<0.05),AB组和C组分别明显高于A组和B组(p<0.05),AB组显著低于C组(p<0.05),但A组与B组间无明显差别(p>0.05)。IP3、Ca2+和TNF-α与血钙为负相关(r分别为-0.997、-0.980和-0.915,p<0.05)。结论:SAP大鼠胰腺细胞IP3显著升高;IP3与Ca2+和TNF-α水平呈明显正相关,前三者与血钙呈负相关,IP3可能是引起细胞内外钙和TNF-α变化的重要原因之一;丹参和糖皮质激素均可抑制SAP大鼠胰腺细胞IP3和Ca2+及TNF-α的释放,促进血钙水平回升,胰腺组织病理损害减轻,联合使用丹参和氢化可的松具有协同作用。

Objective：To investigate the changes of inositol triphosphate（IP3） and the relation between the IP3 and calcium metabolism,and the effect of Danshen and glucocorticoid on the change in rats with severe acute pancreatitis（SAP）.Method：Fifty Sprague-Dawley rats were randomly divided into fi ve groups：severe acute Pancreatitis group（group SAP）,treatment group of Danshen（group A）,treatment group of dermacort（group B）,Danshen and dermacort treatment group（group AB）,and control group（group C）.The model of SAP was induced by 3% Sodium Taurocholate.After operation,normal sodium（NS） was injected by vena in group SAP and C.However the group C was ham operation.The model of group A,B and AB were established as group SAP.But Danshen were administered in group A and dermacort in group B,the integrated Danshen and dermacort were used in group AB.Serum amylase（AMY）,calcium and tumor necrosis factor α（TNF-α） were examined.Intracellular IP3 and Ca^2＋,and histological change and pathological scores of pancreas（PSP）were observed after 18 h.Result：The IP3,Ca^2＋,TNF-α,AMY and PSP in group SAP were signifi cantly higher than those in group A,group B,group AB and group C（p〈0.05）.And those in group AB were significantly lower than those in group A and group B（p〈0.05）,but there were not signifi cantly different between group A and group B（ p〉0.05）.The PSP in group C were signifi cantly lower than those in group A,group B and group AB（p0.05）,but the IP3 and Ca^2＋ in group C were signifi cantly lower than those in group AB.There were not signifi cantly different of TNF-α between group AB and group C.The IP3 of pancreas was positive correlation with Ca^2＋and TNF-α and negative relation with the serum calcium in SAP（r = 0.987,r = 0.937,p0.05）.Serum calcium in group SAP were significantly lower than those in group A,group B,group AB and group C（p0.05）,however that in group AB and group C were signifi cantly higher than those in group A group B.Serum calcium in group AB was signifi cantly lower than those in group C,but there were not signifi cantly different between group A and group B.IP3,Ca^2＋ and TNF-α were negative related with the serum calcium in SAP（r=-0.997、-0.980和-0.915,p0.05）.Conclusion：There are signifi cantly increase of the pancreatic cell IP3,and the increase of IP3 is positive related with the Ca^2＋ and TNF-α.And IP3,Ca^2＋ and TNF-α are negative related with the serum calcium in SAP.It show that the IP3 is a main factor inducing abnormity of calcium metabolism in SAP.Danshen and glucocorticoid may respectively restrain the release of IP3,however the effects of both medicine integration is better than single medicine.