Effects Of Shenfu Injection On Blood Glucose In Rabbits Undergoing Cardiopulmonary Bypass And Its Mechanism

Objective To observe the effects of shenfu injection (SFI) on blood glucose, insulin(INS), the expressions of insulin signal transduction molecules and oxidative stress indicators in rabbits undergoing cardiopulmonary bypass (CPB). To investigate the mechanism of SFI regulating blood glucose in rabbits undergoing CPB.Methods Thirty New Zealand white rabbits weighing 2.4±0.2 kg, were divided into three groups (n=10) at random irrespective of gender: sham operation group (group Sham), CPB group (group CPB), SFI pretreatment group (group SCPB). The animals of group SCPB were administered SFI 10 ml/kg by intraperitoneal injection at the second day and the first day before CPB and 30 min before induction of anesthesia, and the animals of group Sham and group CPB were administered NS 10 ml/kg by intraperitoneal injection at the same time. The animals of group CPB and goup SCPB were established the model of CPB, and the animals of group Sham were not. The plasma concentrations of glucose and insulin were detected at 5 min after induction of anesthesia (T1), instantly after aortic cross-clamping (T2), reperfused 5 min (T3),35 min (T3) and 75 min (T5) respectively, and assessed insulin resistance (IR) level by the homeostasis model assessment insulin resistance index (IRI). Got the rabbits INS peripheral and pancreatic target tissue (right hind limb quadriceps and pancreatic tissue) when reperfused 80 min. The expressions of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3 kinase p85 (PI3K p85) and glucose transporter 4 (GLUT4) in skeletal muscle, and the expressions of insulin, IRS-1, PI3K p85 and glucose transporter 2 (GLUT2) in pancreatic islets were detceted by immunehistochemistry. The malonaldehyde (MDA) and reduced glutathione (GSH) contents in skeletal muscle and pancreas of rabbits were measured by chromatometry.Results (1) The plasma concentrations of glucose were higher at T2～5 than at T1 in each group (P<0.05). The plasma concentrations of glucose were higher at T2～5 in group CPB and group SCPB than group Sham (P<0.05). The plasma concentrations of glucose were lower at T2～5in group SCPB than group CPB (P<0.05). (2) The plasma concentrations of INS were higher at T2～5 than at T1 in each group (P<0.05). The plasma concentrations of insulin were higher at T2～5 in group CPB and group SCPB than group Sham (P<0.05). The plasma concentrations of insulin were higher at T2～5 in group SCPB than group CPB (P<0.05). The expression of insulin in islets increased in group CPB and group SCPB as compared with group Sham (P<0.05). The expression of insulin in islets increased in group SCPB as compared with group CPB (P<0.05). (3) The IRI were higher at T2～5 than at T1 in each group (P<0.05). The IRI were higher at T2～5 in group CPB and group SCPB than group Sham (P<0.05).The IRI were lower at T2～5 in group SCPB than group CPB (P<0.05). (4) There was no significance difference of the IRS-1 expression in skeletal muscle in each group (P>0.05). The expressions of PI3K p85 and GLUT4 in skeletal muscle decreased in group CPB and group SCPB as compared with group Sham (P<0.05). The expressions of PI3K p85 and GLUT4 in skeletal muscle increased in group SCPB as compared with group CPB (P<0.05). (5) The expressions of IRS-1, PI3K p85 and GLUT2 in islets increased in group CPB and group SCPB as compared with group Sham (P<0.05). The expressions of IRS-1, PI3K p85 and GLUT2 in islets increased in group SCPB as compared with group CPB (P<0.05). (6) The MDA contents was higher in skeletal muscle and pancreas of group CPB and group SCPB than group Sham (P<0.05). The MDA contents was lower in skeletal muscle and pancreas of group SCPB than group CPB (P<0.05). (7)The GSH contents was significantly lower in skeletal muscle and pancreas of group CPB and group SCPB than group Sham (P<0.05). The GSH was higher in skeletal muscle and pancreas of group SCPB than group CPB (P<0.05).Conclusion (1) CPB could lead to rabbits peripheral IR which caused hyperglycemia, rabbits islet IR wasn't observed in this study. (2) SFI could regulate blood glucose to some extent by lessening peripheral IR and increasing insulin secretion of rabbits during CPB. (3) SFI reduced oxidative stress in skeletal muscle and pancreatic islets of rabbits during CPB, which may up-regulate the expressions of peripheral and islet cells signal transduction molecules to lessen peripheral IR and increase insulin secretion.