静脉注射罗格列酮治疗大鼠急性胰腺炎的量效关系

目的:探讨罗格列酮(ROSI)静脉给药治疗大鼠急性胰腺炎(AP)的量效关系。方法:雄性Wistar大鼠42只,随机分为7组(n=6):假手术组(SO组)、急性胰腺炎组(AP组)、ROSI 0.3,3,6,10 mg/kg预处理组和药物对照组。胆胰管逆行注射5%牛磺胆酸钠制备AP模型。SO组、AP组造模前30 min股静脉注射10%二甲基亚砜(DMSO)(2 ml/kg),不同剂量预处理组则注射等量、10%DMSO溶解的ROSI。术后12 h心脏取血检测各组血清淀粉酶(AMY)、谷氨酸氨基转移酶(ALT)变化,观察胰腺组织病理学改变。药物对照组根据ROSI干预效果选择最佳剂量,造模前30 min股静脉注射最佳剂量的ROSI取代10%DMSO。术后12 h检测其血清AMY、ALT及胰腺组织病理学改变。结果:与AP组比较,0.3,3 mg/kg ROSI预处理组AMY、ALT没有改变,胰腺组织病理学评分有所改善(P<0.05);6 mg/kg ROSI预处理组上述指标较AP组显著降低(P<0.01),10 mg/kg ROSI预处理组AMY、胰腺组织病理学评分较AP组显著降低(P<0.01),但ALT与AP组比较差异无统计学意义(P>0.05)。药物对照组(6 mg/kg)上述指标与SO组比较差异无统计学意义(P>0.05)。结论:针对胆胰管逆行注射牛磺胆酸钠制备的大鼠AP模型,6 mg/kg静脉注射罗格列酮是安全、有效的剂量。

Dose-Response Relationship of Rosiglitazone on Acute Pancreatitis in Rats

Objective: To investigate the dose-response relationship of rosiglitazone on acute pancreatitis in rats.Methods: Forty-two male Wistar rats were randomly divided into seven groups(n=6): sham operation group(SO group),acute pancreatitis model group(AP group),rosiglitazone pretreatment groups at different dosage(0.3,3,6 and 10 mg/kg) and drug control group(dosage according to the effect of rosiglitazone).AP model was induced by retrograde infusion of 5% sodium taurocholate(1 ml/kg) into the biliopancreatic duct.The rats of SO group and AP group were injected with 10%DMSO(2 ml/kg)by femoral vein 30 min before the operation.Drug control group was injected rosiglitazone instead of 10% DMSO.Rats were killed at 12 h after operation.Blood samples were obtained for detecting serum amylase and alanine aminotransferase.Pancreatic tissue samples were stained with hematoxylin and eosin for pancreatic histopathological evaluation.Results: Compared with AP group,0.3 mg/kg and 3 mg/kg dosage failed to improve the levels of amylase and alanine aminotransferase,but attenuated severity of pancreatic injury(P<0.05).6 mg/kg dosage had the best effect on improving the levels of amylase and alanine aminotransferase and pathologic scores(P<0.01).The dosage of 10mg/kg also improve the level of amylase and pathologic scores(P<0.01),but failed to improve the level of alanine aminotransferase(P>0.05).Conclusion: Rosiglitazone(6 mg/kg) administered intravenously was the optimal dosage for attenuating the severity of acute pancreatitis induced by retrograde infusion sodium taurocholate.