9-顺维A酸诱导肺癌细胞L78凋亡及其与Rb和Cyclin D1基因表达的关系

目的研究9-顺维A酸(9-cis-retinoic acid, 9-cis RA)诱导肺鳞癌细胞株L78凋亡作用及其与Rb、Cyclin D1基因表达的关系,初步探讨其作用机制. 方法体外培养肺鳞癌细胞株L78,随机分为两组,实验组加入浓度为5 μmol/L的9-cis RA;对照组加入浓度为0.1%二甲亚砜.两组均培养48小时后用免疫组织化学法检测L78细胞中Rb基因表达率,用流式细胞仪技术分别检测Rb、Cyclin D1基因表达率和肿瘤细胞凋亡率, 并研究三者之间的相关关系. 结果实验组肺鳞癌细胞株L78细胞Rb基因表达明显增强,Cyclin D1基因表达降低,细胞凋亡率增高(P＜0.01).Rb基因表达率与细胞凋亡发生率呈正相关(r=0.854,P＜0.05),Cyclin D1基因表达率与细胞凋亡发生率呈负相关(r=-0.812,P＜0.05). 结论 9-cis RA可能通过Rb基因表达增强和Cyclin D1基因表达降低途径,使细胞明显阻滞在G0/G1期,并诱导肺鳞癌细胞株L78细胞凋亡.     

人参皂甙单体Rb1对多药耐药细胞系 K562/HHT的耐药逆转作用

目的：探讨中药钙离子通道拮抗剂人参皂甙单体Ｒｂ１,对白血病多药耐药细胞系（Ｋ－５６２／ＨＨＴ）的耐药逆转作用。方法：药物敏感试验采用四唑氮盐（ＭＴＴ）比色试验法。结果：Ｒｂ１在０～８０ μｍ ｏｌ／Ｌ浓度范围内对Ｋ５６２／ＨＨＴ未见明显毒性作用;２０ μｍ ｏｌ／Ｌ、４０ μｍ ｏｌ／ＬＲｂ１ 耐药逆转倍数分别为４．４、７．９ 倍。结论：Ｒｂ１ 可以逆转Ｋ５６２／ＨＨＴ的多药耐药性,并呈剂量依赖性     

Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis

Regulation of the cell cycle is intimately linked to erythroid differentiation, yet how these processes are coupled is not well understood. To gain insight into this coordinate regulation, we examined the role that the retinoblastoma protein (Rb), a central regulator of the cell cycle, plays in erythropoiesis. We found that Rb serves a cell-intrinsic role and its absence causes ineffective erythropoiesis, with a differentiation block at the transition from early to late erythroblasts. Unexpectedly, in addition to a failure to properly exit the cell cycle, mitochondrial biogenesis fails to be up-regulated concomitantly, contributing to this differentiation block. The link between erythropoiesis and mitochondrial function was validated by inhibition of mitochondrial biogenesis. Erythropoiesis in the absence of Rb resembles the human myelodysplastic syndromes, where defects in cell cycle regulation and mitochondrial function frequently occur. Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation.     

Effects of selective α1 and α2 adrenoceptor active drugs on 86Rb+ efflux from pieces of rat parotid gland

Minute pieces of rat parotid gland were used in studies of adrenergic regulation of K+ efflux using ⁸⁶Rb+ as a probe for K+. Noradrenaline induced a concentration-dependent Rb+ efflux, whereas the β₁-selective agonist prenalterol was without effect. On the other hand, the β₂-selective drug, terbutaline, at high concentrations displayed a small enhancement of Rb+ -secretion. The selective α₁-adrenoceptor drug, phenylephrine, was as potent as noradrenaline, whereas the α₂-agonist clonidine had only a small effect. The noradrenaline-induced Rb+-efflux was effectively inhibited in the presence of prazosin, an α₁-blocker, whereas the α₂-antagonist, yohimbine, was roughly 50 times less potent. The results suggest that catecholamine-induced K+-secretion from the rat parotid gland is mediated via activation of post-synaptic α-adrenoceptors of the α₁-subtype.     

人参花总皂甙在体外对小鼠NK活性的影响

人参是著名的补益类中草药,具有广泛的药理作用。而人参皂甙是人参的主要药用有效物质。国内已有人从免疫学的角度研究人参花总皂甙,但尚未见到人参花总皂甙影响NK活性的报导。本实验首先就~(125)IUdR释放法的方法学作了一些探讨,然后观察了人参花总皂甙在体外对小鼠脾细胞NK活性的影响。材料与方法一、材料: (1)人参皂甙(ginsenoside缩写GS):本校化学教研室制备、鉴定后供给。(2)YAC—1细胞:医科院基础研究所免疫室惠赠。(3)IMDM培养基:美国Grand Island Biological Company生产。(4)~(125)IUdR(~(125)I脱氧尿嘧啶核苷):     

Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex,hippocampus, and lateral ventricle after subcutaneous administration

The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified.     

HPLC法测定骨刺宁片中人参皂苷Rg1、人参皂苷Re含量

目的采用HPLC法测定骨刺宁片中人参皂苷Rg1、人参皂苷Re含量。方法 Kromasil C18色谱柱(250 mm×4.6 mm,5μm);乙腈-0.05 mol.L-1磷酸溶液(20∶80)为流动相,流速为1.0 ml.min-1;检测波长为203 nm。结果人参皂苷Rg1线性范围为0.127～1.524 g.L-1(r=0.999 8,n=6),平均回收率为97.8%,RSD为0.75%(n=6),人参皂苷Re线性范围为0.023～0.276g.L-1(r=0.999 7,n=6),平均回收率为99.9%,RSD为0.46%(n=6)。结论该方法准确、简便,可用于该品的质量控制。