EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE IN PORTAL HYPERTENSION RATS

• Main Authors: Shen-Tsusen Lian, 連紳村
• Other Authors: Shiu-Ru Lin ph.D
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/78195050848101272386

碩士 === 高雄醫學大學 === 醫學研究所 === 90 === In patients with liver cirrhosis, gastrointestinal bleeding related to portal hypertension may be caused by either rupture of esophageal vasices or acute gastric mucosal lesions. Because gastric mucosa has distinct, morphologic and functional abnormalities that increase its susceptibility to damage by noxious factors and ischemia/reperfusion, it has been indicated as the main cause of congestive gastropathy. Clinical observations suggested that PHT itself induced gastric mucosal lesions, which predispose them to damage and hemorrhage, however, its molecular mechanism has not yet been completely understood. It has been suggested that overproduction of endogenous vasodilator, and reduced vascular sensitivity to endogenous vasoconstrictors may contribute to these circulatory disturbances. Recently, increased biosynthesis of nitric oxide ( NO ) has been implicated in our previous study showed that in the hyperdynamic circulation due to its vasodilatory effects. Whether the lesions of PHT gastric mucosal were also caused by the increase of NOS activity and NO products needs to be investigated. The aim of this study was to determine whether the overexpression of inducible NOS and increase of NO production are responsible for PHT gastropathy. Furthermore, the correlation between the expression of inducible NOS and the gastric mucosal lesions was also analyzed. First, we used Northern blot hybridization to compare expression of gastric mucosal inducible NOS mRNA in the PHT rats and the controls. The density ratios of inducible NOS mRNA were remarkably higher in PVL rats than the control ( p<0.05 ). Moreover, in situ hybridization was also performed to identify which cells expressed inducible NOS mRNA in the gastric mucosa. The results revealed the inducible NOS mRNA significantly expressed in the mucous neck cell of PVL rats. Immunohistochemical staining was used for the determination of inducible NOS protein expression. The results showed that the amount of inducible NOS protein was higher in the PVL group than the control group ( p<0.05 ). After the administration of NOS inhibitor, the NO product was decreased, and the changes of gastric mucosal lesions were evaluated. The expression of inducible NOS mRNA was reduced by NOS inhibtor with improvement of gastric mucosal lesions , the defense mechanisms of NOS in PHT could be understood more clearly. The above results indicated a novel defense mechanism of inducible NOS in PHT gastric mucosa. We hope this can be useful in the prevention and treatment of PHT gastropathy.