Jawerbaum A, Gonzalez E T, Novaro V, Faletti A, Sinner D, Gimeno M A
Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Reprod Fertil Dev. 1998;10(2):191-6. doi: 10.1071/r97077.
Embryonic development, prostaglandin E (PGE) generation and nitric oxide synthase (NOS) activity during organogenesis were evaluated in an experimental rat model of non-insulin-dependent diabetes (NIDD) generated by neonatal administration of streptozotocin. Gross malformations were detected in 5% of NIDD embryos and these embryos were all non-viable; in the other 95%, growth was retarded but no congenital abnormalities were found. Control embryos were all alive and not malformed. The NIDD 11-day embryos secreted more PGE into the incubation medium than did controls. The NO donor SIN-1 increased PGE production in both control and NIDD embryos. A NOS inhibitor (L-NMMA) reduced PGE generation in both experimental groups, suggesting a modulatory role of NO on embryonic PGE production. Activity of NOS was higher in NIDD 11-day embryos than in controls. Treatment in vivo of control and NIDD rats (Days 7-11 of gestation) with a NOS inhibitor (L-NAME; 5 mg kg(-1) i.p.) reduced embryonic PGE production and induced a higher resorption rate and an increase in neural-tube defects. The results suggest that NO modulates PGE generation in the organogenetic embryo. In the NIDD model, overproduction of NO is observed, this NO probably enhancing embryonic PGE production. The relationship between PGE generation and the appearance of congenital abnormalities is discussed.
在通过新生期注射链脲佐菌素建立的非胰岛素依赖型糖尿病（NIDD）实验大鼠模型中，评估了器官发生过程中的胚胎发育、前列腺素E（PGE）生成及一氧化氮合酶（NOS）活性。在5%的NIDD胚胎中检测到严重畸形，这些胚胎均无法存活；在其他95%的胚胎中，生长发育迟缓，但未发现先天性异常。对照胚胎均存活且无畸形。NIDD 11日龄胚胎向孵育培养基中分泌的PGE比对照胚胎多。NO供体SIN-1可增加对照胚胎和NIDD胚胎中的PGE生成。一种NOS抑制剂（L-NMMA）可降低两个实验组中的PGE生成，提示NO对胚胎PGE生成具有调节作用。NIDD 11日龄胚胎中的NOS活性高于对照胚胎。用NOS抑制剂（L-NAME；5 mg kg(-1)腹腔注射）对对照大鼠和NIDD大鼠进行体内处理（妊娠第7 - 11天），可降低胚胎PGE生成，并导致更高的吸收率和神经管缺陷增加。结果提示NO调节器官发生期胚胎中的PGE生成。在NIDD模型中，观察到NO过量生成，这种NO可能增强胚胎PGE生成。本文讨论了PGE生成与先天性异常出现之间的关系。
