Noda T, Iwakiri R, Fujimoto K, Yoshida T, Utsumi H, Sakata H, Hisatomi A, Aw T Y
Department of Internal Medicine, Saga Medical School, Nabeshima, Saga, Japan.
Metabolism. 2001 Mar;50(3):259-64. doi: 10.1053/meta.2001.21030.
Intestinal mucosal growth is a common, but uncharacterized, observation associated with diabetes mellitus. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. To determine the contribution of apoptosis to the overall maintenance of intestinal growth, we examined intestinal apoptosis in the well-characterized streptozotocin (STZ)-induced diabetes rat model. Rats were injected with STZ (75 mg/kg body weight), thereafter they were allowed free feeding or restricted feeding for 3 weeks. Food intake and intestinal mucosal height were evaluated. In a second experiment, additional groups of animals were injected with STZ and were fed ad libitum for 1 or 3 weeks. Ornithine decarboxylase (ODC) activity, ratio of fragmented DNA to total DNA, electrophoresis of fragmented DNA, and Western blot analysis of caspase-3 were examined. Food intake gradually increased in free-feeding rats after induction of diabetes. Intestinal mucosal height in free-feeding diabetic rats was approximately 25% longer than controls, but this increase in mucosal height was not observed in restricted-fed diabetic rats (25 g/d). ODC activity in intestinal mucosa in diabetic rats did not differ from that of control rats. Percent fragmented DNA of diabetic rats 1 week after STZ injection was significantly lower than that of control rats, and this decrease returned to the control level 3 weeks after STZ treatment. Active form of caspase-3 was attenuated 1 week after drug treatment. Attenuated effect of diabetic rats on intestinal apoptosis did not affect increased apoptosis after ischemia-reperfusion. Suppression of apoptosis in the early days of STZ-induced diabetes was responsible for the increased mucosal height in the small intestine in STZ-induced diabetic animals.
肠黏膜生长是糖尿病常见但尚未明确特征的一种表现。上皮细胞稳态通过细胞增殖和细胞死亡的调节得以平衡。为确定细胞凋亡对肠道生长整体维持的作用，我们在特征明确的链脲佐菌素（STZ）诱导的糖尿病大鼠模型中检测了肠道细胞凋亡情况。给大鼠注射STZ（75mg/kg体重），之后让它们自由进食或限制进食3周。评估食物摄入量和肠黏膜高度。在第二个实验中，给另外几组动物注射STZ并随意喂养1周或3周。检测鸟氨酸脱羧酶（ODC）活性、DNA片段与总DNA的比率、DNA片段电泳以及半胱天冬酶 - 3的蛋白质印迹分析。糖尿病诱导后，自由进食的大鼠食物摄入量逐渐增加。自由进食的糖尿病大鼠肠黏膜高度比对照组大约长25%，但在限制进食（每天25g）的糖尿病大鼠中未观察到黏膜高度的增加。糖尿病大鼠肠黏膜中的ODC活性与对照大鼠无差异。STZ注射1周后糖尿病大鼠的DNA片段百分比显著低于对照大鼠，STZ处理3周后这种降低恢复到对照水平。药物治疗1周后半胱天冬酶 - 3的活性形式减弱。糖尿病大鼠对肠道细胞凋亡的减弱作用并不影响缺血再灌注后细胞凋亡的增加。STZ诱导糖尿病早期细胞凋亡的抑制是STZ诱导糖尿病动物小肠黏膜高度增加的原因。
