胸腺五肽酶降解机制的研究

Study on the Mechanism of Enzymatic Degradation of Thymopentin

目的研究胸腺五肽在胃肠道中的酶降解机制。方法考察胸腺五肽在人工胃液、人工肠液、纯酶(氨肽酶N、羧肽酶A、胰蛋白酶和糜蛋白酶)以及离体肠环中的降解,并探讨胸腺五肽浓度、酶抑制剂及pH值对降解的影响。结果胸腺五肽在人工胃液中稳定,在人工肠液中迅速降解,具有浓度依赖性及pH依赖性,即浓度越高,pH值越低,则降解速率越低。同时酶抑制剂(乙二胺四乙酸二钠、1,10-菲啰啉)可显著地抑制其降解,但杆菌肽的抑制作用不显著。胸腺五肽在羧肽酶A、氨肽酶N及胰蛋白酶中的降解速率分别为5.11,12.82,13.43mL.min-1,但在α-糜蛋白酶中几乎不降解。此外,胸腺五肽的降解具有显著的部位特异性,在结肠部位的降解速率最低。结论胸腺五肽易被胃肠道中的酶降解破坏,口服无效。为了开发口服给药系统必须将胸腺五肽包载于适宜的载体之中。

OBJECTIVE To evaluate the enzyme degradation mechanism of thymopentin in gastrointestinal tract. METHODS A systemic research on thymopentin degradation were carried out in artificial gastric juice, artificial intestinal juice, pure enzyme （aminopeptidase N, carboxypeptidase A, trypsin, α-chymotrypsin） and everted intestinal rings. RESULTS Thymopentin was stable in artificial gastric juice, but rapidly degraded in artificial intestinal juice, which dependent on thymopentin concentration and pH value. The higher concentration and lower pH value, the lower degradation clearance. Furthermore, enzyme inhibitors such as EDTA and 1,10-phenanthroline significantly inhibited the degradation of thymopentin, but baeitraein had not significantly different effect. In the presence of pure enzyme, the degradation clearances were 5.11, 12. 81 and 13.43 mL· min^-1 for carboxypeptidase A, aminopeptidase N and trypsin, respectively. However, thymopentin was be degraded by α-chymotrypsin. Furthermore, the degradation was highly depended on the intestinal segment, with the lowest degradation clearance observed in the colon. CONCLUSION Thymopentin was apt to degradation in gastrointestine tract. For oral administration, it must be entrapped with suitable drug delivery systems.