Hogaboam C M, Collins S M, Blennerhassett M G
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada.
Am J Physiol. 1996 Aug;271(2 Pt 1):G338-46. doi: 10.1152/ajpgi.1996.271.2.G338.
We investigated the involvement of nitric oxide in transmural jejunal alterations induced by Trichinella spiralis (T. spiralis) infection in rats. Rats were gavaged with either saline or T.spiralis larvae, and, 1 h later, rats were treated orally with water, NG-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), or NG-nitro-D-arginine methyl ester (D-NAME; 30 mg/kg) on a daily basis. Although not observed in jejunum from uninfected rats, inducible nitric oxide synthase (iNOS) mRNA was present in the mucosa and neuromuscular layers of jejunum from T. spiralis-infected rats. On day 6, T. spiralis-infected rats had a 6-fold decrease in transmural nitric oxide synthase activity, an 11-fold increase in plasma nitrite, and a 7-fold elevation in transmural myeloperoxidase (MPO) activity compared with uninfected controls. Intestinal smooth muscle cell hyperplasia and hypertrophy were only detected in the infected rats. L-NAME, but not D-NAME, treatment of infected rats for 6 days caused a pronounced increase in transmural iNOS mRNA expression, coinciding with significantly increased mucosal nitric oxide synthase activity. T. spiralis numbers in L-NAME-treated rats were significantly lower compared with the other two infected groups although L-NAME had no direct effect on T. spiralis viability in vitro. Furthermore, L-NAME treatment significantly reduced plasma nitrite and jejunal MPO but not intestinal smooth muscle cell hyperplasia or hypertrophy. In contrast, D-NAME treatment of infected rats significantly enhanced intestinal smooth muscle hyperplasia and hypertrophy. Taken together, these results suggest that alterations in the T. spiralis-infected jejunum are mediated, in part, by a suppression of nitric oxide synthase activity in the inflamed jejunum.
我们研究了一氧化氮在旋毛虫感染大鼠所致空肠全层改变中的作用。给大鼠灌胃生理盐水或旋毛虫幼虫，1小时后，每天给大鼠口服水、NG-硝基-L-精氨酸甲酯（L-NAME；30mg/kg）或NG-硝基-D-精氨酸甲酯（D-NAME；30mg/kg）。虽然在未感染大鼠的空肠中未观察到，但诱导型一氧化氮合酶（iNOS）mRNA存在于旋毛虫感染大鼠空肠的黏膜和神经肌肉层中。在第6天，与未感染对照组相比，旋毛虫感染大鼠的空肠全层一氧化氮合酶活性降低了6倍，血浆亚硝酸盐增加了11倍，空肠全层髓过氧化物酶（MPO）活性升高了7倍。仅在感染大鼠中检测到肠道平滑肌细胞增生和肥大。用L-NAME而非D-NAME处理感染大鼠6天，导致空肠全层iNOS mRNA表达显著增加，同时黏膜一氧化氮合酶活性显著增加。与其他两个感染组相比，L-NAME处理的大鼠体内旋毛虫数量显著减少，尽管L-NAME在体外对旋毛虫活力没有直接影响。此外，L-NAME处理显著降低了血浆亚硝酸盐和空肠MPO，但未减轻肠道平滑肌细胞增生或肥大。相比之下，用D-NAME处理感染大鼠显著增强了肠道平滑肌增生和肥大。综上所述，这些结果表明，旋毛虫感染所致空肠的改变部分是由炎症空肠中一氧化氮合酶活性的抑制介导的。
