| Objective: The objective of this study was to build the best model of diabetes,and investigate whether metformin can be conducive to the STZ-induced diabetic rats related cognitive dysfunction.Methods: The rats was randomly assigned to two groups: 10 of them was used as the control group, 30 rats in the experimental group. ALL the rats were given a serial number after weighing and every five rats kept in one cage. The experimental group, feeding four weeks of high fat and high sugar diet, then 10 h of fasting, was treated with low-dose STZ(25 mg/kg) by intraperitoneal injection. An equal volume of normal group administered citrate buffer. Fasting glucose was detected 3 days after the injection(the content of blood sugar ≥ 11.1 mmol/L made successful model description) The success of the model were randomly divided into 2 groups : the model group and the metformin protection group. They were beginning the Morris water maze test in the first 20 weeks, together with the normal group. Ability activity of the rats was measured with learning and memory levels. At the end of the behavioral observation in the first 24 weeks, the hippocampu of sacrificed rats were collected in each group for HE staining and PCR.Results: Compared with normal group, the experimental group was significantly higher in the content of blood sugar, decreased body weight of rats. It is previously determined that the model of diabetes established by low-dose streptozotocin with induction forage, which have interaction with maintaining forage is simple and stable.Metformin obviously improved the Learning and memory ability of streptozotocin-induced diabetic SD rats models.The speed in the DM group was significantly slowly than the normal group and the Met group(P<0.05), but the Met group and the normal group had no significant difference. The total distance in the normal group was significantly shorter than the DM group(P<0.05), the met group and the normal group had no obviously difference. The time needed in the Met group to find the target platform was less than the time it takes in the DM group(P<0.05).The number of times across the target area in the Met group were distinctly increased than it in the DM group, in space exploration(P<0.05). The rats in each group within90 seconds time spending in the target quadrant were not different, but there are evident differences(P<0.05)in the Met group and the DM group. Normal hippocampal CA1 neurons cells are neat, tight, rich layers, completely with normal morphology larger nuclear in the center, large, round, clear nucleolus and nuclear membrane, cytoplasm with uniform light color; hippocampal neurons in the DM models are arranged in disorder morphological abnormalities, having smaller and longer size, staining dark, Increased cytoplasmic condensation and cell body shrinkage, very irregular polygonal shape and the structure is unclear. Hippocampus cells in the treatment group were arranged in order compared with the DM group, the loss of neuronal and the degeneration of hippocampal cells were shown to reduce relatively.Conclusion:1. Met can reduce hippocampal damage, induced by high glucose and fat combined with STZ in diabetic rats, and improve its cognitive dysfunction.2. The expression of PICK1 m RNA was decreased in hippocampus and cortex of diabetic rats induced by high glucose and fat combined with STZ.Objective: By manufacturing a model of the lateral ventricle injection of STZ,our study was to investigate whether metformin can be conducive to the STZ-induced diabetic rats related cognitive dysfunction.Methods: Screening of 30 SD rats with equal memory capacity, they were randomly divided into three groups. All rats were abdominal anaesthesia with10%chloral hydrate. Referencing to the rats stereotaxic atlas, we were going to find the target location of drilling skull in the midline incision in the rat’s head. The 10 u L STZ solution was slowly injected to the ventricle, then the needle was retained for 1 min.The same measurement and method were used to process the other side(the model group and the metformin group were injected with STZ solution, the control group was injected with saline). After the needle back, we filled target position with the self-curing dental powder, and topical used right amount of drugs to prevent infection.After 2 days to cut the wound closure, finding the original injection point position, we repeated injection adminstration.Results: Navigation test: The time taking for the target platform in the STZ+Met group was significantly reduced, compared with the STZ group.(P<0.05).Space exploration test: The time each group rats spending in the target quadrant within 90 seconds, had no difference in the Con group and STZ+Met group, but there were dominant differences between the STZ group and the other two groups(P<0.05). The number of crossing the target quadrant in the STZ+Met group was much more than it in the STZ group(P<0.05). Animal movement speed of each group had no obviously difference. Normal hippocampal CA1 neurons were normal intact larger, nuclear center, large round nucleolus nuclear membrane clear, neat, tight, rich layers, light color and uniform cytoplasm.After treating with nntracerebroventricular injection of STZ group, the structures came to be relatively abnormal morphology and disorder abnormal state.The volume of the cell became smaller and elongated, stained darkly with the nuclear pyknosis.Cell with volumetric shrinkage, had mostly very irregular shape or polygonal shape,and the hierarchy is not clear. The cells in the hippocampustissue treated by metformin arranged in order, the hippocampal neuronal loss and degeneration of the cells were also reduced. It is suggested that metformin can change neuronal injury, and have a protective effect to hippocampal neurons.The expression of PICK1 m RNA in the hippocampus of the STZ group was relatively decreased than the normal and STZ+Met group(P<0.05). The expression of PICK1 m RNA in the cortical tissue of the STZ group was also relatively decreased than the normal and STZ+Met group(P<0.05).Conclusion:1. The lateral ventricle injection of STZ-induced damage to the hippocampus of rats,Met improved lateral ventricle injection of STZ-induced cognitive dysfunction like Alzheimer ’s disease.2. Met could increase the expression of PICK1 m RNA in the hippocampus and cortical tissue of STZ intracerebroventricular injection model.It may be one of the mechanisms to reduce the cognitive dysfunction. |
PDF Full Text Request