左旋精氨酸在急性胰腺炎治疗中的剂量效应

DOSE-DEPENDENT ROLE OF L-ARGININE IN TREATMENT OF ACUTE PANCREATITIS IN RATS

目的:探讨左旋精氨酸(L-Arg)在急性胰腺炎治疗中的剂量效应。方法:观察不同剂量L-Arg治疗急性水肿性胰腺炎(AEP)大鼠后,血浆和胰组织一氧化氮(NO)浓度、血浆淀粉酶、平均动脉压(MAP)、胰组织病理等的变化。结果:(1)AEP大鼠血浆、胰组织NO浓度明显降低,小剂量L-Arg(50mg,100mg/kg)升高了血浆、胰组织NO浓度,改善了大鼠AEP;随着L—Arg剂量的增加,达800mg、1600mg/kg时,血浆、胰组织NO浓度过度升高,加重AEP成为急性出血坏死性胰腺炎(AHNP),且以80mg/kg组最明显;(2)实验所用的L—Arg对MAP的影响较小。结论:L—Arg的作用机理与NO的生物学行为有密切关系,临床应用L-Arg治疗急性胰腺炎应注意其类似NO的“双刃性”,尤其大剂量应用要慎重。

Objective:To research the role of different doses of L-arginine in the therapy of acute pancreatitis in Sprague -Dawley (SD) rats. Method: 80 SD rats were divided equally into eight groups, i. e. normal group, acute edematous pancreatitis (AEP) model group and six treatmental groups of AEP model treated with six doses of L -arginine. AEP model was induced by 10μg/kg caerulein for two hours with one hour interval. Lipopolysaccharide pretreatment was given at the third hour, and then six treatmental groups were injected with different doses of L-arginine at the beginning of the fourth hour. Alterations of mean arterial pressure (MAP), plasmic amylase. nitric oxide in plasma and pancreatic tissues, and pancreatic pathohistology were studied at the ending of the fourth hour. Result: Concentration of nitric oxide in plasma and tissues decreased. 50 to 100 mg/kg L - arginine (800 to 1600mg/kg) caused acute hemorrhage and necrotizing pancreatitis. MAP of most treatmental groups decreased and plasmic amylase increasd significantly, but these alterations were not related to the scores of pancreatic pathohistology. Conclusion : It is suggested that low dose of L - arginine can be used to treat acute pancreatitis, but the high dose of L - arginine should be used carefully.