ObjectiveTo evaluate the role of N-methyl-D-aspartate (NMDA) receptor in central nervous system (CNS) injury of obstructive jaundice. MethodThe related literatures about NMDA receptor and the CNS injury caused by hyperbilirubinemia were retrieved and reviewed. ResultsThe CNS injury of obstructive jaundice was related to overactivation of NMDA receptor, which finally resulted in degeneration and necrosis of nerve cells. The NMDA receptor antagonist MK-801 could relieve the CNS injury of obstructive jaundice. ConclusionsNMDA receptor plays an important role in the CNS injury caused by hyperbilirubinemia, and the blocker of NMDA receptor has protective effects in this process. However, there is no report of MK-801 in clinical application when hyperbilirubinemia happened.
ObjectiveTo investigate the effects of different levels of resveratrol on oxidative stress injury in central nervous system of rats with obstructive jaundice and its protective effect and mechanism of oxidative stress injury. MethodsThirty two female SD rats of 6 weeks old were used as experimental object. The animals were randomly divided into four groups, 8 rats in each group. Sham operation group (SO group), the common bile duct were seperated without ligation; while the models of obstructive jaundice of obstructive jaundice group (OJ group), obstructive jaundice+low dose resvera-trol (L-Res)treatment group (OJ+L-Res group), and obstructive jaundice+high dose resveratrol (H-Res) treatment group (OJ+H-Res group) were established by operation. After the operation, the rats in OJ+L-Res group and OJ+H-Res group were treated with different doses of resveratrol, the rats in SO group and OJ group were given the same dose of normal saline. On the 14th day after operation, blood were tested for total bilirubin (TBIL), direct bilirubin (DBIL), ALT, and AST. And cerebral cortex specimen were collected, then malondialdehyde (MDA), total superoxidedismutase (T-SOD) activity, and HO-1 protein expression in the rats brain of the four groups were measured. ResultsThe levels rise of TBIL and DBIL after modeling suggested that obstructive jaundice model were estabilshed successfully, but there was no significant difference among the OJ group, OJ+L-Res group, and OJ+H-Res group. In the OJ group, OJ+L-Res group, and OJ+H-Res group, the levels of ALT, AST, and MDA were increased while levels of T-SOD and HO-1 protein expression were decreased when compared with SO group(P < 0.05). Among the OJ group, OJ+L-Res group, and OJ+H-Res group, levels of ALT, AST and MDA were lower in the treatment groups than in the OJ group(P < 0.05), while levels of T-SOD and HO-1 protein expression which reflects the oxidative stress were higher in the treatment group(P < 0.05). Different doses of resveratrol had different effects on T-SOD and HO-1 protein expression with statisticl significance (P < 0.05). ConclusionsResveratrol have little effect on TBIL and DBIL of obstrctive jaundice rats, but it can protect the liver function, and it has antioxidant properties of decreasing MDA and incresing SOD and HO-1 protein expression levels in the cerebral cortex cells of obstructive jaundiced rats.
ObjectiveTo investigate the effects of MK-801 on antioxidant system activity in the central nervous system of rats with obstructive jaundice. MethodsTwenty rats were divided into four groups: sham operation group, control group, MK-801 low dose group, and MK-801 high dose group. The control group, MK-801 low dose group, and MK-801 high dose group were the obstructive jaundice model groups (OJ groups). From the first day after operation, MK-801 low dose group were processed intraperitoneal injection of MK-801 0.025 mg/(kg·d) and MK-801 high dose group were processed intraperitoneal injection of MK-801 0.25 mg/(kg·d). Meanwhile, sham operation group and control group were injected the same volume of normal saline everyday for 10 days. Three days after operation, rats' tail vein blood were collected for examining the direct bilirubin DBIL) and total bile acids (TBA) in order to determine whether the model were successfully established. And malondialdehyde (MDA), catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC) were determined on the 10th day to evaluate the oxdative status of the rats. Results①Obstructive jaundice model was established successfully.②The content of MDA in control group, MK-801 low dose group and MK-801 high dose group were significantly increased than the sham operation group, and there was statistical difference (P < 0.05). The content of MDA decreased in MK-801groups compared with the control group (P < 0.05).③Compared with the sham operation group, the activity of CAT in control group decreased significantly (P < 0.05). The activity of CAT in the MK-801 groups increased compared with the control group with significant difference (P < 0.05). There was no statistical difference on the activity of CAT between MK-801 low dose group and high dose group (P > 0.05).④Compared with sham operation group, the activity of T-SOD was decreased significantly in control group with statistical significance (P < 0.05). The activity of T-SOD were increased in the MK-801 groups compared with control group with significant difference (P < 0.05), but the activity of T-SOD was decreased significantly in the high dose group than the low dose group (P < 0.05).⑤In the Oj groups, the T-AOC were significantly increased compared with the sham operation group, and there was statistical significance (P < 0.05). The T-AOC in MK-801 groups were increased compared with the control group with statistical significance (P < 0.05), but there was no statistical difference between the MK-801 groups. Conciusions Oxidative stress exists when obstructive jaundice occurs, and obstructive jaundice can aggravate the oxidative stress damage in the rats' central nervous system and cause increasing expression of enzymes such as CAT which enhance antioxidant capacity of the whole body. MK-801 can decrease lipid peroxidation, and increase activity of CAT and SOD as well as T-AOC in CNS of jaundice rats. But High dose of MK-801 has no better effect than low dose of MK-801. On the contrary, activity of T-SOD decrease in the high dose group than in the low dose group. Further research is needed on the specific mechanism.