Bcl-2 GENE REARRANGEMENT DETERMINED BY PCR AS AMEAN TO DETECT MINIMAL RESIDUAL DISEASE INMALIGNANT LYMPHOMAS

Objective: To develop a sensitive method to detect minimal residual disease and to elucidate the significance of bcl-2 gene rearrangement in diagnosis and treatment of malignant lymphoma. Methods: Using polymerase chain reaction (PCR) to detect bcl-2 gene rearrangement and using serial dilution method to define the sensitivity of PCR. Results: In 9 different malignant lymphoma cell lines, Su-DHL-4 and Su-DHL-6 were shown bcl-2(MBR)/JH rearrangement, the sensitivity of PCR was 1:105. In 16 patients with follicular lymphoma, the peripheral blood and bone marrow were PCR positive in 4 cases both at initial diagnosis and after complete remission. Conclusion: Detection of bcl-2 gene rearrangement by PCR provides a sensitive and specific assay of minimal residual disease. It is helpful to improve staging of disease, prognosis and evaluation of the treatment results.

Study on the Regulation of Bcl-2 Gene on Rat Spermatogenic Cells Apoptosis in Transcription Level

Objective To detect the change of Bcl 2 gene expression in the apopototic process of spermatogenic cells in rat with vasoligation and vasostomy, and to find out the relationship between the transcription of Bcl 2 and the apoptosis of spermatognic cells Materials & Methods Sixty adult male Sprague Dawley rats in 3 groups were operated with vasoligation and vasostomy. Then hybridization in situ with hypersensitive Bcl 2 RNA probe was used to detect the change of Bcl 2 mRNA. Results The transcription of Bcl 2 gene in spermatogenic cells was obviously inhibited in the vasoligation group compared with that in the control group (P<0.05), and the transcription in the vasostomy group showed no difference from that of the control group. Conclusion Bcl 2 gene has an anti apoptotic effect in rats with vasostomy, and there was a transcriptional regulation of Bcl 2 gene in rat spermatogenic cell during the period of pre vasoligation to post vasoligation and to post vasosotomy.

DETECTION OF BCL-2 GENE MAJOR BREAKPOINT REGION REARRANGEMENT IN HUMAN B-CELL LYMPHOMAS

Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of B-cell lymphomas were studied uslng DNA extracted from rresh-frozen tissues. The DNA samples were amplified by PCR for bcl-2 MBR/JH. The products of bcl-2/JH rearrangement were hybridized with an internal olignucleotide probe or bcl-2 MBR. Results The rearranged bcl-2MBR/JH gene was detected in 13 of the 25(52. o% ) follicular center lymphomas, according to REAL classification: 8 of 11 (72. 7%) grade 1, 2 of 5(40. 0%) grade I, and 3 of 90 (33. 3%) grade, 17 of 82(2o. 8%) cases or difruse large B-cell lymphomas were found to have detectable bel-2 MBR/J. rearrangement- Conclusion The rrequency or bcl-2 MBR/JH rearrangement in diffuse large B-cell lymphomas is significantly lower than those in follicular center lympkomas(X2= 9. 28, P <o. oo5), suggesting that bcl2/JH rearrangements occur mainly in follicular center lymphomas. in addition, the result of reconstruction experiments suggest that amplification or bcl-2 MBR/JH rearrangements by PCR is both sensitive and specific for detection of t (14; 18 ) translocation.

THE EXPRESSION OF BCL-2 GENE AFTER TRANSIENT FOCAL ISCHAEMIA AND THE EFFECT OF MK-801

in order to clarify the pesible role of the bcl-2 gene imolved in the cell death Program,and the relatiouship of glutamate receptors with bcl-2 gene expressin, this study examied the expression of bcl-2 gene protein, the neuronal status of apoptosis and the effects of MK-801 using immunohistochemistry and in situ terminal.labelling methods after 30 min of.middle cerebral artery(MCA) occlusion and followed by 24 h of reperfusion. The presence of bcl-2 gene protein increased in the ipeilateral hemisphere of ischaemis espeially in the MCA territory MK-801 enhanced the expresion of the bcl-2 gene protein. No DNA fragmentation was detected in this experiment. In conclusion. bcl-2 gene activity increased during transient focal ischaemia, and was potentiated by MK MK801, which may be an endogenous protective mechanism .against ischaemic apoptosis. Apoptosis wasnot detected after tranient focal ischoemia. for 30 min rollowed by 24 h of reperfusiou.

Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival

BACKGROUND: Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas- mediated cell death and to prolong recipient survival. METHODS: Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft. RESULTS: Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group. CONCLUSION: Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.

Expression of the bcl-2 gene and its significance in human pancreatic carcinoma

Objective: To elucidate the expression of the bcl-2 gene in association with both biological characteristics of hu- man primary pancreatic carcinoma and patient's prog- nosis. Methods: The s-p immunohistochemistry assay was used to detect the expression of the bcl-2 gene on para- ffin-embedded sections from 97 cases of primary pan- creatic carcinoma, 32 cases of pancreatitis, and 21 ca- ses of normal pancreas. Results: Among the 97 cases of pancreatic carcinoma, 70 (72.2%) showed positive staining for the bcl-2 pro- tein. In the 32 cases of pancreatitis, 3 (9.4%) showed positive immunostaining for the bcl-2, and in the nor- mal pancreas cases, 1 (4.8%) showed positive immu- nostaining for the bcl-2. However, the positive staining rates of the bcl-2 protein were lower in tumor tissue from the patients with metastases and tumor-node-me- tastasis (TNM) stages Ⅲ, Ⅳ than in those from those with non-metastases, well differentiation, non-invasion and TNM stages Ⅰ, Ⅱ. The patients with positive im- munostaining of bcl-2 have a longer postoperative sur- vival than those with negative staining. Conclusions: Pancreatic carcinoma expressed a high positivity for bcl-2. Findings suggested that the overex- pression of bcl-2 is related to the carcinogenesis and progression of human pancreatic carcinoma. Bcl-2 might be one of the parameters in terms of biological characteristics and good prognosis in patients with pancreatic carcinoma.

Study of the expressions of p53 and bcl-2 genes, the telomerase activity and apoptosis in GIST patients

AIM: To explore the relationship between clinicobiological behavior and the expression levels of telomerase activity, apoptosis, p53 gene and bcl-2 gene in gastrointestinal stromal tumors (GISTs). METHODS: The intensity of telomerase activity, apoptosis, p 53 and bcl -2 expression in GISTs were detected by telomeric repeat amplification protocol, in situ end-labeling technique, and immunohistochemistry, respectively. RESULTS: The positive rates of telomerase activity of malignant GIST, potential malignant GIST and benign GIST were 85% (17/20), 22.8% (2/9) and 0 (0/9), respectively. The apoptosis indices of malignant GIST, potential malignant GIST, and benign GIST were 11.7 ± 5.4, 30.2 ± 5.6 and 45.2 ± 7.2, respectively. The intensity of telomerase activity and apoptosis were related to the biological characteristics of GISTs (85% vs 22.8%, 0, 0; P < 0.01 or 11.7 ± 5.4 vs 30.2 ± 5.6, 45.2 ± 7.2, 72.1 ± 9.3; P < 0.05). The intensity of telomerase activity was negatively correlated with cellular apoptosis (22.9 ± 8.4 vs 9.5 ± 5.7, P < 0.01). The intensity of telomerase activity was positively correlated with p53, bcl-2 expression (40.0% vs 78.9%, 40.0% vs 84.2%; P < 0.05). CONCLUSION: The detection of telomerase activity, apoptosis and its control genes in GIST will be helpful for the discrimination of the malignant and benign GIST and evaluation of the prognosis.

THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group（ 10％ O2, 8h/d） and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling（ TUNEL） technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT- PCR were used to detect the expression level of bcl- 2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT- PCR, we found the expression of bcl- 2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bcl- 2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

Effects of Bcl-2 Gene Interference on the Apoptosis,Proliferation and Progesterone Secretion of Goose Follicular Granulosa Cells

Based on published sequences for chicken Bcl-2,three siRNAs（small interfering RNA）were designed,and expression vectors were constructed and transfected into goose granulosa cells cultured in vitro.Bcl-2 protein,apoptosis and proliferation of granulosa cells,48 h after the transf ection,were analyzed by flow cytometry,and progesterone（P）secreted into the culture medium was measured by radioimmunoassay.In addition,apoptosis and Bcl-2 protein level were assessed in untreated granulosa cells from the four largest preovulatory follicles（F1F4）,the smallest preovulatory follicles（SPF）,small yellow follicles（SYF）and atretic follicles.The highest level of Bcl-2 protein was observed in granulosa cells from SPF,and levels in cells from healthy follicles were significantly higher than those of atretic follicles（P【0.05）.Bcl-2 protein levels in cells subjected to RNAi were significantly lower than those of controls（P【0.05）,while apoptosis indices（AI）,proliferation indices（PI）and P secretion in the RNAi treatments were higher than those of controls（P【0.05）.

Silencing of Bcl-2 gene expression by siRNA transfection in- hibits the protective effect of fluvastatin against cell apoptosis in human aortic endothelial cells

Objective To study the protective effect of fluvastatin,one of the HMG-CoA reductase inhibitors (statins),against oxygen radical-induced oxidative damages in human aortic endothelial cell,and the role of Bcl-2 in this protection.Methods Human aortic endothelial cells with or without Bcl-2 siRNA transfection were subjected to 1-100 nM of fluvastatin and 100 la hydrogen peroxide for 24 hours.Bcl-2 mRNA and protein expression were measured by Taqman quantitative PCR and Western blotting.Cell apoptosis was measured by normal and fluorescent microscopy and Cell Death Detection ELISA.Results In the Bcl-2-expressed cells,fluvastatin significantly reversed hydrogen peroxide-induced microscopic apoptosis and apoptotic DNA fragmentation,which were accompanied by a markedly upregulation of Bcl-2 expression by fluvastatin.However,the endothelial protection by fluvastatin was completely lost in Bcl-2 siRNA transfected cells.Conclusion Fluvastatin protects human endothelial cells against oxygen radical-induced cell apoptosis in vitro,and this protection seemed to be mediated in a Bcl-2 dependent pathway.(J Geriatr Cardil 12008;5:33-38)

The relationship between bcl-2 gene abnormality and nasopharyeal carcinoma

objective To explore the relationship between bcl--2 gene abnormality and nasopharyngeal carcinoma (NPC) Methods: bcl--2/JH fusion gene and bcl-2 protein expression were examined with semi--nested insitu PCR (SNISPCR) and immunohistochemistry technique in 41 NPC. Results: (l) Bcl-2/JH fusion genewere found in 6 cases of 41 NPC (positivity rate, 14. 6% ). (2)Bol-2 protein was expressed in 34 cases of 41NPC, the positivity rate being 82. 9 %. No bcl-2 expression was seen in benign nasopharyngeal lesions. Conclusion: (l) Translocation was not a specific change in lymphoma, but mbr and mcr regions are the two important breakpoint regions in NPC. Bcl-2/JH fusion gene formation may not play an important role in pathogenesis of NPC for its low positive rate. (2) There was no corresponding relationship between formation ofhcf-2/JH fusion gene and aberrant hcf-2 protein expression in NPC.

华蟾素对肝癌患者介入术后外周血Bcl-2和cyclinD1蛋白表达水平的影响

目的观察华蟾素对肝癌患者介入术后外周血Bcl-2和细胞周期蛋白(cyclinD1)表达水平的影响。方法本次研究对象在2020年5月—2021年5月于医院进行介入术治疗的肝癌患者中选择100例,随机分为两组,50例患者给予患者常规介入治疗(常规介入组),50例患者在常规化疗的基础上加用华蟾素治疗(华蟾素组)。检测患者的Bax、Bcl-2、cyclinD1水平及肝功能指标[甲胎蛋白(AFP)、谷丙转氨酶(ALT)、总胆红素(TBIL)、谷草转氨酶(AST)]、免疫功能指标[免疫球蛋白G(IgG)、自然杀伤(NK)细胞、T淋巴细胞亚群(CD_(4)^(+)、CD_(4)^(+)/CD_(8)^(+))],比较两组卡氏(KPS)评分、肝功能分级标准(Child-Pugh)评分,评价疗效,观察两组不良反应发生情况。结果华蟾素组患者治疗后的Bax水平高于常规介入组(P<0.05),Bcl-2、cyclinD1水平低于常规介入组(P<0.05);华蟾素组患者治疗后的AFP、TBIL、AST水平低于常规介入组(P<0.05),ALT水平高于常规介入组(P<0.05);华蟾素组患者治疗后的IgG、NK细胞、CD_(4)^(+)水平高于常规介入组(P<0.05),CD_(4)^(+)/CD_(8)^(+)水平低于常规介入组(P<0.05);华蟾素组患者治疗后的KPS评分高于常规介入组(P<0.05),Child-Pugh评分低于常规介入组(P<0.05);华蟾素组患者治疗有效率为92.00%,高于常规介入组的74.00%(P<0.05);华蟾素组患者的不良反应发生率为20.00%,低于常规介入组的44.00%(P<0.05)。结论华蟾素可以下调肝癌患者介入术后外周血Bcl-2和cyclinD1蛋白表达水平,上调Bax水平,促进肿瘤细胞凋亡;同时可以增强患者的肝功能和免疫功能,提高生活质量,改善预后;还能提高肝癌介入治疗疗效,降低发生不良反应的风险。

电针对骶上脊髓损伤后神经源性膀胱大鼠尿流动力学及脊髓组织ERK/CREB/Bcl-2通路表达的影响

目的观察电针“次髎”“中极”“三阴交”“大椎”对骶上脊髓损伤后神经源性膀胱大鼠尿流动力学及脊髓组织ERK/CREB/Bcl-2通路表达的影响。方法60只雌性SD大鼠随机选取24只分为空白组和假手术组各12只,其余36只采用脊髓横断法造模,将成模大鼠随机分为模型组和电针组,每组12只。电针组取单侧“次髎”“中极”“三阴交”“大椎”进行电针刺激,每次30 min,1次/d,连续7 d。干预结束后行尿流动力学检测,HE染色观察大鼠膀胱逼尿肌组织形态,TUNEL法检测脊髓组织细胞凋亡情况,Western blot测定脊髓组织p-ERK1/2、p-CREB、p-p90Rsk、CRE、Bcl-2、Bax蛋白表达。结果与假手术组比较,模型组大鼠膀胱基础压力、最大压力及漏尿点压明显增加(P<0.01),膀胱最大容量及顺应性明显降低(P<0.01);膀胱平滑肌细胞结构严重破坏、排列紊乱,伴大量炎性细胞浸润;脊髓组织细胞凋亡率明显升高(P<0.01),脊髓组织p-ERK1/2、p-p90Rsk、p-CREB、CRE、Bcl-2蛋白表达明显降低,Bax蛋白表达明显升高(P<0.01)。与模型组比较,电针组大鼠膀胱基础压力、最大压力及漏尿点压均明显降低(P<0.05),膀胱最大容量及顺应性明显增加(P<0.05,P<0.01);膀胱平滑肌细胞完整性增强,细胞水肿程度降低,炎性细胞浸润减轻;脊髓组织细胞凋亡率明显降低(P<0.05),脊髓组织p-ERK1/2、p-p90Rsk、p-CREB、CRE、Bcl-2蛋白表达明显升高,Bax蛋白表达明显降低(P<0.05,P<0.01)。结论电针可促进骶上脊髓损伤后神经源性膀胱大鼠膀胱逼尿肌组织修复,增加膀胱最大容量及顺应性,缓解膀胱内高压状态,其机制与激活ERK/CREB/Bcl-2通路、减少受损神经元继发性凋亡、改善膀胱的神经支配、保护膀胱功能有关。

基于Caspase-3/Bcl-2/Bax信号通路探究加味旋覆代赭汤治疗食管癌前病变的作用机制

目的:探究加味旋覆代赭汤对食管癌前病变大鼠Caspase-3/Bcl-2/Bax信号通路的调控作用机制。方法:将48只雄性SD大鼠随机分为4组,空白组、模型组、中药组、西药组,每组各12只。除空白组外均采用复合造模法制作食管癌前病变大鼠模型,造模成功后,分别进行药物灌胃干预,空白组、模型组用生理盐水灌胃,中药组和西药组分别给予加味旋覆代赭汤、西药(雷贝拉唑+莫沙必利)灌胃,给药8周取材。利用光学显微镜观察食管上皮组织的形态学变化;分别应用蛋白质印迹法(Western-blot)及聚合酶链式反应(PCR)检测食管上皮组织Caspase-3、Bcl-2及Bax的表达水平。结果:与空白组比较,模型组大鼠食管上皮病理积分升高(P<0.01);与模型组比较,中药组、西药组大鼠食管上皮病理积分均降低(P<0.01)。PCR及Western-blot检测结果显示,与空白组比较,模型组大鼠Caspase-3、Bax mRNA、蛋白表达均降低(P<0.01);与模型组比较,中药、西药组大鼠Caspase-3、Bax mRNA、蛋白表达均增高(P<0.05)。与空白组比较,模型组大鼠食管组织中Bcl-2 m RNA及蛋白表达水平均升高(P<0.05);与模型组比较,中药组和西药组Bcl-2 mRNA及蛋白表达水平均降低(P<0.05)。结论:加味旋覆代赭汤可能通过下调Bcl-2/Bax比值,增加线粒体外膜通透性,释放凋亡因子,激活Caspase-3,使病变组织发生凋亡,扭转食管上皮异型增生,从而起到治疗食管癌前病变的作用。

从NF-κB/Bcl-2信号通路调控成纤维样滑膜细胞凋亡角度探讨中医药抑制类风湿关节炎滑膜炎症机制的研究进展

类风湿关节炎(rheumatoid arthritis,RA)是一种以关节滑膜炎症为主要特征的自身免疫性疾病,成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)的抗凋亡是导致该病病情发展的主要因素。如何促进FLS凋亡并抑制炎症反应是目前RA治疗和研究的重点。核因子κB(nuclear factor kappa-B,NF-κB)/B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)信号通路在RA发病过程中发挥了关键作用,其与FLS炎症倾向、抗凋亡等密切相关。研究并探讨NF-κB/Bcl-2信号通路调控FLS凋亡的机制及作用,介绍中医药靶向该通路促进FLS凋亡进而抑制RA滑膜炎症的研究现状,旨在为中医药治疗RA的研究提供一定基础。

乳腺癌患者病理特征与Bcl-2、CXCL13、PAX8表达情况的关系分析

目的分析乳腺癌患者病理特征与B细胞淋巴瘤/白血病-2基因(Bcl-2)、趋化因子配体13(CXCL13)、配对盒基因8抗体(PAX8)表达情况的关系。方法收集2021年1月至2023年1月该院收治的160例乳腺癌患者临床资料。采用免疫组化法对其癌组织与癌旁组织Bcl-2、CXCL13、PAX8表达情况进行检测,并分析3项指标与患者病理特征的关系。结果与癌旁组织比较,癌组织Bcl-2、CXCL13、PAX8阳性率更高,差异有统计学意义(P<0.05)。与雌激素受体(ER)阴性、肿瘤最大径≥3 cm、孕激素受体(PR)阴性患者比较,ER阳性、肿瘤最大径<3 cm、PR阳性患者中Bcl-2高表达占比更高,差异有统计学意义(P<0.05);与无淋巴结转移、Ⅰ~Ⅱ期患者比较,淋巴结转移、Ⅲ~Ⅳ期患者中CXCL13高表达占比更高,差异有统计学意义(P<0.05);与Ⅰ~Ⅱ期、高/中分化、无淋巴结转移患者比较,Ⅲ~Ⅳ期、低分化、有淋巴结转移患者中PAX8高表达占比更高,差异有统计学意义(P<0.05)。ER、PR表达情况与Bcl-2表达情况呈正相关(P<0.05),肿瘤最大径与Bcl-2表达情况呈负相关(P<0.05);临床分期、淋巴结转移情况与CXCL13、PAX8表达情况呈正相关(P<0.05);分化程度与PAX8表达情况呈负相关(P<0.05)。结论乳腺癌患者Bcl-2、CXCL13、PAX8表达情况对疾病的发生和发展具有明显影响,有望成为评估乳腺癌患者病情严重程度的标志物。

桂枝加龙骨牡蛎汤对魄不安于肺不寐大鼠脑组织Caspase-3、Bcl-2、Bax水平的影响

目的:探讨桂枝加龙骨牡蛎汤对魄不安于肺不寐大鼠脑组织Caspase-3、Bcl-2、Bax表达的影响及其治疗魄不安于肺不寐可能的作用机制。方法:32只雄性SD大鼠随机分为对照组、模型组、中药组和西药组,每组8只。采用水环境小平台法干预9 d建立魄不安于肺不寐大鼠模型,造模成功后,中药组予以桂枝加龙骨牡蛎汤7.6 g·kg-1·d-1灌胃,西药组予以右佐匹克隆片0.1 mg·kg-1·d-1灌胃,对照组和模型组给予等体积生理盐水灌胃,连续14 d,测量体质量。采用免疫组织化学法及蛋白质免疫印迹法检测脑组织中Caspase-3、Bcl-2、Bax表达水平。结果:与对照组比较,模型组大鼠体质量减轻(P<0.01),免疫组化检测结果显示,大鼠脑组织Bcl-2的表达显著减少(P<0.01),Caspase-3、Bax表达显著增加(P<0.01),Bcl-2/Bax比率显著减少(P<0.01);Western blot结果显示大鼠脑组织Bcl-2相对表达量显著减少(P<0.01),Bax、Caspase-3相对表达量显著增加(P<0.01)。与模型组比较,中药组及西药组大鼠体质量显著增加(P<0.01),免疫组化检测结果显示,大鼠脑组织Bcl-2表达增加(P<0.05),Caspase-3、Bax表达减少(P<0.05),Bcl-2/Bax比率显著升高(P<0.01);Western blot结果显示大鼠脑组织中Bcl-2相对表达量增加(P<0.05),Bax、Caspase-3相对表达量显著减少(P<0.01)。结论:桂枝加龙骨牡蛎汤改善魄不安于肺不寐大鼠的睡眠可能与增加其脑组织Bcl-2、降低Caspase-3、Bax表达水平有关。

红景天苷调控NF-κB、Bcl-2信号通路对烟雾暴露大鼠氧化应激及肺血管内皮细胞凋亡的影响

目的探究红景天苷(SDS)通过调控B淋巴细胞瘤-2(Bcl-2)、核转录因子-κB(NF-κB)信号通路对烟雾暴露大鼠氧化应激及肺血管内皮细胞凋亡的机制。方法选取60只大鼠分为对照组、模型组、SDS 10 mg/kg、SDS 40 mg/kg、SDS 70 mg/kg、醋酸泼尼松(PNS)组,每组10只,除对照组外,其余均建立烟雾致肺损伤模型,对照组与模型组大鼠每日采用等量生理盐水灌胃;SDS高、中、低剂量组分别按70、40、10 mg/kg剂量给予SDS混悬液2 mL灌胃;PNS组给予PNS混悬液3.6 mg/kg灌胃,均每日1次,连续21 d。结果与对照组比较,模型组大鼠血清中丙二醛(MDA)、Bcl-2相关X因子(Bax)、NF-κB、p-NF-κB及细胞凋亡升高,超氧化物歧化酶(SOD)、Bcl-2降低(P<0.05);与模型组比较,SDS各剂量组MDA、Bax、NF-κB、p-NF-κB及细胞凋亡均有所降低,SOD、Bcl-2也有所升高(P<0.05),且模型组与SDS 10 mg/kg组比较无明显差异(P>0.05),SDS 40 mg/kg组与PNS组比较无明显差异(P>0.05)。对照组大鼠肺组织良好;模型组肺损伤严重;药物干预后各组肺损伤均减轻。结论SDS可改善烟雾暴露大鼠肺损伤、氧化应激及血管内皮细胞凋亡,其机制可能与调控Bax/Bcl-2及NF-κB相关。