肝脏X受体通过抑制中脑炎症保护小鼠黑质多巴胺能神经元的实验研究-生理学专业论文.docxVIP

第三军医大学硕士学位论文 第三军医大学硕士学位论文 PAGE PAGE 3 the protection of DA neurons in the SN is through inhibiting inflammatory reaction. In this study, the expression patterns of LXRα and LXRβ were detected in the SN of midbrain, providing morphological evidence for exploring role of LXRs in the modulating of functions of DA neurons and glia. Morphology of microglia, astrocyte, cellular body and fibers of DA neurons were compared in mice lacking one or both LXR isoforms including LXRα, LXRβ, and LXRα-/-β-/- deficient mice for exploring the effect of LXR isoforms in the microglia and astrocyte activation in the SN and its possible relation to dopaminergic neuronal survival. Then, we prepared midbrain infection model by periphery intraperitoneal injection LPS to the 4 month old female WT mice. Afterwards, we identified the protection fuction of LXR agonist and possible mechanism from external inflammation by LPS-stimulated. The main results were as follows: Both LXRα and LXRβ mRNA are expressed in the midbrain of four-month old mice, LXRβ mRNA being present at higher levels than LXRα mRNA. Immunohistochemistry confirmed that both LXR isoforms appeared in the SN neurons and small cells as glia. Compared with age-matched WT mice, microglia and astrocytes in 4-month old female LXRα-/- mice are not activated and no morphological changes were observed. However, microglia and astrocyte were over-activated in LXRβ-/- and LXRα-/-β-/- mice, of which glia over-activation are more remarkable in the LXRα-/-β-/- mice. It indicates that LXRβ plays a key role in protection of DA neurons by inhibting midbrain neuroinflammation reaction, which can be enhanced by activation of LXRα . Compared with age-matched WT mice, there is no significant difference in the number of TH-positive neurons and TH-immunoreactive(ir) fiber density in the SNpr of LXRα-/- mice.The number of TH-positive neuron in the SNC and THir fiber density in SNR were decreased in the LXRβ-/-, and extremely reduced in the LXRα-/-β-/