Protecting spermatogonia from apoptosis induced by doxorubicin using the luteinizing hormone-releasing hormone analog leuprorelin

PURPOSE: The present study was performed to investigate the protective effect of leuprorelin (LH-RH analog), on spermatogonia apoptosis induced by doxorubicin (DXR) in the Sprague-Dawley rat model. METHODS: Twenty-four adult male rats were divided into the following four groups: (i) control group; (ii) group given doxorubicin (intravenous injection, 8 mg/kg); (iii) group given leuprorelin (subcutaneous injection, 3 mg/kg); and (iv) group given both doxorubicin (intravenous injection, 8 mg/kg) and leuprorelin (subcutaneous injection, 3 mg/kg). Evaluation for quantification of apoptotic spermatogonia was made by the ratio of TUNEL-labeled spermatogonia versus 100 Sertoli cells in each seminiferous tubule. Two hundred seminiferous tubules of each rat were assessed. RESULTS: The ratio of apoptotic spermatogonia versus 100 Sertoli cells at stages II-IV of the groups given DXR (groups 2 and 4) were significantly higher than those of the other groups. However, the value at stages II-IV of the group given both DXR and leuprorelin (group 4) was significantly lower than that of the group given DXR (group 2). CONCLUSION: The significant prophylactic effect (P < 0.05) of LH-RH analog against doxorubicin-induced spermatogonial apoptosis was observed in a stage specific manner by microscopic evaluation with TUNEL.     

UVA对人角质形成细胞的氧化损伤作用

①目的　探讨紫外线A(UVA)对人角质形成细胞氧化损伤的机制。②方法　用 5J/cm2 UVA照射角质形成细胞 ,酶生化法检测活性氧 (ROS)的含量及超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH PX)活性的变化 ,流式细胞仪测定紫外线对角质形成细胞凋亡的影响 ,原位杂交技术观察 p2 1mRNA的变化 ,并与非照射组比较。③结果　与对照组比较 ,UVA照射组ROS含量升高 (t =113.6 8,P <0 .0 0 1) ,SOD、GSH PX活性下降 (t =5 7.2 3、19.0 4 ,P <0 .0 0 1) ,细胞凋亡率升高 (t=5 3.2 8,P <0 .0 0 1) ,p2 1mRNA表达增强。④结论　UVA对人角质形成细胞的损伤与氧自由基生成增多及细胞抗氧化能力抑制有关     

SB203580对肾缺血/再灌注损伤时细胞凋亡及p38MAPK影响的实验研究

目的　探讨不同时间及不同浓度p38MAPK特异性抑制剂SB2 0 35 80对肾缺血 /再灌注损伤过程中肾功能、细胞凋亡及 p38MAPK活性、表达量、p38MAPK底物的影响。 方法　 4 9只大鼠按缺血 /再灌注及给药时间的不同 ,随机分为 7组 ,每组7只大鼠按正交拉丁方表的顺序 ,经尾静脉注射相同体积、不同剂量的SB ,使其在大鼠体内达到不同的浓度。测定BUN和Scr;用TUNEL试剂盒检测细胞凋亡情况 ;Westernblot技术用于蛋白定性及半定量分析。结果　SB可显著减轻大鼠肾缺血 /再灌注损伤造成的Scr和BUN的升高、肾小管上皮细胞的凋亡及 p38MAPK的激活 ,但存在模型、剂量及给药时机的差异 (P<0 .0 5 ) ,缺血前 3h之前给药 ,使其体内血药浓度达到 5 μmol/L左右可取得较好的效果。 结论　SB可显著减轻大鼠肾缺血 /再灌注损伤 ,在缺血前 3h之前给药 ,同时使其血药浓度达到 5 μmol/L左右可取得最佳效果。     

海带多糖的抗辐射作用与脾细胞凋亡

目的 :探讨海带多糖 (LJP)抗辐射作用及其可能机理。方法 :将Wistar大鼠随机分为正常对照组、模型组和 4个不同剂量LJP实验组 ,灌胃 1 0d后行一次性γ射线辐射 ,每只 9.0Gy ,1 8h后测定各组大鼠体液免疫、细胞免疫、非特异性免疫相关指标及脾淋巴细胞凋亡率。结果 :模型组免疫指标明显低于正常对照组 ,LJP各组能显著调节辐射损伤大鼠的免疫功能 ,脾淋巴细胞凋亡率显著低于模型组 ,并呈现明显的剂量 效应关系。结论 :LJP抗辐射作用的可能机理之一是抑制免疫细胞凋亡     

Apopotic gene Bax expression in carotid plaque

The expression of BAX in carotid atherosclcrosis and its regulation is far from defined. Objectives To investigate BAX expression in stable/fibrous and instable/vulnerable carotid plaque and its clinical significance. Methods 25 cases of carotid plaque specimens obtained from endarterectomy were divided into two groups, stable/fibrous 14 cases, vulnerable/instable 11 cases; aortic artery and its branches from hepatic transplantation donors 6 case as control. The expression of proapoptotic BAX was detected by immunohistochemistry (IHC), in situ hybridization(ISH) and in situ TdT dUTP nick end labeling (TUNEL). Results 5 eases of BAX ( ) were detected by ICH and ISH, 4 case of TUNEL ( ) were detected by TUNEL in stable/fibrous carotid plaque, while 10 cases were BAX ( )by IHC(P<0.05) , 11 case by ISH and 9 case by TUNEL were detected in instable/vulnerable carotid plaque (P<0.01), respectively. The intensity of BAX ( ) cells by IHC and ISH was 8.63±2.62 and 10.32±3.12 in fibrous plaques, whereas 122±21.64 and 152±23.35 in vulnerable plaques, respectively. No expression of BAX was found in controlled group. Conclusion The higher expression of Bax in vulnerable carotid plaque may be one mechanisms in molecular pathogenesis of carotid atherosclerosis which affect plaque stability and be the cause of higher incidence of stroke than fibrous carotid plaques, the regulation of BAX expression in different stage of atherosclerosis may provide targets in gene therapy for carotid atherosclerosis.     

异黄酮对PC-3细胞凋亡的诱导作用

目的 :　通过观察染料木素 (genistein,GS)、大豆甙元 (daidzein,DA)和黄豆黄素(glycitein,GL)对前列腺癌细胞 (PC- 3 )凋亡的影响 ,探讨通过膳食途径预防前列腺癌发生危险性的可行性。方法 :　将 PC- 3细胞在 RPMI1 6 4 0培养液 (含 1 0 %小牛血清 )中采用开放式单层贴壁培养。实验设溶剂对照及三种受试物各三个剂量组 ,采用流式细胞术 ,DNA凋亡片段凝胶电泳和细胞 HE染色法分析三种常见异黄酮类物质对 PC- 3细胞凋亡的影响。结果 :　与对照组相比 ,流式细胞仪分析结果表明 ,5 0μ mol/L GS、75μ mol/L DA和 75μ mol/L GL对 PC- 3细胞处理 72 h,二倍体细胞 (G1期细胞 )相对减少 ,亚二倍体细胞峰 (即细胞凋亡率 )逐渐增多 ,即凋亡细胞比例逐渐增多 ;DNA凋亡片段凝胶电泳和细胞苏木素染色结果也显示 ,三种受试物能够诱导 PC- 3细胞凋亡 ,且这种作用存在剂量 -效应关系。结论 :　异黄酮类化合物染料木素、大豆甙元和黄豆黄素均具有诱导 PC- 3细胞凋亡的作用 ,这一结果提示 ,该类物质是可通过诱导细胞凋亡而发挥其抗肿瘤作用的。     

系统性红斑狼疮患者淋巴细胞亚群早期凋亡的初步研究

目的：检测系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中不同细胞亚群发生凋亡的情况，并初步分析其在SLE发病机制中的意义。方法：取28例SLE患者和性别年龄与之相匹配的20个正常对照者。采用淋巴细胞亚群标志、Annexin-V及碘化丙啶三色荧光标记、流式细胞术检测细胞的早期凋亡。结果：SLE患者体内CD3^ T细胞、CD4^ T细胞和CD8^ T细胞的凋亡百分率均显著高于正常对照组(P＜0．05)。同时，SLE患者T淋巴细胞的死亡百分率也高于正常人。经激素治疗一定时间后，这些细胞亚群的凋亡率会进一步升高(P＜0．01)，但CD4／CD8比值恢复至接近正常人。SLE患考体内CDl9^ B淋巴细胞的凋亡或死亡百分率和正常对照组相比均无明显差别，激素治疗对B细胞凋亡和死亡的影响亦不显著。结论：在SLE患者体内主要是T淋巴细胞凋亡增加，但SLE患者淋巴细胞数目减少不仅仅是因为细胞凋亡所致，死亡细胞数目明显升高也是其中一个重要原因。激素治疗可诱导SLE患者T淋巴细胞进一步发生凋亡，并使T细胞亚群比例有所改善。     

宫颈鳞癌中erbB3、erbB4基因蛋白表达与细胞凋亡和增殖的相关性研究

目的　探讨原癌基因erbB3、erbB4与细胞凋亡和增殖的关系 ,为该基因作用机制提供新线索。方法　分别采用免疫组化、DNA末端标记技术 (TUNEL法 )和HE染色检测 5 0例宫颈鳞癌中erbB3、erbB4基因蛋白表达及凋亡指数 (AI)和增殖指数 (MI)。结果　宫颈鳞癌中erbB3、erbB4表达率分别为 5 2 .5 %、44 .0 % ,AI、MI值分别为 5 .5 0± 4.10和 4.18± 3 .63 ,随着宫颈癌恶性程度增高、FIGO分期进展、肿瘤体积的增大和淋巴结转移组 ,erbB3、erbB4表达率增加 ,AI、MI值也增高 ,但差异仅在分化程度上有显著性 (P <0 .0 5 )。双变量相关分析显示erbB3、erbB4表达与AI、MI间无相关性 (r3=0 .10 98、0 .12 3 6,r4 =0 .2 15 1、0 .2 5 5 8,P >0 .0 5 )。结论　erbB3、erbB4和AI、MI预示着宫颈癌恶性潜能 ,但不能作为预后有用指标。erbB3、erbB4的作用机制可能不是通过细胞凋亡或增殖起作用     

鼻息肉上皮细胞凋亡与bcl-2的表达及意义

目的　了解细胞的凋亡和癌基因bcl 2在鼻息肉的发病机制中的作用。方法　应用免疫组织化学的方法检测 45例鼻息肉细胞凋亡早期蛋白 (M3 0 )和bcl 2的表达 ,用下鼻甲粘膜作自身对照。结果　鼻息肉上皮和下鼻甲粘膜上皮的M3 0指数分别为 0 482± 0 3 2 ;1 0 62± 0 5 47,其差别有统计学意义 (P <0 0 1)。bcl 2阳性细胞在鼻息肉表层上皮和腺上皮均有表达 ,在下鼻甲中未见表达 ,其指数为 14 5 1± 4 46。结论　鼻息肉的发病机制及其生长过程与上皮细胞的增殖和凋亡的失平衡有关。bcl 2的表达可能是鼻息肉上皮凋亡抑制的原因 ,在鼻息肉上皮细胞增殖和凋亡失平衡的过程中起重要作用     

Apoptosis in perinatal hypoxic-ischaemic cerebral damage

Perinatal hypoxia-ischaemia induces a biphasic cerebral injury: the depletion in high energy phosphates during the insult returns to normal soon after resuscitation. However, some 8–15 h later a second phase of impaired energy metabolism begins, which is related to the severity of later neurodevelopmental impairment. Delayed injury differs from acute hypoxia-ischaemia because intracellular acidosis does not occur. Apoptosis may be a mechanism of delayed cellular injury. Apoptotic cells and typical DNA fragmentation have been found after perinatal hypoxia-ischaemia. In newborn piglets, fraction of apoptotic cells was directly related to the degree of high energy phosphate depletion during hypoxia-ischaemia. Apoptosis may be interrupted: in piglets, brain cooling for 12 h following resuscitation reduced the fraction of apoptotic but not necrotic cells. These results have implications for both the understanding of cerebral injury and the use of hypothermia as a neural rescue strategy in the developing brain.