Baccari M C, Nistri S, Vannucchi M G, Calamai F, Bani D
Department of Physiological Sciences, University of Florence, V.le G.B. Morgagni 63, I-50134, Florence, Italy.
Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R662-8. doi: 10.1152/ajpregu.00214.2007. Epub 2007 May 23.
Altered nitric oxide (NO) production/release is involved in gastrointestinal motor disorders occurring in dystrophic (mdx) mice. Since the hormone relaxin (RLX) can upregulate NO biosynthesis, its effects on spontaneous motility and NO synthase (NOS) expression in the ileum of dystrophic (mdx) mice were investigated. Mechanical responses of ileal preparations were recorded in vitro via force-displacement transducers. Evaluation of the expression of NOS isoforms was performed by immunohistochemistry and Western blot. Normal and mdx mice were distributed into three groups: untreated, RLX pretreated, and vehicle pretreated. Ileal preparations from the untreated animals showed spontaneous muscular contractions whose amplitude was significantly higher in mdx than in normal mice. Addition of RLX, alone or together with l-arginine, to the bath medium depressed the amplitude of the contractions in the mdx mice, thus reestablishing a motility pattern typical of the normal mice. The NOS inhibitor N(G)-nitro-L-arginine (L-NNA) or the guanylate cyclase inhibitor ODQ reversed the effects of RLX. In RLX-pretreated mdx mice, the amplitude of spontaneous motility was reduced, thus resembling that of the normal mice, and NOS II expression in the muscle coat was increased in respect to the vehicle-pretreated mdx animals. These results indicate that RLX can reverse the altered ileal motility of mdx mice to a normal pattern, likely by upregulating NOS II expression and NO biosynthesis in the ileal smooth muscle.
一氧化氮（NO）生成/释放的改变与营养不良（mdx）小鼠出现的胃肠运动障碍有关。由于激素松弛素（RLX）可上调NO生物合成，因此研究了其对营养不良（mdx）小鼠回肠自发运动及一氧化氮合酶（NOS）表达的影响。通过力-位移传感器在体外记录回肠标本的力学反应。采用免疫组织化学和蛋白质印迹法评估NOS同工型的表达。将正常和mdx小鼠分为三组：未处理组、RLX预处理组和溶剂预处理组。未处理动物的回肠标本显示出自发性肌肉收缩，mdx小鼠的收缩幅度显著高于正常小鼠。向浴液中单独或与L-精氨酸一起添加RLX可降低mdx小鼠的收缩幅度，从而恢复正常小鼠典型的运动模式。NOS抑制剂N（G）-硝基-L-精氨酸（L-NNA）或鸟苷酸环化酶抑制剂ODQ可逆转RLX的作用。在RLX预处理的mdx小鼠中，自发运动的幅度降低，类似于正常小鼠，并且与溶剂预处理的mdx动物相比，肌层中NOS II的表达增加。这些结果表明，RLX可能通过上调回肠平滑肌中NOS II的表达和NO生物合成，将mdx小鼠回肠运动的改变恢复为正常模式。
