银杏苦内酯B治疗大鼠急性坏死性胰腺炎量效关系的实验研究

The research of dose-effect of Ginkgolide B on rats with severe acute pancreatitis.

目的探讨银杏苦内酯B（BN52021）治疗大鼠ANP的最佳量效关系。方法70只雄性Wistar大鼠随机分为假手术组（SO组）,ANP组,二甲基亚砜对照组（DMSO组）,BN520212.5mg、5mg、10mg/kg体重治疗组（BN1、BN2、BN3组）,善宁20μg/kg体重治疗组（SS组）共7组。胰胆管逆行注射5%牛磺胆酸钠制备ANP模型。SO组、DMSO组和BN治疗组分别于术后15min股静脉注射等量生理盐水、0.5%DMSO和不同浓度的BN52021,SS组皮下注射善宁。各组分别于制模后6h取血检测血清淀粉酶和磷脂酶A2（PLA2）含量,记录腹水量,取胰腺组织行病理学检查和检测血小板活化因子受体（PAF-R）mRNA表达。结果ANP组和DMSO组血清淀粉酶、PLA2、腹水量、胰腺病理分值较SO组显著升高（P〈0.05）,各治疗组较ANP组显著降低（P〈0.05）,且BN2组血清淀粉酶、PLA2含量的降低又较BN1、BN3和SS组更显著（P〈0.05）。ANP组胰腺组织PAF-RmRNA表达较SO组显著降低（P〈0.05）,各治疗组较ANP组显著升高（P〈0.05）,而各治疗组间无显著差异。结论静脉注射BN520215mg/kg体重治疗ANP大鼠具有最佳的量效关系。

Objective To explore optimal dose of Ginkgolide B on rats with acute necrotizing pancreatitis （ANP）. Methods 70 male Wistar rats were randomly divided into seven groups： Sham operation group（SO group, n = 10）, ANP model group （ANP group, n = 10）, DMSO contrast group （DMSO group, n = 10）, 2.5 mg/kg BN52021 treatment group （BN1 group, n = 10）, 5 mg/kg BN52021 treatment group （BN2 group, n = 10）, 10 mg kg BN52021 treatment group （BN3 group, n = 10）, and 20μg/kg sandostatin treatment group（SS group, n = 10）. The model of ANP was established in Wistar rats by injecting 5 % sodium taurocholate retrogradely into the common pancreatico-biliary duct. The rats of SO, DMSO, and BN52021 treatment group were injected respectively the same quantity of 0. 9% NaCl, 0.5 %DMSO, and different concentration BN52021 by femoral vein in 15 min after the operation. The rats of SS group were injected sandostatin subcutaneously. The rats in each group were anaesthetized at 6 hours after the operation, and venous blood was collected to detect the levels of serum amylase and PLA2, and pancreas tissue was harvested and stained for observing and scoring. The quantity of ascites was collected and measured. The levels of platelet activating factor receptor （PAFR） mRNA of pancreas tissue were investigated by RT-PCR. Results The results of the serum amylase, PLA2, ascites, pathologic score showed that there were not significantly different between ANP and DMSO groups, and they were significantly higher in ANP and DMSO groups than those in SO group （P 〈0.05） ; and they were lower in BN1, BN2, BN3 and SS groups than those in ANP group （P 〈 0.05）. However, the BN2 had the best effect in decreasing the level of serum amylase and PLA2 as compared with among BN1, BN2, BN3 and SS groups （P 〈 0.05）. Expressions of PAFR mRNA and its proteins showed that there were significantly difference between ANP and SO groups （P 〈 0.05）, the expressions of PAFR mRNA in ANP group were significantly higher than those in other groups （P 〈 0.05）, while there were not significantly difference among the treatment groups. Conclusions The 5 mg/kg of Ginkgolide B by intraveinous injection was the optimal dosage in treating rats with ANP.