Proliferation And Apoptosis Of Different Doses Of GLP-1 On Islet β-cell Of Intrauterine Growth Retardation In Neonatal Rats

ObjectiveTo reserch the expression of insulin, Caspase-3 and PDX-1 protein of isletβ-cell of intrauterine growth retardation in neonatal rats by hypodermic injection different doses of GLP-1, and to discuss GLP-1 on isletβ-cell of intrauterine growth retardation in neonatal rats whether can promoteβ-cell proliferation or inhibit apoptosis and the relation of dose of GLP-1 on isletβ-cell of intrauterine growth retardation in neonatal rats.Methods90 health mature virgin female Wistar rats and 15male Wistar rats, weighing 220-250 grams, are cohabited in a cage by the proportion of 6:1 in evening. Vaginal secretion smear of female rats are inspected the following morning, and the sperm are observed under microscope as the first day of pregnancy. The pregnant rats are reared in the cage separately and let them natural birth. Diagnostic criteria for IUGR:the average weight of born alive in control group minus two times standard deviations (<5.17 g) as the diagnostic criteria of IUGR. Pregnant rats of IUGR group fed on 7% protein diet during pregnancy to establish the model of IUGR rats and 20% protein diet during lactation. The control group fed on 20% protein diet during the whole pregnancy and lactation. IUGR rats were randomly divided into four groups:①20ug/kg GLP-1 hypodermic injection group (IUGR 20 group);②60ug/kg GLP-1 hypodermic injection group (IUGR 60 group);③100ug/kg GLP-1 hypodermic injection group (IUGR 100 group);④IUGR control group without any intervention (IUGR group). Each group contains 16 IUGR rats. Animals were killed 7 days or 21 days after birth. The proliferation and apoptosis of isletβ-cell are detected by Immunocytochemistry and observe islet morphology and the expression of insulin protein and Caspase-3 protein in neonatal rat of 7 days or 21 days after birth, and calculate the beta cell mass(BCM), and the expression of PDX-1 protein are detected by western blot.Results1.Fasting glucose and plasma insulin:7 days and 21 days after birth, C group, IUGR group, IUGR 20 group, IUGR 60 group and IUGR 100 group were not significantly change than 1 day after birth (P>0.05).2.Insulin protein expression:(1) 7 days after birth, insulin protein expression of isletβ-cell of C group rats was significantly higher than IUGR group, IUGR 20 group, IUGR 60 group and IUGR 100 group (p<0.05); there was no significant difference among IUGR group, IUGR 20 group, IUGR 60 and IUGR 100 group (P>0.05). (2) 21 days after birth, P-cell insulin protein expression of IUGR 100 group rats was significantly higher than IUGR group,but still significantly lower than C group (p<0.05); there was no significant difference among IUGR group, IUGR 20 group and IUGR 60 group (P>0.05).3.Caspase-3 protein expression:7 days after birth, Caspase-3 protein expression of isletβ-cell of C group rats was significantly lower than IUGR group, IUGR 20 group, IUGR 60 group and IUGR 100 group (p<0.05); there was no significant difference among IUGR group, IUGR 20 group, IUGR 60 and IUGR 100 group (P>0.05).21 days after birth, Caspase-3 protein expression of IUGR 100 group rats was significantly lower than IUGR group, but still significantly higher than C group which was a significant difference (p<0.05); there was no significant difference among IUGR group, IUGR 20 group and IUGR 60 group (P>0.05).4.PDX-1 protein expression:21 days after birth, PDX-1 protein expression of IUGR 100 group rats was significantly higher than IUGR group (p<0.05),but still significantly lower than C group (P>0.05); there was no significant difference among IUGR group, IUGR 20 group and IUGR 60 group (P>0.05).ConclusionsNeonatal rats are hypodermic injected enough dose of GLP-1 early after birth, lasting for a long time, can promote the proliferation of isletβ-cell of IUGR rats and inhibit their apoptosis, and can protect isletβcell function of IUGR rats.