络沙坦对急性坏死性胰腺炎保护作用的实验研究

Protective effect of Losartan, an angiotensin Ⅱ receptor antagonist, on acute necrotic pancreatitis.

目的研究络沙坦(Losartan)对急性坏死性胰腺炎(ANP)大鼠是否有保护作用。方法SD大鼠40只,随机分为4组:正常对照组、ANP组、Losartan预防组、Losartan治疗组。采用大剂量精氨酸腹腔注射诱导ANP模型,预防组于造模前90min给予Losartan200μg/kg体重,两次,间隔1h,治疗组于造模后30min给予Losartan200μg/kg体重,两次,间隔1h。各组于造模后24h处死大鼠,观察大鼠血浆血管紧张素(Ang)、肾素(PRA)、淀粉酶(AMY)、TNF-α、IL-1β变化,RT-PCR法检测胰腺组织血管紧张素原、肾素及Ang受体AT1mRNA的水平,检测胰腺/体重比,观察胰腺组织病理变化。结果ANP组Ang、PRA、AMY、TNF-α、IL-1β、胰腺/体重比值较对照组明显升高;胰腺组织血管紧张素原、肾素和AT1mRNA的水平也较对照组升高,Losartan预防组和治疗组血浆AMY、TNF-α、IL-1β较ANP组明显下降,胰腺组织病理损伤明显减轻,但Ang、PRA变化不明显。结论络沙坦对血浆Ang、PRA及血管紧张素原、肾素和AT1mRNA无明显影响,可以减少TNF-α、IL-1β的产生,对ANP具有保护作用。

Objective To investigate the protective effect of losartan on acute necrotic pancreatitis（ANP） in rats. Methods Forty SD rats were randomly divided into 4 groups： control group, ANP group, losartan preconditioned group, and losartan treatment group. The ANP model was induced by intraperitoneal injection of L-arginine. Rats in losartan preconditioned group were injected with 200 μg/kg losartan twice hourly 90 min before induction of ANP. Rats in losartan treatment group was injected with losartan 200μg/kg twice hourly 30 minutes after the induction of ANP. All rats were killed 24 h after induction of ANP and the levels of angiotensin Ⅱ , renin, amylase, TNF-α, IL-1β in blood, and the ratio of pancreatic weight to body weight were measured. The mRNA of angiotensinogen, rennin and angiotensin Ⅱ receptor ATI were analyzed by RT-PCR. Histopathological changes of pancreas were also observed. Results Compared with control group, the levels of angiotensin Ⅱ . renin, amylase. TNF-α . IL-1β in plasma and the ratio of pancreatic weight to body weight were all significantly increased in ANP group： and mRNA expression of angiotensinogen, rennin, and angiotensin Ⅱ receptor ATI were also increased. Compared with the ANP group, the levels of AMY, TNF-α, and IL-1β in both losartan preconditioned group and treatment group were significantly reduced, but the levels of angiotensin Ⅱ and rennin had no obvious changes, Losartan also ameliorated the pancreas histopathologic inflammation. Conclusions Losartan has no obvious influence on plasma Ang Ⅱ, PRA, angiotensinogen, rennin, and AT1, but can decrease the production of TNF-α and IL-1β, thus protecting patients with ANP.