肺癌中相关凋亡分子的新近研究进展

在机体内细胞凋亡与细胞增殖共同维持组织的稳态,凋亡过程的紊乱在癌症发生、发展中起到重要的作用。肿瘤涉及凋亡通路中多种分子的改变,包括Bcl-2家族蛋白的改变、死亡受体的改变及胱天蛋白酶活性的改变等。凋亡通路中重要凋亡分子的缺失或抑制是导致肿瘤对治疗不敏感的重要因素,试图通过重新激活这些通路的新的治疗方案正在研究中。该文就肺癌中相关凋亡蛋白的新近研究进展予以综述。     

Astragalosides IV inhibits high glucose-induced cell apoptosis through HGF activation in cultured human tubular epithelial cells

Astragaloside IV (ASI) in Radix Astragali is believed to be the active component. The study aims to investigate whether ASI inhibits tubular epithelial cells apoptosis induced by high glucose and its mechanisms. Tubular epithelial cells in this paper were isolated from human kidney. The cells apoptosis was detected by TUNEL and caspase 3 assay. The protein levels of HGF and TGF-β1 were measured by ELISA. The phospho-p38 production, ERK and JNK were determined by Western blot. ASI could inhibit cells apoptosis induced by high glucose (25?mmol/L) in dose-dependent and time-dependent manners. ASI also inhibited high glucose-induced expression of TGF-β1 and activation of p38 MAPK pathway at the protein level. Furthermore, ASI increased HGF production in human tubular epithelial cells. The ASI inhibition of tubular epithelial cells apoptosis and reduction of TGF-β1 expression induced by high glucose may represent a new treatment for diabetic kidney injury. The mechanism underlying this inhibitory effect may be related to the inhibition of p38 MAPK signaling pathway activation and HGF overproduction.     

Circulating neutrophils exhibit enhanced apoptosis associated with mitochondrial dysfunctions after surgery under general anaesthesia

BACKGROUND: Evidence suggests that apoptosis plays a main role in the postoperative changes detected in the polymorphonuclear neutrophil (PMN) population. Furthermore, recent studies have demonstrated that mitochondrial alterations constitute critical events of the apoptotic cascade. In this study we investigated whether apoptosis among neutrophils taken from patients undergoing surgical trauma could be associated with perturbation of mitochondrial transmembrane potential (deltapsim) and/or exaggerated production of mitochondrial reactive oxygen species (ROS). METHODS: Twenty-seven patients undergoing elective surgery under general anaesthesia were enrolled in the study. Peripheral blood samples were drawn one day before the operation and at 12 and 24 h after surgery. Apoptosis rate was assessed by staining neutrophils with 7-amino-actinomycin D (7-AAD) and by analysis by a FACScan flow cytometer. In order to evaluate deltapsim, cells were exposed to 3,3-dihexyloxacarbocyanine iodide [DiOC6(3)]; intracellular ROS was measured by means of hydroethidine (HE) and 2,7-diclorofluorescein diacetate (DCFH-DA), followed by analysis on a cytofluorometer. RESULTS: At 12 h following surgery we observed a significantly (P<0.05) increased frequency of apoptotic PMNs compared to that preoperatively (30.79+/-3.68% vs 7.40+/-0.69%). At this same time-point, the rate of neutrophils stained with HE, DCFH-DA and [DiOC6(3)] were significantly (P<0.05) higher compared to baseline (51.05+/-5.44%, 50.58+/-5.84% and 55.31+/-4.33% vs 20.17+/-2.38%, 19.59+/-2.03 and 25.43+/-2.71% respectively). Overall measurements returned to the preoperative values 24 h after surgery. CONCLUSION: These data suggest that surgery under general anaesthesia triggers in the immediate postoperative period pathways of PMN accelerated apoptosis associated with significant alterations in mitochondrial function.     

大鼠脑外伤后神经细胞凋亡与Bcl-2蛋白的关系

目的研究大鼠外伤性脑挫裂伤细胞周围水肿带细胞凋亡随出血时相点的变化规律，以及脑挫裂伤后神经细胞凋亡和Bcl-2的关系．为脑挫伤的治疗提供理论依据。方法将健康Wistar大鼠随机分成6组，10只为对照组，50只为实验组，设置为6小时、24小时、3天、5天、7天共5个时相点．术后制作冰冻切片。用末端脱氧核糖转移酶介导的生物素化脱氧尿嘧啶缺刻标记技术（TUNEL技术）和免疫组化法（SP法1观察凋亡细胞和Bcl-2蛋白的表达．．结果在正常脑组织中bcl-2表达为阴性。损伤早期细胞凋亡与bcl-2表达明显增加，随着伤后时间延长．凋亡细胞伤后第3天达到高峰．而Bcl-2表达5天达到峰值。结论细胞凋亡与Bcl-2蛋白表达在一定时间窗内持续升高，但不同步，两者无明显线性关系．表明了bcl-2基因的抑制细胞凋亡作用。     

凋亡抑制蛋白Livin在人原发性肝癌细胞系HEPG-2中的表达情况

目的研究凋亡抑制蛋白Livin在人原发性肝癌细胞系HEPG-2中的表达情况。方法以RT-PCR法检测人原发性肝癌细胞系HEPG-2中凋亡抑制蛋白Livin基因mRNA的表达。结果HEPG-2细胞只表达Livin基因的β亚型,即Livinβ。结论人原发性肝癌细胞系HEPG-2细胞阳性表达Livinβ基因。本实验研究结果为原发性肝癌的诊断和治疗提供了新思路、新方法。