| Objectives (1)To observe the microstructural and ultrastructural changes of the neurons in hippocampus of hyperlipidemia rats. (2)To observe the expressive changes of nNOS and NT-3 immunoreactive neurons in hippocampus of hyperlipidemia rats. (3) To investigate the relationship between hyperlipidemia and some degenerative diseases in the central nervous system and explore the possible mechanism. Methods Sprague-Dawley rats were randomly divided into control group (10 rats, fed with normal diet) and experimental group (10 rats, fed with high lipid diet). After fed on for 6 weeks, rats were let blood for assaying serum lipids then killed for obtaining brains through transcardiac perfusion for fixation. Besides light microscope and transmission electron microscope (TEM) was used to observe the microstructure and ultrastructures of neurons in hippocampus, immunohistochemical SABC staining were also used. And the optic density of nNOS and NT-3 immunoreactive neurons in hippocampus was detected by computerized image pattern analysis. All experimental results were statistical analysed by the software of SPSS 10.0. Results (1) Serum TC and LDLC of experimental and control group were (6.65 + 2.61)mmol/L, (4.41 + 2.21)mmol/L and (1.58 + 0.53) mmol/L, (0.07 + 0.10)mmol/L, and the difference was significant. (P<0.01). But serum levels of TG, VLDLC and HDLC changed little. (2) Under light microscope hippocampal cortex of rats in control groups consisted of molecular layer, pyramidal layer and polymorphic layer. Most cells in pyramidal layer were regular pyramidal cells. Moreover, some small sporadic basophilic neurons were seen in this layer. Dentate gyrus also consisted of three layers, i.e. molecular layer, granular cell layer and polymorphic layer. Within which granular cell layer was composed of severalstrata of compact granular cells with small and round nuclei. Compared with control groups, the microstructures of hippocampus in experimental groups changed little. (3) Under TEM the ultrastructures of neurons in rats' hippocampus in experimental group presented a series of pathologic changes in contrast with control group, including that rough endoplasmic reticula expanded and ruptured into vesicles, ribosomal granules broke away, mitochondria swelled and ruptured, mitochondrial crista broke, Golgi complexes swelled and their polarity disappeared, the constitutions of synapses which contained small clear and large dense cored synaptic vesicles were unclear and the numbers of small clear synaptic vesicles slightly decreased, myelin sheaths swelled, broke up and its interspace enlarged, and so did the capillary endothelia. It was significant that lots of lipid droplets accumulated in neurons or appeared in axises and stroma. (4) nNOS immunoreactive neurons in both groups were located in pyramidal layer of hippocampus and in granular cell layer of dentate gyrus by immunohistochemical SABC staining. In control group the nNOS neurons were few in quantity and sporadic in distribution, whereas in experimental group nNOS neurons were more in quantity and dense in distribution especially in CA3 area. NT-3 immunoreactive neurons in both groups were distributed densely in pyramidal layer of hippocampus and in granular cell layer of dentate gyrus by immunohistochemical SABC staining. In control group NT-3 neurons were high positive in cytoplasm and nuclei negative. In experimental group NT-3 neurons are weekly positive and less in quantity especially in CA1 area. (5) Compared with control group, mean optical density level of nNOS and NT-3 immunoreactive neurons in rats hippocampus increased and decreased respectively. All the differences were significant, in which CA3 and CA1 regions were the most. Conclusions (1) The level of serum lipids revealed that the study copied the clinical pattern of type II a hyperlipidemia which is characterized with only increased LDL and TC. (2) A series of pathologic ultrastructural changes of neurons in hippocampus of rats could be induced by hyperlipidemia. (3) In hippocampus of hyperlipidemia rat th...
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