Font Size: a A A

The Expression Of Angiotensin Ⅱ Type2 Receptor In Acute Renal Ischemia And Reperfusion And The Effect On Inducing Renal Tubular Cells Apoptosis

Posted on:2005-12-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:D LiFull Text:PDF
GTID:1104360122990957Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
IntroductionAcute renal injury is the main recourses of neonate death and injury, usually results from asphyxia, cold injury, shock, hemolysis and hemorrhage, and the serious may lead to acute renal failure, subsequently comes to multiorgan functional failure, the neonate dies. Among them perineonate asphyxia is the main dangerous factor.The chief pathophysiological character of perineonatal asphyxia is that a serious of metabolism disorders and organs injuries. The kidney is the chief injured organ for its high history metabolism rate. Perinatal asphyxia occurs in intrauterine mostly , and 80-90% in perinatal period. We' ve achieved some advances for the successful foundation of intrauterine ischemia and ischemia/reperfusion model.Angiotensin H (Ang II ) is a most active peptide in kidney, a potent inter-renal vasoconstrictor and also modulates glomerular filtration rate by exerting direct effects on afferent and efferent arteriolar tone and also the growth of tubu-lars. Many results have shown that Ang II acts on the conscious renal injury directly , not only increasing the pressure of glomerular through the effect on total or local homodynamic.To date, two subtypes of Ang II receptor have been identified, AT1 receptor and AT2 receptor. Most of the known functions of Ang II appear to be mediated via AT1 receptor subtype, while the function of AT2receptors are poorly understood. AT2 receptor is present in abundance in fetal kidney; disappear shortly after birth, the potent role on fetal development. Studies have shown that in the pathological condition, the AT2 receptors which not express or express less mayre -express or express more, indicate that AT2receptors take part in the course of some diseases.The pathology of ischemia and ischemia/reperfusion renal injury is that the vasoconstriction, as well as endothelial injury, then the inflammatory response by cells adhesion, finally cells death ( necrosis or apoptosis). As a high expressed receptor in pregency, whether AT2 receptor is changed in the perinatal ischemia and ischemia/reperfusion renal injury or not, no report has been found. It has shown that apoptosis plays a critical role in hypoxia/reperfusion injury. Earlier studies have focused on the chronic hypoxia or other chronic injuries. The potent role of apoptosis in acute ischemia/reperfusion injury has been scarcely reported. In order to discuss the role of AT2 receptor, in vivo we made a perinatal acute ischemia and ischemia/reperfusion model of rat, analyzed the AT2 receptor expression by immunohistochemistry technique and RT - PCR, by TUNEL we studied the apoptotic cells in kidney after acute injury, and the Caspase - 3 expression by immunohistochemistry.The relationship between AT2 receptors expression and apoptosis during the acute ischemia and ischemia/reperfusion injury, whether the renal cells especially the renal tubular cells which are most sensitive to injury are induced by AT2 receptor activity . In vitro we used renal tubular cells of rats, after primary culture, subculture cells ere obtained, cells were diffused with Ang II and CGP -42112A( potent selective AT2 receptor agonist) , discussed the effects on the apoptosis of renal tubular cells of different drug and different doses at different times, analyzed by flow cytometry and RT - PCR. The aim is to find the role of AT2 receptor on renal tubular cells apoptosis induced by Ang II Materials and methods一 In vivo .1. Animal model.The pregnant 21 days Wistar rats were anesthetized intraabdominally, two - born uterus and vessels supplying uterus and ovary were exposed, arterial clamp occluded one side of vessels. The other side was regarded as sham opera-tion group. The ischemia time was 5min, 15min, and 30min respectively, then the clamp was taken off for reperfusion. The measured time after reperfusion was 0min, 30min, 2h, 6h, and 24h respectively.2. Sample collecting and dealing.Reaching measured time, uterus born was opened immediately and pups were removed. The pups were sacrificed by c...
Keywords/Search Tags:Ischemia/reperfusion, fetal, rat, Angiotensin II, AT2 receptor, apoptosis, Caspase-3, TUNEL, cell culture, CGP-42112A
PDF Full Text Request
Related items