School of Pharmacy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jiangsu, China.
Indian J Pharmacol. 2012 Jan;44(1):31-5. doi: 10.4103/0253-7613.91863.
This study was designed to investigate the gastroprotective effect of L-citrulline against gastric ischemia-reperfusion injury.
Sodium pentobarbital-anesthetized rats underwent occlusion of the celiac artery for 30 min, followed by 60 min of reperfusion. Sixty minutes before ischemia, L-citrulline at doses of 300, 600, 900 mg/kg was administered intragastrically. Based on this animal model of gastric ischemia-reperfusion injury, the gastroprotective effect of L-citrulline was assessed by determining and comparing the ulcerative index and the estimation of myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the gastric mucosal tissues. Moreover, the expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) protein was also determined.
Intragastric administration of L-citrulline (600 and 900 mg/kg) 60 min before ischemia significantly ameliorated the gastric mucosal damage and inhibited the increase in MPO and MDA contents. Also, the increase in expression of iNOS protein was also prevented by L-citrulline. The expression of nNOS and eNOS was not affected significantly by I/R or L-citrulline.
The results suggest that L-citrulline, administered exogenously, exhibits gastric protection by inhibition of neutrophil infiltration in rats, which may be related in prevention of the increase in iNOS activity.
本研究旨在探讨左旋瓜氨酸(L-citrulline)对胃缺血再灌注损伤的胃保护作用。
采用腹部麻醉的大鼠,夹闭腹腔动脉 30 分钟,然后再灌注 60 分钟。在缺血前 60 分钟,通过灌胃给予左旋瓜氨酸,剂量分别为 300、600、900mg/kg。基于这种胃缺血再灌注损伤的动物模型,通过测定和比较溃疡指数、胃黏膜组织髓过氧化物酶(MPO)活性和丙二醛(MDA)水平来评估左旋瓜氨酸的胃保护作用。此外,还测定了诱导型一氧化氮合酶(iNOS)、神经元型一氧化氮合酶(nNOS)和内皮型一氧化氮合酶(eNOS)蛋白的表达。
缺血前 60 分钟给予左旋瓜氨酸(600 和 900mg/kg)可显著改善胃黏膜损伤,并抑制 MPO 和 MDA 含量的增加。左旋瓜氨酸还可预防 iNOS 蛋白表达的增加。nNOS 和 eNOS 的表达不受 I/R 或左旋瓜氨酸的显著影响。
这些结果表明,外源性给予左旋瓜氨酸可通过抑制大鼠中性粒细胞浸润来发挥胃保护作用,这可能与预防 iNOS 活性增加有关。