ABSTRACT
OBJECTIVE To evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahy?dropyridine (MPTP)/probenecid (MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms. METHODS Male C57BL/6 mice were randomly assigned to six groups. One hour prior to MPTP/p injection, Group Ⅲ-Ⅵ mice received 10 mg·kg-1, 20 mg·kg-1, or 40 mg·kg-1 Rg1 or 3 mg·kg-1 selegiline, respectively, orally from D (-3) to D49. Group Ⅰ-Ⅱ mice received solvent water. Subsequently, GroupⅡ-Ⅵ mice received by injection MPTP-HCl (25 mg·kg- 1 bw dissolved in 0.9% saline, sc) on a 40-d schedule at intervals of 4 d between consecutive doses in combination with an adjuvant drug, probenecid (250 mg·kg- 1 bw in 0.03 mL of DMSO, ip); GroupⅠ mice were injected with saline and probenecid. Behavioral performance was assessed in the open field test, pole test and rotarod test. Neurotransmitters in the striatum were detected using HPLC. Protein levels were measured by Western blot. Pathological characteristics were examined by immunohistochemistry. Ultrastructure changes were observed by electron microscopy. RESULTS Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality, behavior defects, loss of dopamine neurons and abnormal ultrastructure changes in the SNpc. Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties. Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1b (IL-1b) in the SNpc. Rg1 also alleviated the unusual MPTP induced increase in oligomeric, phosphorylated and disease-related a-synuclein in the SNpc. CONCLUSION Rg1 protects dopaminergic neurons, most likely by reducing aberrant a-synuclein-mediated neuroinflammation, and holds promise for Parkinson disease therapeutics.
ABSTRACT
Objective To study the genotypes of representative Mycobacterium tuberculosis (M.tuberculosis) strains from China with spacer oligonucleotide typing (spoligotyping),and to investigate the prevalence of different genotypes TB in China,and analyse the relationship between genotype and drug resistance.Methods 4017 clinical isolates were collected by Chinese Center for Disease Control and Prevention from 2007 to 2008 in 31 provinces in China according to sampling principle of epidemiology.Drug susceptibility testing was performed using proportion method,and spoligotyping was chosen to carry out genotyping of these M.tuberculosis.In addition,chi-square test was used to compare the differences among the detection rate of different genotypes.Results Among the 4017 M.tuberculosis isolates,2500 ( 62.2％ ) isolates belonged to Beijing genotype.The percentage of Beijing genotypes in the northern of China was higher than that in the southern of China ( 76.5％ vs.53.2％,x2 =219.69,P ＜ 0.05 ),while T1 genotypes were more common in the southern China,compared with that in northern China ( 13.3％ vs.4.3％,x2 =219.69,P ＜ 0.05 ).The differences were statistically significant.The proportions of Rifampinresistant (21.7％ vs.21.7％ ),Ofloxacin-resistant (4.9％ vs.2.4％ ) and Multidrug-resistant ( 11.3％vs.7.4％ ) isolates among Beijing genotype strains were significantly higher than those among non-Beijing strains (x2 =22.10,14.42 and 14.83,respectively,P ＜ 0.05 ).Conclusions Beijing genotype was still predominant epidemic genotypes.The percentage of Beijing genotype showed difference between distinct areas,and the percentage of Beijing genotypes in northern China was higher than that in southern China.Beijing genotype strains reveal correlation with Rifampin-resistance,Ofloxacin-resistance and Multidrug-resistance.