Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1–PI3K/AKT pathway

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.KEY WORDS: Cisplatin, DNMT, Apoptosis, Hair cell, Spiral ganglion neurons, RG108, Mitochondrial dysfunction, ROS     

高温联合辐射对仔鼠神经系统与行为的影响

目的探讨高温联合辐射对仔鼠神经系统与行为的影响。方法将130只孕鼠按随机抽签法分为13组,每组10只。在孕鼠妊娠第8、9d分别接受60Co及γ-射线全身照射各1次,照射剂量1．0Gy;第10d各置温箱中,分别使其肛温保持在37、±0．5℃,41±0．5℃,42±0．5℃,并持续3、4、5min。移出温箱2h后,每组随机取5只,单笼饲养,待其自然分娩,观察仔鼠体格发育、生理发育、神经反射、活动能力等神经行为指标。结果孕鼠经高温联合辐射后,其仔鼠的生理发育、早期反射、感觉功能、活动能力均显著滞后于对照组(P<0．01)。结论高温联合辐射具有复合作用,可增强对仔鼠神经系统的不良影响。     

首发精神分裂症患者IL-1β的血清蛋白水平及PBMC mRNA表达

目的从基因转录和蛋白水平,观察精神分裂症中IL-1β的动态变化情况,了解其免疫状态,并探讨IL-1β与精神病理的关系。方法采用病例对照研究方法,精神分裂症组为根据DSM—Ⅳ诊断为精神分裂症的本地汉族患者83例,单一应用利培酮治疗,在治疗前后评定PANSS量表;对照组为健康志愿者65例。应用ELISA和RT—PCR方法,同时检测血清IL-1β蛋白水平和PBMC中IL-1β mRNA表达。结果（1）精神分裂症组治疗前、后与对照组血清IL--1β水平相比,均明显增高,差异有显著性（P〈0．05）。精神分裂症组治疗后血清IL—-1β水平与治疗前相比明显下降,差异有显著性（P〈0．05）。（2）IL-1β治疗前后的差值与PANSS量表降分率呈显著正相关（r=0．388,P〈0．05）。（3）精神分裂症组治疗前、后PBMC中IL-1β mRNA表达与对照组相比明显增高,差异有显著性（P〈0．05）。精神分裂症组治疗后PBMC中IL-1β mRNA表达与治疗前相比明显下降,差异有显著性（P〈0．05）。结论（1）精神分裂症患者存在免疫激活,IL-1β水平的变化可作为病情缓解的一个灵敏指标。（2）精神分裂症患者PBMC呈激活状态,是IL-1β的主要来源之一,探讨影响PBMC细胞因子mRNA表达的因素,有助于反映对机体的免疫状况的影响。     

经尿道射精管切开术治疗射精管梗阻的效果(附60例报告)

目的：探讨经尿道射精管切开术（transurethral resection of ejaculatory duct, TURED）治疗射精管梗阻（ejaculatory duct obstruction, EDO）的效果。方法：2004年10月至2010年10月期间收治60例EDO患者,常规采用精液分析、精浆果糖和经直肠超声检查对其进行诊断,必要时行输精管造影检查。60例EDO患者均行TURED治疗,术后随访其疗效。结果：60例EDO患者的精液量为0.2~3.5 mL,平均(1.10±0.76) mL,pH值5.8~7.6,平均6.5±1.4;精浆果糖为一次射精0~51.4 μmol,平均为(5.86±2.19) μmol。经直肠超声检查结果为：单纯射精管扩张者15例,前列腺囊肿6例,单纯双侧精囊扩张10例,单侧精囊扩张4例,精囊扩张并射精管扩张10例,精囊扩张合并前列腺囊肿5例,单侧精囊扩张并对侧精囊发育不良或缺乏2例,精囊扩张并射精管扩张和钙化3例,单侧精囊扩张并射精管扩张和对侧精囊发育不良或缺乏5例。所有患者均完成手术,术后随访6~78个月。60例EDO患者行TURED术后,51例(85.0%)精液检查有不同程度的改善,16例(26.7%)妻子妊娠。结论：TURED是治疗EDO的一种简单、微创和有效的方法。     

糖性白内障大鼠晶状体水不溶性蛋白的改变

用D一半乳糖诱发了大鼠白内障,分析了其膜固有蛋白和尿素溶蛋白的改变。对正常大鼠晶状体纤维细胞膜蛋白电泳图谱的分析表明,其26KDa的主要膜固有蛋白(MIP26)约占膜固有蛋白总量的42.9％,22KDa的膜固有蛋白约占6.4％。糖性白内障大鼠晶状体纤维细胞膜固有蛋白以22KDa为主,约占30.5％,MIP26几乎消失。并在24KDa处有一深染区带。在白内障发病过程中18KDa的膜蛋白的相对含量无明显改变。这些结果提示在糖性白内障发病过程中MIP26发生了降解,产生了22KDa的降介产物。 以每克湿重计,白内障晶状体尿素溶蛋白降低约22.5％。但白内障晶状体尿素溶蛋白占总蛋白的比例升高。正常大鼠尿素溶蛋白电泳图谱主要显示四条区带,其近似分子量分别为22.5KDa、22.4KDa、20.6KDa和19.2KDa。白内障晶状体20.6KDa和19.2KDa的二条区带所占的比例明显减小。这个结果提示正常晶状体尿素溶蛋白主要含有α—和β—晶体蛋白,而且白内障晶状体尿素溶蛋白则主要含有β—晶体蛋白。     

黄芩甙大鼠小肠吸收的研究

本文作者对文献介绍的大鼠在体小肠回流实验装置进行了改进,并用来研究黄芩甙的吸收情况和胆管结扎与不结扎对黄芩甙吸收的影响。胆管结扎与不结扎的药动学参数为:平均吸收半衰期分别是15.45h~(-1)、11.42h~(-1)。最终吸收程度依次是24.44%,31.58%。经方差分析两者无显著差异(F<5.3)。     

Correlation of cell proliferation inhibition and apoptosis induction with expression of human beta 5 integrin on hematopoietic cells

OBJECTIVE To investigate the function of the alpha v beta 5 integrin in hematopoietic cells.

METHODS Tissue culture, integrin expression vectors, gene transfer, polymerase chain reaction (PCR), apoptosis analyses and cytometic analysis were made on hematopoietic cells.

RESULTS The beta 5 integrin cDNA was not expressed in hematopoietic cells following exposure to the beta 5 integrin retrovirus vector pG beta 5CHT. Unbalanced expression of the alpha v beta 3 and alpha v beta 5 integrins occurred during apoptosis induced by serum depletion and upon differentiation. The treatment of hematopoietic cells with anti-alpha v beta 5 monoclonal antibody inhibited apoptosis induced by serum depletion. Inducible expression of the beta 5 integrin cDNA in the hematopoietic cell line K562 caused cellular proliferation inhibition.

CONCLUSIONS The alpha v beta 5 integrin cDNA in hematopoietic cells can inhibit the proliferation of the hematopoietic cell, cause the differentiation of the hematopoietic cells and induce the apoptosis of the hematopoietic cells.

     

新生儿窒息后血清心肌肌钙蛋白I的检测及其意义

目的　探讨血清心肌肌钙蛋白I(cTnI)评估新生儿窒息后的心肌损害的临床价值。方法　采用ELISA法对 2 0例窒息新生儿和 2 5例正常新生儿进行cTnI检测 ,同时检测肌酸磷酸激酶同功酶 (CK -MB)。结果　窒息组急性期血清cTnI、CK -MB水平明显高于对照组 (P <0 .0 5 ) ,且窒息时间越长 ,血清cTnI、CK -MB水平升高越明显 ,cTnI诊断新生儿窒息后心肌损伤的特异性均优于CK -MB。结论　血清cTnI和CK -MB的测定有助于早期预测心肌细胞损害 ,cTnI优于CK -MB     

经胸超声心动图在经心导管封堵小儿房问隔缺损中的应用

目的探讨经胸超声心动图(TTE)在经心导管封堵小儿房间隔缺损(ASD)中的应用价值.方法TTE多个切面测量46例ASD最大直径,ASD部位及周围关系,术中TTE测量ASD球囊伸展径并与X线所测球囊伸展径比较,选择Amplatzer ASD封堵器的型号、引导封堵器的放置及疗效评价.结果46例经心导管封堵的ASD中40例封堵成功,6例因术中严重心律失常、Amplatzer ASD封堵器意外脱落、ASD太大和左房长径不足以及ASD距下腔静脉太近而未能封堵成功.TTE测ASD最大径(1.43±0.68)cm与X线所测球囊伸展径(1.66±0.82)cm高度相关,(r=0.89,P<0.01),TTE术中测球囊伸展径(1.78±0.85)cm与X线测球囊伸展径高度相关,(r=0.98,P<0.01).结论TTE能很好显示小儿ASD大小、部位及其周围关系,方法简便,无痛苦,在经导管封堵小儿ASD中具有重要作用.     

青年男性精索静脉曲张231例分析

收集2013年8月山东省某县兵检站征兵体检资料,参加应征人伍体检男青年共711人,年龄17～ 24岁,平均年龄18.3岁,诊断为精索静脉曲张231例,患病率32.49％(231/711),其中Ⅰ度5例(2.2％),Ⅱ度165例(71.4％),Ⅲ度54例(23.4％),查体前已手术治疗7例(3.0％).以上患病率明显高于文献资料记载,值得思考并进一步研究.