开郁健脾益胃汤对胃溃疡大鼠细胞凋亡的影响

目的观察开郁健脾方益胃汤对胃溃疡大鼠胃黏膜细胞凋亡及BCL-2蛋白表达的影响,探讨其机制。方法以乙酸烧灼法建立胃溃疡模型,观察用药后胃黏膜细胞凋亡及BCL-2蛋白表达。结果益胃汤能显著提高胃溃疡黏膜组织BCL-2蛋白的表达,TUNEL检测结果显示能明显减少细胞凋亡。结论益胃汤对胃溃疡有明显的保护作用,其机制可能是通过抑制胃溃疡黏膜组织细胞凋亡而发挥作用。     

PDCD5与BCL-2在多发性骨髓瘤中的表达

目的研究促凋亡基因PDCD5和抑凋亡基因BCL-2在多发性骨髓瘤中的表达情况.方法免疫组化及逆转录-聚合酶链反应方法(RT-PCR)检测31例及25例正常对照骨髓单个核细胞中PDCD5和BCL-2蛋白及mRNA的表达,用统计软件分析其表达水平之间的关系.结果MM组PDCD5阳性细胞率(%)和染色强度指数(SⅡ)均显著低于对照组,BCL-2阳性细胞率(%)和SⅡ显著高于对照组,PDCD5蛋白和BCL-2蛋白阳性细胞率(%)呈负相关(r=-0.86,P＜0.05).MM组PDCD5 mRNA的相对表达水平显著低于对照组,BCL-2 mRNA的相对表达显著水平高于对照组,PDCD5、BCL-2 mRNA表达水平呈负相关(r=-0.90,P＜0.05).结论MM患者骨髓单个核细胞中,PDCD5蛋白、mRNA表达下调,而BCL-2蛋白、mRNA上调,二者表达水平呈负相关.     

BH3类似物促细胞凋亡机制及临床研究进展

靶向细胞凋亡是目前癌症治疗中最具发展前景的治疗方法之一。BCL-2家族的BH3-only蛋白(仅含BCL-2同源结构域BH3)可以通过与家族中促存活蛋白结合,使促存活蛋白失效,从而使促凋亡成员发挥作用,最终导致细胞发生程序性凋亡。BH3类似物即一类可以模仿BH3-only蛋白并诱发细胞凋亡的小分子化合物。BH3类似物的原型ABT-737可以选择性靶向BCL-XL、BCL-2和BCL-W 3个促存活蛋白(但不能作用于髓细胞白血病因子-1蛋白或A1蛋白),而它的衍生物ABT-263(navitoclax)在临床试验中有显著的促凋亡与抗肿瘤效应。现阶段,一些推测为BH3类似物的药物已经进入了临床阶段,但很大一部分仍在进行特征鉴定。本文在概述BH3-only蛋白作用机制的基础上,综述了多种已经广泛认可的BH3类似物及正在研究当中的最新BH3类似物。     

膀胱尿路上皮癌组织Livin和BCL-2的表达及其相关性研究

目的 探讨Livin与BCL-2在膀胱尿路上皮癌及癌旁组织中的蛋白表达水平及二者在膀胱尿路上皮癌中的相关关系,分析其致癌机制,为膀胱尿路上皮癌的诊断及临床治疗提供理论依据.方法 用流式细胞分析技术检测90例膀胱尿路上皮癌及对应的90例癌旁组织,及20例正常膀胱粘膜移行上皮组织中的Livin、BCL-2蛋白的表达.90例膀胱尿路上皮癌中,男66例,女24例,年龄26~68(平均50.24±9.87)岁.按照WHO病理分级:G124例,G240例,G326例;TNM临床分期诊断标准:非浸润性癌(Ta-1期)38例,浸润性癌(T2-4期)52例;单发48例,多发42例;初发54例,复发36例;20例正常对照为前列腺增生症、膀胱结石患者经膀胱手术所取膀胱黏膜组织,均经病理检查证实为正常膀胱黏膜组织.将表达结果进行分析.结果 Livin在正常膀胱组织中不表达.于癌旁组织中亦无表达.Livin在膀胱尿路上皮癌组织中阳性率为71.11%,其中阳性64例,阴性26例.Livin的蛋白表达与细胞的凋亡率呈负相关.BCL-2阳性表达结果 膀胱癌癌组织(51.11%)与癌旁组织(73.33)BCL-2的表达差异有显著性 (P<0.05).90例膀胱尿路上皮癌中46例BCL-2蛋白表达阳性,阳性率为51.11%,与正常膀胱粘膜阳性表达率10%比较,阳性率明显上升(P<0.05).Bcl-2的蛋白表达与细胞的凋亡率呈负相关.在膀胱尿路上皮癌中Livin与BCL-2表达有密切关系 ,在膀胱癌BCL-2的表达随着膀胱肿瘤的分化程度越差阳性表达就增加 ,而 Livin蛋白的表达亦明显增加 ,呈现正相关 (P<0.05).结论 细胞凋亡抑制因子Livin在膀胱尿路上皮癌组织中表达上调,并且与凋亡率呈负相关,提示Livin可能通过抑制细胞凋亡,对膀胱尿路上皮癌的发生、发展起重要作用,有望成为一种有效、敏感的肿肿瘤标志物志物,并为膀胱尿路上皮癌的基因治疗提供新的靶点.Livin与BCL-2在膀胱尿路上皮癌细胞凋亡的调控方面可能起着协同作用.     

通冠胶囊后适应对大鼠心肌缺血再灌注损伤的保护作用及机制的研究

目的 通过制备大鼠心肌缺血再灌注模型,并在此基础上研究通冠胶囊不同剂量后适应以及缺血后适应方法对大鼠心肌梗死程度、心肌细胞凋亡状况的影响及作用机制.方法 采用结扎心脏左前降支的方法制备大鼠心肌缺血再灌注模型,并随机分为6组.实验结束后每组半数行NBT染色法及称重法测定心肌梗死范围;半数进行免疫组化法测定BCL-2蛋白及BAX蛋白表达;并行TUNEL染色测定凋亡指数;心尖部心肌组织测MDA及SOD水平.结果 与SO组相比较,各组的梗死范围均明显增加(P<0.01),表明心肌缺血再灌注模型成功.与I/R组相比较,IPC组与通冠胶囊HD组均可明显降低心肌梗死范围(P<0.01);SO组仅个别细胞凋亡;I/R组凋亡的心肌细胞明显增加,通冠胶囊LD组凋亡的心肌细胞数量也较多,呈弥漫分布;IPC组、通冠胶囊MD组、HD组凋亡的心肌细胞数减少,IPC组、通冠胶囊MD组、HD组凋亡细胞呈散在分布;与IR组相比,IPC组、通冠胶囊MD组、HD组凋亡细胞教减少,差异有统计学意义(P<0.05),IPO1组与IPO2两组相比差异有统计学意义(P<0.05).与SO组相比较,其余各组反应心肌氧化损伤的心肌组织脂质过氧化产物MDA含量增加,SOD活性降低,差异有统计学意义(P<0.01);与IR组相比,IPC组、MD组、HD组心肌MDA含量下降、SOD活性升高,差异有统计学意义(P<0.05);与SO组相比较,其余各组BCL-2及BAX蛋白表达均明显上升,差异有统计学意义(P<0.01).IPC组、MD组及HD组BCL-2蛋白表达均高于IR组(P<0.01);IPc组BAX蛋白表达低于IR组(P<0.01).结论 通冠胶囊后适应的心肌保护作用可通过降低局部氧自由基生成,升高BCL-2蛋白表达,提高BCL-2/BAX比值,抑制心肌细胞凋亡实现.通冠胶囊后适应可部分起到模拟缺血后适应的作用,且作用程度与剂量具有相关性.     

Bcl-2抑制剂维奈克拉在B细胞淋巴瘤中的治疗进展

BCL-2是调节细胞凋亡的关键蛋白，在很多血液系统恶性肿瘤中高表达，发挥抗凋亡作用。维奈克拉是首个高度选择性的BCL-2抑制剂，在全球范围内其第一个适应证为慢性淋巴细胞白血病（CLL），目前临床研究更已拓展到多种B细胞淋巴瘤、骨髓增生异常综合征（MDS）等多个血液肿瘤。本文对维奈克拉在B细胞淋巴瘤中的治疗进展作一综述。     

PTEN、BCL-2和C-erbB-2蛋白在子宫内膜癌的表达及临床意义

目的探讨检测PTEN、BCL-2和C-erbB-2蛋白在子宫内膜癌中表达的临床意义。方法采用免疫组化S-P法,分别检测20例正常子宫内膜组织、20例子宫内膜癌前病变、50例术后子宫内膜癌组织标本中PTEN、BCL-2和C-erbB-2蛋白的表达情况。结果 （1）子宫内膜癌组织与子宫内膜癌前病变、正常子宫内膜组织比较,PTEN、BCL-2蛋白阳性表达率明显降低,差异有显著性,C-erbB-2蛋白阳性表达率明显增加,差异有显著性。（2）PTEN蛋白与BCL-2蛋白的表达与组织学分级及临床分期均有关,且随着组织学分级和临床分期的升高,PTEN蛋白及BCL-2蛋白的阳性表达均显著降低;与有无淋巴结转移均无关。（3）C-erbB-2蛋白的表达与临床分期有关,随着临床分期的增加,C-erbB-2蛋白的阳性表达显著升高;与组织学分级及淋巴结转移无显著相关。（4）在子宫内膜癌中,PTEN与BCL-2蛋白的表达呈正相关,而PTEN与C-erbB-2蛋白的表达呈负相关,BCL-2与C-erbB-2蛋白的表达呈负相关。结论 PTEN、BCL-2蛋白失表达和C-erbB-2蛋白过表达在子宫内膜癌的发生、发展中发挥着一定的作用,三者的联合检测可能有助于子宫内膜癌的早期诊断、预后评估。     

Effect of aldosterone receptor antagonist on cardiomyocyte apoptosis and the expression of Bcl-2,Bax protein in rats

目的 研究醛固酮受体拮抗剂螺内酯对急性心肌梗死心肌细胞凋亡及相关基因Bcl-2、Bax蛋白表达的作用.方法 通过结扎左冠状动脉前降支造成大鼠左室大面积心肌梗死模型.SD大鼠随机分为心肌梗死对照组(AMI组,0.9%氯化钠溶液2ml/d灌胃,n=24)和螺内酯治疗组(Spi组,螺内酯20 mg/kg/d,2ml灌胃,n=24),另设假手术组(Sham组,0.9%氯化钠溶液,2 ml/d灌胃,n=24).分别于术后2、7、14、21 d观察下列指标:用流式细胞学方法测定非梗死心肌细胞凋亡率及Bcl-2、Bax蛋白表达.结果 与Sham组相比较,AMI组大鼠和Spi组非梗死区心肌细胞凋亡率显著升高(P<0.01);BCL-2蛋白表达降低(P<0.05),Bax蛋白表达升高(P<0.05);与AMI组比较,大鼠心肌细胞凋亡率和非梗死区心肌细胞BCL-2蛋白表达在2 d、7 d差异无统计学意义(P>0.05),14 d、21 d有所升高(P<0.05).Bax蛋白表达在2 d、7 d差异无统计学意义(P>0.05),14 d、21 d有所降低(P<0.05).结论 螺内酯治疗可减少心肌细胞凋亡,同时增加凋亡相关基因Bcl-2蛋白的表达和减弱Bax蛋白的表达.     

醛固酮受体拮抗剂对心肌细胞凋亡的影响

目的研究醛固酮受体拮抗剂螺内酯对急性心肌梗死心肌细胞凋亡及相关基因Bcl-2、Bax蛋白表达的作用。方法通过结扎左冠状动脉前降支造成大鼠左室大面积心肌梗死模型。SD大鼠随机分为心肌梗死对照组(AMI组,0.9%氯化钠溶液2ml/d灌胃,n=24)和螺内酯治疗组(Spi组,螺内酯20mg/kg/d,2ml灌胃,n=24),另设假手术组(Sham组,0.9%氯化钠溶液,2ml/d灌胃,n=24)。分别于术后2、7、14、21d观察下列指标:用流式细胞学方法测定非梗死心肌细胞凋亡率及Bcl-2、Bax蛋白表达。结果与Sham组相比较,AMI组大鼠和Spi组非梗死区心肌细胞凋亡率显著升高(P<0.01);BCL-2蛋白表达降低(P<0.05),Bax蛋白表达升高(P<0.05);与AMI组比较,大鼠心肌细胞凋亡率和非梗死区心肌细胞BCL-2蛋白表达在2d、7d差异无统计学意义(P>0.05),14d、21d有所升高(P<0.05)。Bax蛋白表达在2d、7d差异无统计学意义(P>0.05),14d、21d有所降低(P<0.05)。结论螺内酯治疗可减少心肌细胞凋亡,同时增加凋亡相关基因Bcl-2蛋白的表达和减弱Bax蛋白的表达。     

治疗慢性淋巴细胞白血病新药——BCL-2抑制剂venetoclax

BCL-2是细胞凋亡信号途径中的重要靶分子,发挥抑制细胞凋亡的作用。venetoclax为一种口服选择性BCL-2抑制剂,通过与BCL-2结合,恢复肿瘤细胞的正常凋亡途径,从而发挥抗肿瘤的作用。venetoclax已获美国FDA批准用于单独治疗曾接受过至少一种治疗方案的染色体17p缺失的慢性淋巴细胞白血病患者。其常见的不良反应包括中性粒细胞减少、腹泻、恶心、贫血、血小板减少、上呼吸道感染及疲劳等。     

The effect of interleukin-10 on apoptosis in macrophages stimulated by oxLDL

Marked anti-atheromatous effects of the anti-inflammatory cytokine interleukin-10 (IL-10) were observed in several lipid-driven animal models of arteriosclerosis. We have previously demonstrated that IL-10 significantly inhibited lipid uptake in macrophages induced by oxLDL (Wang et al., 2008; Yang et al., 2008b). In this study, we investigated whether IL-10 affects the apoptosis related gene BCL2L11 and BMF expression in macrophages treated with oxLDL from THP-1 cells, which served as macrophage models. Cell apoptosis assays were performed by flow cytometry. Expression of the apoptosis related genes BCL2L11 and BMF mRNA was quantified by real-time RT-PCR (mRNA expression) and Western blotting (protein expression). IL-10 markedly blocked oxLDL induced cells undergoing early stage apoptosis. In the foam cell group, as compared with the macrophage group, the percentage of apoptosis increased by 100%. Here the expression of BCL2L11 was 45% (mRNA) and 41% (protein) elevated, while the expression of BMF was 54% (mRNA) and 44% (protein) elevated. When macrophages were co-stimulated by 100mg/l oxLDL and 20 μg/l IL-10 for 24h, compared with the foam cell group, the percentage of the apoptosis decreased by 21%, the expression of apoptosis related gene BMF was inhibited, the expression of mRNA and protein was both depressed by 23% and 20%, respectively, but the BCL2L11 expression was unchanged. These results may explain why decrement of early stage apoptosis cells was observed during co-stimulation and raise the possibility that IL-10 reduces foam cell undergoing apoptosis partly through down-regulating the expression of BMF, which demonstrates a critical role of IL-10 in anti-atherogenesis.     

Effect of benzyl chloride on rat liver functions

Benzyl chloride (BCL) is extensively used in industry for the manufacture of dyes, perfumes, and pharmaceutical products. A previous study from this laboratory revealed the presence of liver steatosis of the microvesicular type and central focal inflammation in rats following the inhalation of BCL. This study was conducted to investigate the hepatotoxicity of intravenous (iv) BCL in rat. BCL (250, 25, and 0 micrograms/kg) was administered (iv) to rats, and serum enzyme tests were used to evaluate hepatic injury. After 10 min from BCL administration, serum glutamic-pyruvic transaminase and lactic dehydrogenase activities were significantly increased compared to the control group, while the values returned to normal within 1 h from the administration of BCL. Also, ornithine carbamyltransferase enzyme activity was significantly increased and reached a maximum as early as 0.5 h from the administration of BCL. Hepatic excretory function was investigated by the clearance of bromosulfophthalein (BSP) after 0.5 and 24 h from the administration of BCL. The clearance of BSP in both treatments was significantly slower compared to control group throughout the 24 h studied. Furthermore, BCL significantly decreased liver and blood glutathione values. This study revealed that BCL has the potential to cause hepatomalfunction.     

Naringin Protects against Rotenone-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells

Rotenone, a mitochondrial complex I inhibitor, can induce the pathological features of Parkinson''s disease (PD). In the present study, naringin, a grapefruit flavonoid, inhibited rotenone-induced cell death in human neuroblastoma SH-SY5Y cells. We assessed cell death and apoptosis by measuring mitogen-activated protein kinase (MAPKs) and caspase (CASPs) activities and by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Naringin also blocked rotenone-induced phosphorylation of Jun NH2-terminal protein kinase (JNK) and P38, and prevented changes in B-cell CLL/lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) expression levels. In addition, naringin reduced the enzyme activity of caspase 3 and cleavages of caspase 9, poly (ADP-ribose) polymerase (PARP), and caspase 3. These results suggest that naringin has a neuroprotective effect on rotenone-induced cell death in human neuroblastoma SH-SY5Y cells.     

五味子甲素协同吉西他滨抑制肝癌细胞HepG2增殖

目的探究五味子甲素(deoxyschizandrin)联合吉西他滨(gemcitabin,GEM)对肝癌细胞HepG2增殖的影响及其可能的作用机制。方法CCK8法和克隆平板实验检测五味子甲素单药、GEM单药及联合用药对肝癌细胞HepG2增殖能力的影响;流式细胞术检测单药组及联合用药组中HepG2细胞的凋亡比例;Western blot法检测各组细胞中BCL2、BAX、pro-caspase3、cleaved-caspase3、pro-caspase9、cleaved-caspase9、β-catenin和TCF-4的表达。结果五味子甲素、GEM及联合用药对细胞HepG2的增殖均具有抑制作用,促进其凋亡,且联合用药组对HepG2细胞的作用明显强于单药组(P<0.05);Western blot结果表明,与对照组相比,五味子甲素、GEM和联合用药对pro-caspase3、pro-caspase9表达无明显影响,显著减少BCL2、β-catenin及TCF-4蛋白的表达(P<0.05),上调BAX、cleaved-caspase3、cleaved-caspase9蛋白的表达(P<0.05)。其中,联合用药比单药更为显著(P<0.05)。结论五味子甲素协同GEM抑制肝癌细胞HepG2中β-catenin/TCF-4通路,进而减少细胞增殖,诱导其凋亡。     

Long non-coding RNA SNHG15 is a competing endogenous RNA of miR-141-3p that prevents osteoarthritis progression by upregulating BCL2L13 expression

Increasing evidence has demonstrated that the dysregulated expression of long noncoding RNAs (lncRNAs) has important roles in the progression of osteoarthritis (OA), but the function of the lncRNA SNHG15 remains unclear. In the present study, we observed that SNHG15 was downregulated in OA cartilage tissues and IL-1β-induced chondrocytes. The lower expression of SNHG15 was negatively associated with the observed modified Mankin scale scores, extracellular matrix (ECM) degradation and chondrocyte apoptosis. Downregulated expression of SNHG15 increased chondrocyte viability and decreased chondrocyte apoptosis and ECM degradation in vitro and reduced damage to articular cartilage in vivo. Mechanistically, we demonstrated that SNHG15 overexpression promotes the expression of BCL2L13 by sponging miR-141-3p. The higher expression of miR-141-3p was negatively correlated with SNHG15 and BCL2L13 levels in OA cartilage tissues, and a positive correlation was also shown between SNHG15 and BCL2L13 levels. Furthermore, ectopic expression of miR-141-3p or knockdown of BCL2L13 expression could both reduce the effects of SNHG15 on chondrocyte proliferation, apoptosis and ECM degradation. Collectively, these findings reveal that SNHG15 inhibits OA progression by acting as an miR-141-3p sponge to promote BCL2L13 expression, suggesting that knockdown of SNHG15 expression in chondrocytes can be a potential therapeutic strategy to ameliorate OA progression.     

Quercetin attenuates cadmium-induced oxidative damage and apoptosis in granulosa cells from chicken ovarian follicles

The attenuating effect of quercetin on cadmium-induced oxidative damage and apoptosis was investigated in cultured granulosa cells from chicken ovarian follicles. Results showed that exposure to 5 μM CdCl(2) induced a decrease in granulosa cell number and viability, caused chromatin condensation and DNA fragmentation. Moreover, cadmium treatment markedly increased malondialdehyde level and decreased glutathione peroxidase and superoxide dismutase activities. Furthermore, cadmium provoked higher BAX expression, inhibited expression of BCL2 and X-linked inhibitor of apoptosis protein (XIAP) and activated caspase-3. However, simultaneous supplementation with 1 μg/ml quercetin protected granulosa cells against cadmium-induced cytotoxicity through attenuating lipid peroxidation, renewing antioxidant enzymes activities and alleviating apoptosis by modulating XIAP, BAX and BCL2 expression, and inhibiting caspase-3 activity. Therefore, these results suggested that quercetin, as a widely distributed dietary antioxidant, contributes potentially to prevent cadmium-induced cytotoxicity in granulosa cells through attenuating lipid peroxidation, elevating intracellular antioxidant status and inhibiting apoptosis to ensure reproductive health.     

慢性铅中毒对海马BCL2表达的影响

为研究 BCL2表达在铅引起学习记忆障碍中的作用 ,给 Wister大鼠饮用不同剂量的醋酸铅 80天 ,用跳台法检测其学习记忆能力 ,用免疫组化法测定 BCL2表达水平。结果显示 ,慢性染铅可导致大鼠学习记忆障碍 ,BCL2作为重要的神经细胞凋亡调控因子参与了这一毒害过程。     

Low concentration arsenite activated JAK2/STAT3 signal and increased proliferative factor expressions in SV‐HUC‐1cells after short and long time treatment

Epidemiological studies have indicated that ingestion of inorganic arsenic resulted in increased risks of bladder cancer and chronic hyperproliferation could play a direct role in the development of cancer. This study examined the effects of arsenite on JAK2/STAT3 pathway and expressions of proliferation and anti‐apoptosis factors. The results showed that long term exposure to low doses arsenite enhanced human uroepithelial cells (SV‐HUC‐1 cells) proliferation and BrdU positive rate was significant increased. mRNA and protein expressions of proliferation factors, such as cyclin D1, COX‐2, and proliferating cell nuclear antigen (PCNA), increased in chronically exposed arsenite SV‐HUC‐1 cells with exposure time. Furthermore, JAK2/STAT3 signal pathway was activated following exposure to arsenite in SV‐HUC‐1 cells. Knockdown of STAT3 reduced expressions of cyclin D1, COX‐2, PCNA, and BCL2 induced by arsenite. In conclusion, arsenic induced proliferation in human uroepithelial cells after short and long term exposure to arsenite and JAK2/STAT3 signaling pathway might be pivotal in arsenite‐induced proliferation by regulating cyclin D1, COX‐2, PCNA, and BCL2.