AQP4与PKC在大鼠CIR后脑水肿模型中的变化及作用

目的通过研究大鼠局灶性脑缺血再灌注后水通道蛋白4（AQP4）、蛋白激酶C（PKC）表达水平的变化,来探讨两者与脑水肿之间的关系。方法通过线栓法复制大鼠大脑中动脉缺血（MCAO）再灌注模型,动物随机分为正常对照组（Norm）、假手术组（Sham）、缺血再灌注组（CIR）。参照Garcia JH法进行神经功能缺损评分、用Elliot法检测脑组织含水量、免疫组化法检测AQP4及PKC的表达。结果 CIR后6h即有神经功能缺损,脑含水量在CIR12h明显升高,1~3d时达到高峰;AQP4表达在早期水平降低,从12h逐渐升高,至CIR 24h明显升高,3d达高峰;PKC在CIR后6h开始持续性升高,至第5d仍保持较高水平。结论早期的细胞源性脑水肿可能和PKC的升高有关,后期的血管源性脑水肿可能和AQP4的升高相关。     

线粒体型天门冬氨酸氨基转移酶同工酶测定及其应用价值

目的建立免疫抑制法测定各类心脏和肝脏疾病的m-AST,观察其应用价值。方法提取纯化心肌细胞质型天门冬氨酸氨基转移酶同工酶(s-AST)酶蛋白,免疫羊制备抗人s-AST抗体,应用免疫抑制原理抑制标本中的s-AST活性,测定m-AST活性。结果血清m-AST参考值4~15 u/L,急性心肌梗死60~310、陈旧心肌梗死10~20、无梗死冠心病7~15、无心衰7~18、心衰8~25、心包炎10~16、心肌炎18~30 u/L;急性肝炎56~410、慢迁肝炎12~17、慢活肝炎18~90、有腹水肝硬化18~50、无腹水肝硬化12~30、原发性肝癌11~64、继发性肝癌16~95、肝脓肿15~21 u/L。有坏死的心、肝病m-AST明显升高。非心肝性恶性肿瘤和其他疾病基本在参考值范围内。结论测定m-AST可协助判定心、肝疾病的严重性和有无坏死。     

Mechanisms of Panax ginseng in preventing rat pheochromocytoma cells from apoptosis

Aims of the study

Although ginseng root possesses dominant central therapeutic effects and has recently undergone investigations for treating different neuronal diseases, most of its mechanisms are still unknown. Therefore, the neuroprotective mechanisms of ginseng were studied.

Materials and methods

The protection afforded by different methanol extracts of Panax ginseng (PG) was tested in a serum deprivation-induced apoptotic model using neuronal-like pheochromocytoma (PC12) cells. An MTT assay, annexin V-FITC staining, and Western blots were, respectively, applied to identify the viability of cells, the apoptotic form of cell death, and the activity of antiapoptotic signaling.

Results

The known antiapoptotic PI3-K/Akt and MEK/ERK pathways in this system were ruled out due to failure of LY 294002 and PD 98059 to block the protection by PG. A protein kinase A (PKA) inhibitor was found to block the protection by PG and PG-induced CREB phosphorylation, suggesting that the PKA/CREB pathway mediates the protective effect of PG. Downregulation of classical and novel PKCs failed to block the protection by PG, while an atypical PKC inhibitor blocked protection by PG.

Conclusions

PKA and atypical PKC are important for the protection afforded by PG in preventing serum deprivation-induced PC12 cell apoptosis.     

Kinase inhibitors for cardiovascular disease

Over the last decade, there has been substantial progress toward understanding the pathophysiology and treatment of cardiovascular diseases (CVDs). Elucidating cellular responses to the extracellular environment and signal transduction mechanisms have provided the opportunity to explore novel molecular therapeutic approaches for the treatment of CVDs. Neurohormonal stimulation has been implicated in these diseases; blockade of the renin-angiotensin and beta-adrenergic systems are examples of therapeutic effectiveness. There are multiple cell signaling cascades, some of which are beneficial or compensatory and others deleterious. The balance between these pathways, which in large part is dictated by the cellular environment, determines the outcome as a diseased or non-diseased state. Selective targeting of signaling pathways using protein kinase inhibitors, would have a potential advantage over receptor blockers. We review potential protein kinase targets and recent evidence supporting therapeutic interventional value in CVDs.     

广西、海南、云南微小按蚊3种同工酶谱比较研究

目的　探索我国微小按蚊复合体同工酶谱鉴别指标。　方法　选择广西微小按蚊 (A .m .G)、海南微小按蚊(A .m .H)和云南微小按蚊 (A .m .Y)的单雌线雌蚊匀浆 ,采用不连续性聚丙烯酰胺凝胶垂直板状电泳法分离 ,特异性底物染色 ,比较观察乳酸脱氢酶 (LDH)、醇脱氢酶 (ADH)和酯酶 (EST) 3种同工酶谱。　结果　三地微小按蚊的LDH同工酶谱相同 ,均具 1条Rm14酶带 ;ADH酶谱中三地微小按蚊均显一条酶带 ,A .m .G与A .m .H具相同酶带Rm 3 4,而A .m .Y则是 1条Rm 40酶带 ;EST的主带谱A .m .G与A .m .H基本相似 ,前者显示Rm18、3 5和 61,后者显示Rm18、3 5、5 9和 61。而A .m .Y明显不同于A .m .G和A .m .H ,显示Rm18、3 9、43、5 0、5 6和 5 9六条主带。　结论　ADH和EST同工酶谱在不同种的微小按蚊中存在明显差别 ,可能在区别我国微小按蚊姐妹种中有较大的应用价值。     

小檗碱抑制机械牵张力诱导的小鼠血管平滑肌细胞PKCδ磷酸化及增殖/迁移

目的 观察机械牵张力(SS)是否通过激活PKCδ诱导小鼠血管平滑肌细胞(VSMC)增殖和迁移,并进一步探究小檗碱(BBR)对其的影响及作用机制.方法 体外常规培养小鼠VSMC分为6组:阴性对照组(NC)、小檗碱组(BBR)、PKCδ抑制剂Sotrastaurin组(Sotras)、SS组、SS+BBR组和SS+Sotr...     

Chemoprevention of liver cancer by plant polyphenols

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.     

Pharmacologic therapy for diabetic retinopathy

Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular oedema (ME) or proliferative diabetic retinopathy (PDR). ME is manifest by retinal vascular leakage and thickening of the retina. The hallmark of PDR is neovascularisation (NV) – abnormal angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. Pharmacologic therapy aimed specifically at preventing vascular leakage and NV would be a welcome addition to the armamentarium. PDR and ME could be prevented by improved metabolic control or by pharmacologically blunting the biochemical consequences of hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non-enzymatic glycation or by protein kinase C [PKC] inhibition). The angiogenesis in PDR could be treated via growth factor (e.g., vascular endothelial growth factor [VEGF], insulin like growth factor-1 [IGF-1]) blockade, integrin (e.g., alpha-v beta-3) blockade, extracellular matrix alteration (e.g., with steroid compounds) or interference with intracellular signal transduction pathways (e.g., PKC and mitogen activated protein kinase [MAPK] pathway proteins). Some of these antiangiogenic agents may also prove useful for treating or preventing ME. Numerous potentially useful antiangiogenic compounds are in development; two drugs are presently in clinical trials for treatment of the preproliferative stage of PDR, while two are in clinical trials for treatment of ME.