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1986年以来,本实验室发现丙谷胺能促进动物和人的胆汁分泌,后来又发现丙谷胺可降低实验动物的胆石生成率。为探讨丙谷胺这一新药理作用的机制,进行了肝细胞和细胞膜水平的研究。结果表明,丙谷胺能降低离体大鼠肝细胞对~(14)C-甘氨胆酸的净摄取,并显著增高大鼠肝细胞膜Na~+、K~+-ATP酶活性,提示丙谷胺可能是通过激活肝细胞膜Na~+、K~+-ATP酶活性和增加水和电解质排量而利胆,而并不是通过增加肝细胞对胆酸的摄取而利胆。丙谷胺还能对抗生长抑素对肝细胞膜Na~+、K~+-ATP酶活性的抑制作用。这一结果为阐明丙谷胺抑制实验性胆石生成的作用机制提供了依据。
Since 1986, our laboratory found that proglumide promoted bile secretion in both animals and humans, and later proglumide was found to reduce gallstone formation in experimental animals. In order to explore the mechanism of promethazine, a new pharmacological action, the level of hepatocyte and cell membrane was studied. The results showed that promethazine could reduce the net uptake of ~ (14) C-glycocholic acid in isolated rat hepatocytes and significantly increase the Na ~ +, K ~ + -ATPase activity in rat hepatocytes, suggesting that C Glutamine may be beneficial to gallbladder by activating the activity of Na ~ +, K ~ + -ATPase in liver cell membrane and increasing the displacement of water and electrolyte, but not by increasing hepatocyte uptake of cholic acid. Prothymine can also counteract the inhibitory effect of somatostatin on the activity of Na ~ + and K ~ + -ATP in liver cell membrane. This result provides a basis for elucidating the mechanism by which proglumide inhibits experimental gallstone formation.