Roles Of Adenosine A_2A Receptor On The Inhibitory Effects Of Prenatal Alcohol Exposure To RRDA Of Neonatal Rat

Background Alcoholism is one of the factors that affect human’s health. It not only damage to personal physical and mental health, but also has a negative effect to society. Women drinking during pregnancy can severely affect fetal growth and development, such as fetal alcohol syndrome (fetal alcohol syndrome, FAS), and central nervous system disorders is one of its characteristics. The stable basic rhythmic respiration originate in the medullary respiratory center, and the stability of rhythmic respiration is very important for maintaining many of the body’s functions. Central respiratory system diseases, especially the lesion of medullary respiratory center, are common diseases and frequently encountered disease in the clinical work, and there are more and more abnormal central respiratory induced by alcoholism, therefore, it has a far-reaching significance to study the influence of prenatal alcohol exposure on the function of medullary respiratory center.Objective To explore the mechanism of prenatal alcohol exposure depression the function of medullary respiratory center of neonatal rat via down-regulating of adenosine A2A receptor by observing the change of rhythmic respiratory discharge activities(RRDA) and adenosine A2A receptor protein and mRNA expression in neonatal rat medullary slice induced by prenatal alcohol exposure.MethodsHealthy Sprague-Dawley rats were randomly divided into control and prenatal alcohol exposure groups. Adult rats in control group and experimental group were same breeding except the rats in prenatal alcohol exposure group had access to8%(v/v) alcohol solution as sole drinking water for1month before mating and throughout the pregnancy and lactation. 1.Sprague-Dawley rat (0-3days) medullary slices was made, and recorded the RRDA in the medullary slice.Observe the roles of adenosine A2A receptor agonist2-[4-[(2carboxyethyl)phenyl]ethylamino]-5-Nethylcarboxamidoadenosine(CGS21680)and antagonist5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine (SCH58261) on RRDA in the medullary slice of control group and prenatal alcohol exposure group rats, to clear whether adenosine A2A receptor take part in the inhibitory effects of prenatal alcohol exposure to medullary respiratory center of neonatal rat.2. Using Western Blot technology to research adenosine A2A receptor protein level in prenatal alcohol exposure neonatal rats slices.3. Using qRT-PCR technology to research adenosine A2A receptor mRNA level in prenatal alcohol exposure neonatal rat slices.Results1. Control group and prenatal alcohol exposure group slices discharge were stability without attenuation in60min, and the experiment model were stable and reliable. Prenatal alcohol exposure group slices discharge was weaker than control group. Adenosine A2A receptor agonist CGS21680could excite slices discharge of the two groups, and control group excited effect was stronger than prenatal alcohol exposure group. Adenosine A2A receptor antagonist SCH58261had inhibitory effect on slices discharge of the two groups, while control group inhibitory effect was stronger than prenatal alcohol exposure group.2. Western Blot results show that, prenatal alcohol exposure down regulated adenosine A2A receptor protein level in prenatal alcohol exposure neonatal rats slices.3. qRT-PCR results show that, prenatal alcohol exposure down regulated adenosine A2A receptor mRNA level in prenatal alcohol exposure neonatal rats slices.Conclusions1. Prenatal alcohol exposure depresses RRDA of the medullary slice, inhibits the respiratory function of medulla. 2. Inhibit RRDA by down-regulating the adenosine A2A receptor and mRNA level perhaps is one of the mechanisms of prenatal alcohol exposure depresses respiratory function of medulla of neonatal rats.