小毛莨碱对结核休眠菌分了生物学特性的作用

To develop the model in which H37Rv virulent dormant Mycobaterium tuberclosis(DMT), a stationary phase, induced by low oxyen tension in vitro.There was significantly variation the expression rate of 16-kilodton alpha-small heat shock protein (16-KDa-SHSP) which is the marker of DMT in intracellular survival from different oxgen tension and the cultural time..During low oxgen tension, H37Rv virulent of DMT were cultured with Ternatolide (200mg.L-1) for 6 weeks, 16-KDa-SHSP expression significanty induced by hight concentrations of 200mg.L-1(0.08±o.24,0.16±0.05)..Ternatolide (Tern.), a active component of Ranuculus Ternatus-Chinese herb were isolated from the crude extract by solvent extraction and column chromatography. Ternatolide have been shown to contribute to killed Mycobacterium tuberculosis used in clinic treatment..Granulysin(GLS.) is a anti-bacterial petides in activated human CTL and NK cells and have the capcity to kill directly Mycobacterium tuberculosis. By competivie quantitative-reverse transcriptrase PCR(QC-RT-PCR) to sdudy the effects of Ternatolide on expression of granulysin mRNA in the activated peripheral blood lymphocytes (PBLs) of the adults with drug resistance pulmonary Mycobacterum tuherculosis (DRTB). The dosage of 100mg.L-1, 200mg.L-1 of Ternatolide significantly ehanced the GLS. mRNA expression (0.567±0.063,0.021±0.007) in PBLs in vitro..52 cases with DMTB were analyzed using a KL Imaging System in before and after treatment of Ternatolide, the expression activity of Ag-NORs of PBL was significantly different between I.S% of before and after (5.91±1.38,8.38±1.49). .These data indicate that molecular mechanism of Ternatolide against DMTB might be associated with the inducting highly level on the expression of granulysin mRNA of PBL in infected DRTB and inhibiting 16-KDa-SHSP expression in DMTB..

建立一种适于筛检药物在结核休眠菌非自复制持存期不同阶段杀灭结核休眠菌能力的体外新模型。首次创立一种结核休眠菌的临床诊断新方法。观察小毛莨碱对NRP1期和NRP2期结核休眠菌a－晶状体蛋白同源体和甘氨酸脱氢酶的表达活性和核酸合成速度的作用；并用TEM分析休眠菌超微结构的改变。从分子水平阐明小毛莨碱杀灭结核休眠菌的作用机理。