Izumi Masatake, Watanabe Masahito, Sawaki Kohei, Yamaguchi Hideharu, Kawaguchi Mitsuru
Department of Orthodontics, Tokyo Dental College, Chiba, Japan.
Eur J Pharmacol. 2008 Oct 31;596(1-3):1-5. doi: 10.1016/j.ejphar.2008.07.065. Epub 2008 Aug 9.
We determined mRNA levels of bone morphogenetic protein 7 (BMP7), a growth and differentiation factor belonging to the transforming growth factor-beta superfamily, in the salivary glands of mice with streptozotocin (200 mg/kg, i.p.)-induced diabetes. We also examined the effects of BMP7 on secretion of saliva and degenerative change in salivary glands in diabetic mice. In normal mice, BMP7 mRNA levels were high in the submandibular gland and low in the parotid gland, while in diabetic mice, levels were significantly decreased in the parotid gland, but not in the submandibular gland. No significant difference was observed in mRNA levels of BMP receptors between normal and diabetic mice. In diabetic mice, pilocarpine (4 mg/kg, i.p.)-stimulated salivary secretion showed a remarkable decrease in both parotid and submandibular gland, although degree of reduction was smaller in the latter. Notable degeneration with vacuolation and atrophy was also found in parotid gland, whereas degeneration of submandibular gland was slight. Administration of BMP7 (50 and 100 microg/kg, i.v.) in diabetic mice induced a significant increase in salivary secretion, with rate of recovery higher in parotid gland than in submandibular gland. In diabetic mice, BMP7 also exhibited a powerful protective effect in degenerated salivary gland, especially in parotid gland. These results suggest that BMP7 acts to prevent diabetic damage in salivary gland, and that its cytoprotective effect is closely correlated with mRNA levels in tissue.
我们测定了链脲佐菌素(200mg/kg,腹腔注射)诱导的糖尿病小鼠唾液腺中骨形态发生蛋白7(BMP7)的mRNA水平,BMP7是一种属于转化生长因子-β超家族的生长和分化因子。我们还研究了BMP7对糖尿病小鼠唾液分泌及唾液腺退行性变化的影响。在正常小鼠中,下颌下腺的BMP7 mRNA水平较高,腮腺中的水平较低,而在糖尿病小鼠中,腮腺中的水平显著降低,而下颌下腺中的水平未降低。正常小鼠和糖尿病小鼠之间BMP受体的mRNA水平未观察到显著差异。在糖尿病小鼠中,毛果芸香碱(4mg/kg,腹腔注射)刺激的唾液分泌在腮腺和下颌下腺均显著减少,尽管后者的减少程度较小。腮腺中还发现了明显的空泡化和萎缩性退变,而下颌下腺的退变较轻。给糖尿病小鼠静脉注射BMP7(50和100μg/kg)可显著增加唾液分泌,腮腺的恢复率高于下颌下腺。在糖尿病小鼠中,BMP7对退变的唾液腺也具有强大的保护作用,尤其是在腮腺中。这些结果表明,BMP7可预防唾液腺的糖尿病损伤,其细胞保护作用与组织中的mRNA水平密切相关。