A study on the protective role of doxycycline upon dopaminergic neuron of LPS-PD rat model rat

摘要

OBJECTIVE: To investigate the protective role of doxycycline upon the dopaminergic neuron of the lipopolysaccharide-Parkinson disease (LPS-PD) model rat and its mechanism. MATERIALS AND METHODS: Animals were randomly divided into three groups: normal control group, LPS group and doxycycline intervention. Group; establishing The PD model was created by injecting LPS stereo-tactically into the substantia nigra; observing the changes in the dopaminergic neurons and the major histocompatibility complex II (MHC II) positive microglia before and after the intervention of doxycycline with immunohistochemical staining. Using the HPLC-ED (high performance liquid chromatography-electrochemical detector) to test the changes in the striatal dopamine (DA), and DOPAC (dihydroxy phenyl acetic acid) content; adopting Western blotting was adopted to test the expression of the substantia nigra microglia MHC II (major histocompatibility complex II) protein. RESULTS: After the intervention of doxycycline, in the LPS group, the surviving dopamine neurons in the substantia nigra rose from 38% ± 5% to 79% ± 4% (p < 0.01); striatal DA and DOPAC content of the LPS group increased from 4.89 ± 0.27 and 0.70 ± 0.07 to 7.00 ± 0.34 and 1.10 ± o. 10 respectively (p < 0.01). The average number of rotation induced intraperitoneal injection of apomorphine of the animals in the LPS group reduced from (208 ± 14); time/30 min to (80 ± 12) times/30 min (p < 0.01); while the number of the MHC II positive cells in the substantia nigra pars compacta in the LPS group reduced from 835 ± 82 to 354 ± 59 (p < 0.01); Western blotting of the MHC II protein expression showed a significant reduction. CONCLUSIONS: Doxycycline can inhibit degeneration of LPS-induced dopaminergic neurons. Its neuroprotective function is achieved by downregulating the microglia MHC II expression.