Departments of Anatomy, Univ. of Florence, Italy.
Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E380-91. doi: 10.1152/ajpendo.00375.2010. Epub 2010 Nov 16.
Impaired gastric motility ascribable to a defective nitric oxide (NO) production has been reported in dystrophic (mdx) mice. Since relaxin upregulates NO biosynthesis, its effects on the motor responses and NO synthase (NOS) expression in the gastric fundus of mdx mice were investigated. Mechanical responses of gastric strips were recorded via force displacement transducers. Evaluation of the three NOS isoforms was performed by immunohistochemistry and Western blot. Wild-type (WT) and mdx mice were distributed into three groups: untreated, relaxin pretreated, and vehicle pretreated. In strips from both untreated and vehicle-pretreated animals, electrical field stimulation (EFS) elicited contractile responses that were greater in mdx than in WT mice. In carbachol-precontracted strips, EFS induced fast relaxant responses that had a lower amplitude in mdx than in WT mice. Only in the mdx mice did relaxin depress the amplitude of the neurally induced excitatory responses and increase that of the inhibitory ones. In the presence of L-NNA, relaxin was ineffective. In relaxin-pretreated mdx mice, the amplitude of the EFS-induced contractile responses was decreased and that of the fast relaxant ones was increased compared with untreated mdx animals. Responses to methacholine or papaverine did not differ among preparations and were not influenced by relaxin. Immunohistochemistry and Western blotting showed a significant decrease in neuronal NOS expression and content in mdx compared with WT mice, which was recovered in the relaxin-pretreated mdx mice. The results suggest that relaxin is able to counteract the altered contractile and relaxant responses in the gastric fundus of mdx mice by upregulating nNOS expression.
据报道，在营养不良型（mdx）小鼠中，由于一氧化氮（NO）产生缺陷导致胃动力受损。由于松弛素上调了 NO 的生物合成，因此研究了松弛素对 mdx 小鼠胃底的运动反应和一氧化氮合酶（NOS）表达的影响。通过力位移传感器记录胃条的机械反应。通过免疫组织化学和 Western blot 评估三种 NOS 同工型。将野生型（WT）和 mdx 小鼠分为三组：未处理、松弛素预处理和载体预处理。在未经处理和未经载体预处理的动物的条带中，电刺激（EFS）引起的收缩反应在 mdx 比在 WT 小鼠中更强。在预先用卡巴胆碱收缩的条带中，EFS 诱导快速松弛反应，在 mdx 比在 WT 小鼠中幅度较小。只有在 mdx 小鼠中，松弛素抑制了神经诱导的兴奋性反应的幅度，并增加了抑制性反应的幅度。在存在 L-NNA 的情况下，松弛素无效。在松弛素预处理的 mdx 小鼠中，与未经处理的 mdx 动物相比，EFS 诱导的收缩反应幅度降低，快速松弛反应幅度增加。对乙酰甲胆碱或罂粟碱的反应在制剂之间没有差异，并且不受松弛素影响。免疫组织化学和 Western blot 显示，与 WT 小鼠相比，mdx 中的神经元 NOS 表达和含量显著降低，而在松弛素预处理的 mdx 小鼠中得到恢复。结果表明，松弛素通过上调 nNOS 表达来对抗 mdx 小鼠胃底的改变的收缩和松弛反应。
