不同剂量坎地沙坦治疗大鼠急性胰腺炎的实验研究

Treatment with different doses of candesartan in acute pancreatitis model

目的:探讨选择性血管紧张素Ⅱ受体亚型AT1拮抗剂坎地沙坦不同剂量对大鼠急性胰腺炎(AP)的影响。方法:72只雄性SD大鼠随机分为正常对照组、AP组、AP+低剂量坎地沙坦组(2 mg/kg)、AP+高剂量坎地沙坦组(10 mg/kg)。腹腔注射20%L-精氨酸溶液建立AP动物模型;坎地沙坦用大鼠灌胃针灌注。各组大鼠分别在造模后12 h、24 h、48 h分批次等数量(6只/组/批)心脏取血处死。取胰腺组织观察胰腺病理变化并评分(按Rongione标准),胰腺/体质量比,检测大鼠血清脂肪酶、TNF-α、IL-10的变化。结果:AP组胰腺炎症评分,胰腺/体质量比,血清脂肪酶、TNF-αI、L-10较对照组明显升高(P<0.01)。其中胰腺/体质量比于造模后12 h已有明显升高,于48 h达到高峰;而血清脂肪酶和胰腺TNF-αI、L-10于造模后12 h达到高峰,此后有所下降,但仍然保持较高水平。坎地沙坦干预的实验组胰腺炎症评分,胰腺/体质量比,血清脂肪酶、TNF-α以及胰腺TNF-α较AP组降低(P<0.05),但低剂量坎地沙坦组与高剂量组间无显著差异(P>0.05)。本实验中,应用坎地沙坦对AP大鼠血清及胰腺IL-10均无显著影响(P>0.05)。结论:应用AT1受体拮抗剂坎地沙坦可以明显减轻L-精氨酸诱导大鼠急性胰腺炎的炎症及损伤。

Objective： To investigate the selective AT1 subtype angiotensin Ⅱ receptor antagonist candesartan dose on acute pancreatitis（acute pancreatitis,AP） effect.Methods： 72 male SD rats were randomly divided into normal control group,AP group,AP ＋ low-dose candesartan group（2 mg/kg）,AP＋candesartan high dose group（10 mg/kg）;intraperitoneal injection of 20% L-arginine solution established animal model of AP;candesartan in rats fed with needle perfusion.Rats in each group,respectively 12,24,48 hours after modeling the number of batches,（6/group/batch） heart blood to death.Pancreas tissue and pathological changes of pancreas were observed score（by Rongione standard）,pancreas/ body weight ratio,serum lipase test,TNF-α,IL-10 changes.Results： AP group disease score pancreatitis,pancreatic/ body weight ratio,serum lipase,TNF-α,IL-10 was significantly higher than the control group（P〈0.01）.Pancreas/body weight ratio in the 12 hours after modeling has been significantly increased,then the peak at 48 hours;the serum lipase and pancreatic TNF-α,IL-10 in the 12 hours after the model peak,then decline,but still maintain a high level.Candesartan pancreatitis patients in the experimental group intervention score,pancreas / body weight ratio,serum lipase,TNF-α and TNF-α pancreatic lower than the AP group（P〈0.05）,but low dose candesartan group and high dose no significant difference between groups（P〈0.05）.In this study,the application of candesartan on serum levels of AP and pancreatic IL-10 had no significant effect（P〉0.05）.Conclusion： AT1 receptor antagonist candesartan can significantly reduce the L-arginine induced acute pancreatitis in inflammation and injury.