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Vascular dementia (vascular demensia, VD) is a series of cerebral vascular factors leading to brain tissue damage caused by brain dysfunction syndrome in senior general, the diagnosis has the following three or more impaired mental activities such as language, memory, visuospatial skills, emotion, personality, computing power and abstract sense [1]. Common clinical vascular dementia include: Multi-infarct dementia, a large area of ??infarct dementia, subcortical arteriosclerotic encephalopathy (Binswanger disease), special parts and hemorrhagic infarct dementia caused by dementia. disease, the majority of patients not only seriously affect the physical and mental health and quality of life, but also to society and the family brought a heavy burden. In recent years, VD's disease showed a trend of younger, increasingly the majority of research and clinicians attention. Currently the pathogenesis of VD yet entirely clear, nor precise and effective control methods, so explore the pathogenesis of VD, the development of effective treatment programs, has become a hot research field of medicine. Learning and memory is the brain's higher nervous physiological activities. Learning is the experience and skill acquisition, memory is the experience and skills of the preservation and reproduction. Learning and memory are two different neural biological processes, both interrelated and closely allow organisms to adapt to the changing external environment [3]. Numerous studies show that the hippocampus and other brain structures for learning and memory formation and maintenance is important. Memory is divided into short-term memory, short-term memory, long term memory and permanent memory of four. With longer memories may be related to brain protein synthesis, whereas the permanent memory may be associated with the establishment of new synapses on [4]. Hippocampus unique organizational structure and physiological function of nerves may be involved in the synthesis of this protein and the synapse and the establishment. The body's neurotransmitters and humoral factors involved in learning and memory processes, such as the cholinergic system, excitatory amino acid glutamate and its receptor, NO and calmodulin, that have basic medical sciences and clinical sciences widely confirmed, but because of its complex mechanisms are not yet entirely clear. Racemic 3 - Regular NBP (dl-3n-butylphthalide, NBP), by the Chinese Academy of Medical Sciences, Chinese Peking Union Medical College to develop a national one class of drugs, with completely independent intellectual property rights, first from natural plant celery seed separation and purification and synthesis of racemic yellow oily liquid, with good efficacy against cerebral ischemia. Butylphthalide mechanism against cerebral ischemia is extremely complex, is a multi-gene, multi-target, multi-link participatory process. By reducing cerebral edema, improve brain energy metabolism, improve the microcirculation of ischemic brain regions, inhibition of neuronal apoptosis, anti-thrombosis, anti-platelet aggregation, inhibition of glutamate release, decreasing the intracellular calcium concentration and inhibit free radicals and increasing antioxidant enzyme activity and other mechanisms play a role in efficacy [5]. Butylphthalide current study are mostly concentrated in the field of cerebral ischemia, lack of VD relationship between its research reports. MMPs, especially MMP-2 and MMP-9 in the pathogenesis of VD has been more and more attention of researchers, has reason to believe, MMPs may be treating VD Butylphthalide one of the targets. The experimental study investigated the racemic 3 - Regular Butylphthalide the VD in rats and its possible therapeutic mechanism, and thus to provide a scientific basis for clinical treatment. Objective: To study the racemic 3 - Regular Butylphthalide of vascular dementia rats learning and memory and hippocampal MMP-2, MMP-9 expression, and to explore Butylphthalide treatment of chronic cerebral ischemia mechanism. Research Methods :12-16-week-old male Wistar rats 160, weighing about 250-300g, were randomly divided into sham operation group (n = 40), model group (n = 40), high-dose group Butylphthalide (n = 40) (dose of 6mg/kg), butylphthalide low dose group (n = 40) (dose of 2mg/kg). Produced by 2-Vo France vascular dementia model rats were isolated carotid sham control group is not only the separation of ligation, model group, high dose group and Butylphthalide low-dose group Butylphthalide permanent carotid ligation . Butylphthalide injection Butylphthalide high-dose group and low dose group was injected intraperitoneally operative on the date that the appropriate dose Butylphthalide injection, model group were injected normal saline, sham surgery group were not administered. After administration of 1d, 3d, 5d, 7d, 14d and 30d, respectively, at each time point were randomly selected rats in each group 3, the brains were removed after cardiac perfusion at the optic chiasm 1mm and 4mm coronal incision brain tissue, removal of the cerebellum and brain stem, take the middle hippocampus, after fixation, dehydration, dipping wax, paraffin-embedded sections, immunohistochemical staining of MMP-2 and MMP-9 expression changes. The rats in each group remaining after the administration of 30d OK jumping avoidance test and Morris water maze test, test for learning and memory ability, HE staining hippocampal pathology. Data are presented as mean ± standard deviation (x ± s) that the use of SPSS 11.0 statistical software for univariate analysis of variance, using LSD-t test was used for each comparison between two groups, P lt; 0.05 considered statistically significant. Results 1. Experimental animals generally occur postoperatively the rats Maofa Ling chaos, reduced activity, listlessness and Eat drink less postoperative anesthesia time and energy regeneration time, the sham control group was significantly older than the model group, Butylphthalide Butylphthalide high-dose group and low dose group, whereas high-dose group and Butylphthalide Butylphthalide low dose group was significantly older than the model group. Sham control group after one day to restore the spirit of the NBP takes about 2-3 days treatment group, the model group the longest, about 5-7 days to recover. 2 jumping avoidance test and Morris water maze test rats in each group in the first 31 days after the test jumping avoidance test and Morris water maze test as academic performance, the rats in the first 32 days after the test jumping avoidance test and Morris water maze test as memory performance. Jumping trial and error in order to escape latency times as academic performance, latency and error times as memory performance; Morris water maze test in order to avoid latency and errors as the number of grades to stay original platform quadrant time as the memory performance. 2.1 jumping test results showed that: learning ability test, compared with model group, high dose group and Butylphthalide Butylphthalide small dose group jumping escape latency was significantly shorter, respectively (85.23 ± 12.71,56.18 ± 11.36, 57.96 ± 11.48) seconds, significantly reduced the number of errors were (4.78 ± 0.79,2.08 ± 0.41,2.09 ± 0.45); in memory tests, compared with model group, high dose group and Butylphthalide small Butylphthalide dose group was significantly longer latency, respectively (72.84 ± 10.26,152.27 ± 11.70,153.19 ± 11.58) seconds, significantly reduced the number of errors were (1.86 ± 0.13,0.53 ± 0.05,0.55 ± 0.06). 2.2 Morris water maze test results show that: in the learning ability test, compared with model group, high dose group and Butylphthalide Butylphthalide small dose group jumping escape latency was significantly shorter, respectively (80.71 ± 8.27,43.25 ± 5.29,44.74 ± 5.82) s, significantly reduced the number of errors were (37.53 ± 7.69,14.76 ± 5.01,15.68 ± 5.32); in memory tests, compared with model group, high dose group and Butylphthalide butylbenzene phthalocyanine low-dose group of the original platform quadrant time was prolonged, respectively (18.67 ± 5.39,32.35 ± 4.27,31.19 ± 4.78) seconds. 3 HE staining in hippocampus of rats sham group: neuronal degeneration and necrosis and cell swelling is not obvious, large round nuclei, tightly packed cells, clear boundaries with the surrounding neurons; Model group: neuronal degeneration and necrosis and cellular edema Obviously, nuclear condensation, and the surrounding neurons edema band; Butylphthalide treatment groups: the degree of apoptosis between neuronal degeneration in the sham group and model group, a clearer structure between neurons, no significant edema , the number of damaged neurons was significantly reduced compared with the model group, high dose group Butylphthalide neuronal damage pathology Butylphthalide low-dose group compared to light. 4. MMP-2, MMP-9 immunohistochemical staining rats in each group were in the postoperative 1d, 3d, 5d, 7d, 14d and 30d with 10% chloral hydrate anesthesia, the brains were removed, 4% paraformaldehyde perfusion-fixed, paraffin-embedded, coronal slices, using SP immunohistochemical staining method to observe the MMP-2, MMP-9 expression situation. Image acquisition system with the mining maps and image analysis software for statistical analysis of the image. Compared with model group, high dose group and Butylphthalide Butylphthalide low-dose group MMP-2, MMP-9 expression at each time point was significantly reduced, p lt; 0.05, statistically significant, indicating that NBP may reduced MMP-2 and MMP-9 expression. Conclusions: 1. Butylphthalide can improve VD model rats jumping avoidance test and Morris water maze test of learning and memory. 2 chronic ischemic hippocampal neurons VD MMP-2 and MMP-9 expression was significantly increased. 3 Butylphthalide can hippocampal neurons MMP-2 and MMP-9 expression was significantly reduced. 4 Butylphthalide for MMP-2 and MMP-9 in expression may be Butylphthalide VD therapeutic effect on one of the targets.
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