The aim is to optimize the anti-inflammatory effect and the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bi...The aim is to optimize the anti-inflammatory effect and the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods in 30 Wistar rats. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different dose. The concentrations of aquaporins 4 (AQP4), matrix metalloproteinases9 (MMP9) and cyclooxygenase 2 (COX2) in serum and brain tissue were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The best therapeutic time window and dose of picroside II in cerebral ischemic injury were 1) ischemia 2.0 h with 20 mg/kg and 1.5 h with 20 mg/kg body weight according to the concentration of AQP4 in serum and brain tissue;2) ischemia 1.5 h with 20 mg/kg and ischemia 2.0 h with 20 mg/kg according to the concentrations of MMP9 in serum and brain tissue;and 3) ischemia 1.5 h with 10 mg/kg and ischemia 1.5 h with 20 mg/kg according to the concentrations of COX2 in serum and brain tissue respectively. According to the principle of the lowest therapeutic dose with the longest time window, the optimized therapeutic dose and time window were injecting picroside II intraperitoneally with 10 - 20 mg/kg body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury.展开更多
Diabetes mellitus is the leading cause of diabetic nephropathy;the early phase of diabetes is associated with kidney growth and hyperfiltration;several factors modulate these changes, among them, prostaglandins and an...Diabetes mellitus is the leading cause of diabetic nephropathy;the early phase of diabetes is associated with kidney growth and hyperfiltration;several factors modulate these changes, among them, prostaglandins and angiotensin II. Previous studies have shown that cyclooxygenase-2 is implicated in experimental models of diabetes. The aim of this work was to study the effect of celecoxib treatment on renal hypertrophy development in early diabetes mellitus. In our rats with early streptozotocin-induced diabetes there was renal hypertrophy, and increased renal expression of cyclooxygenase-2, AT1 receptor, and transforming growth factor-β1. Treatment with the selective cyclooxygenase-2 inhibitor celecoxib reduced the urinary excretion of prostaglandins such as prostaglandin E2, 6-keto prostaglandin F1α, and thromboxane B2. Kidney hypertrophy was reversed by the treatment, and the renal expression of cyclooxygenase-2, AT1 receptor, and transforming growth factor-β1 decreased. The renoprotective effects of celecoxib were independent of the changes in plasma glucose levels. These results confirm that cyclooxygenase-2 inhibition in rats with streptozotocin-induced diabetes decrease renal hypertrophy;this effect in turn, may be mediated by reduction of the expression of AT1 receptors and transforming growth factor-b1 in the kidney.展开更多
文摘The aim is to optimize the anti-inflammatory effect and the therapeutic dose and time window of picrosede II by orthogonal test in cerebral ischemic injury in rats. The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) methods in 30 Wistar rats. The successful models were randomly divided into sixteen groups according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different dose. The concentrations of aquaporins 4 (AQP4), matrix metalloproteinases9 (MMP9) and cyclooxygenase 2 (COX2) in serum and brain tissue were determined by enzyme linked immunosorbent assay to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The best therapeutic time window and dose of picroside II in cerebral ischemic injury were 1) ischemia 2.0 h with 20 mg/kg and 1.5 h with 20 mg/kg body weight according to the concentration of AQP4 in serum and brain tissue;2) ischemia 1.5 h with 20 mg/kg and ischemia 2.0 h with 20 mg/kg according to the concentrations of MMP9 in serum and brain tissue;and 3) ischemia 1.5 h with 10 mg/kg and ischemia 1.5 h with 20 mg/kg according to the concentrations of COX2 in serum and brain tissue respectively. According to the principle of the lowest therapeutic dose with the longest time window, the optimized therapeutic dose and time window were injecting picroside II intraperitoneally with 10 - 20 mg/kg body weight at ischemia 1.5 - 2.0 h in cerebral ischemic injury.
文摘Diabetes mellitus is the leading cause of diabetic nephropathy;the early phase of diabetes is associated with kidney growth and hyperfiltration;several factors modulate these changes, among them, prostaglandins and angiotensin II. Previous studies have shown that cyclooxygenase-2 is implicated in experimental models of diabetes. The aim of this work was to study the effect of celecoxib treatment on renal hypertrophy development in early diabetes mellitus. In our rats with early streptozotocin-induced diabetes there was renal hypertrophy, and increased renal expression of cyclooxygenase-2, AT1 receptor, and transforming growth factor-β1. Treatment with the selective cyclooxygenase-2 inhibitor celecoxib reduced the urinary excretion of prostaglandins such as prostaglandin E2, 6-keto prostaglandin F1α, and thromboxane B2. Kidney hypertrophy was reversed by the treatment, and the renal expression of cyclooxygenase-2, AT1 receptor, and transforming growth factor-β1 decreased. The renoprotective effects of celecoxib were independent of the changes in plasma glucose levels. These results confirm that cyclooxygenase-2 inhibition in rats with streptozotocin-induced diabetes decrease renal hypertrophy;this effect in turn, may be mediated by reduction of the expression of AT1 receptors and transforming growth factor-b1 in the kidney.
