间歇性低压缺氧预处理对大鼠全脑缺血/再注后海马神经元的保护作用

目的 探讨间歇性低压缺氧预处理对大鼠全脑缺血/再注后海马神经元的保护作用.方法 72只健康雄性Wistar大鼠,体重280～300g,随机分为6组,每组12只.分别为假手术组(Sham);间歇性低压缺氧预处理组(IHHP);缺血/再灌注组(I/R);间歇性低压缺氧预处理2次+全脑缺.血/再灌注组( IHHP2+ I/R);间歇性低压缺氧预处理4次+全脑缺血/再灌注组(IHHP4+I/R);间歇性低压缺氧预处理6次+全脑缺血/再灌注组(IHHP6+ I/R).采用四血管闭塞法复制大鼠全脑缺血/再灌注模型,全脑缺血后8 min行再灌注.硫堇染色观察海马CA1区组织学分级及锥体神经元密度;流式细胞技术检测海马神经元凋亡率.结果 与Sham组相比,单纯性间歇性低压缺氧预处理对海马组织形态和神经元凋亡率均无明显影响;I/R组大鼠海马CA1区组织损伤明显,存活的锥体细胞稀疏,排列紊乱,细胞明显缺失.I/R组与Sham组相比,组织学分级明显升高,神经元凋亡率明显增加;间歇性低压缺氧预处理2次、4次和6次+ I/R各组大鼠海马CA1区细胞损伤均明显改善,组织学分级明显降低,存活神经元密度值均明显增加,神经元凋亡率明显降低,其中IHHP4+ I/R组效果最为明显.结论 间歇性低压缺氧本身对大鼠海马神经元无明显损伤作用,但可对其后短期内发生的缺血/再灌注脑组织发挥保护作用,适当的预处理是诱导有效脑保护作用发生的必要条件.     

川芎嗪预处理对大鼠肝缺血再灌注损伤能量代谢的保护作用

目的探讨川芎嗪预处理对大鼠肝脏缺血再灌注损伤(IRI)后肝脏能量代谢的影响。方法将120只雄性Wistar大鼠随机分为假手术组、实验组和对照组3组,实验组和对照组制作70%大鼠肝脏IRI模型,实验组大鼠在IRI前3d,每日腹腔注射川芎嗪注射液2mL,各组大鼠分别于术后1h、6h、24h、72h取肝组织观察组织形态学变化,检测肝细胞线粒体呼吸控制率(RCR)、磷氧比(P/O)和肝组织三磷酸腺苷(ATP)含量变化。结果①术后各个相应时相点实验组肝组织病理损伤均较对照组轻;②术后1h、6h、24h对照组肝细胞线粒体RCR及P/O均低于实验组(P均<0.05),72h均恢复正常(P>0.05);③实验组术后各相应时相点肝细胞ATP含量均高于对照组(P<0.05),并且恢复正常也比对照组较早。结论川芎嗪预处理能够改善肝脏能量代谢,提高缺血再灌注后肝脏的抗损伤能力。     

不同方式缺氧预处理对心肌细胞线粒体的影响

目的研究不同缺氧方式预处理对心肌细胞线粒体功能的影响,为探讨心肌缺血缺氧病理生理过程中的一些现象提供依据。方法原代培养乳鼠心肌细胞,经过几种不同的缺氧预处理后,继续培养24h,再次给予较严重的缺氧损伤处理,在不同钓时间点用用流式细胞仪检测罗丹明123标记线粒体的膜电位。结果Ⅰ组和Ⅱ组在缺氧预处理后的荧光强度通过成组t检验。t=10．16,P〈0．05;Ⅰ组和Ⅱ组在24h后再次经过缺氧损伤后荧光强度通过成组t检验,t=6．23,P〈0．05;Ⅰ组和Ⅲ组在缺氧预处理后的荧光强度通过成组t检验,t=34．12,P〈0．05;Ⅰ组和Ⅲ组在24h后再次经过缺氧损伤后荧光强度通过成组t检验,t=18．84．P〈0．05;Ⅰ组和Ⅳ组在缺氧预处理后的荧光强度通过成组t检验,t=26．25,P〈0．05;Ⅰ组和Ⅳ组在24h后再次经过缺氧损伤后荧光强度通过成组t检验,t=17．69,P〈0．05。再次损伤后Ⅱ组的细胞线粒体内的电位较对照组高。Ⅲ组和Ⅳ组的细胞线粒体内的电位明显较对照组低。结论在经过不同方式的缺氧预处理后,心肌细胞对再次严重缺氧损伤的反应性是不同的。预处理后的心肌细胞可以对再次损伤的抵抗力增强,即产生了我们所认识的预适应保护效应;也能产生心肌细胞对再次损伤的抵抗力减弱,即产生了我们所认识的缺氧损伤增敏效应。     

Dexmedetomidine Preconditioning Attenuates Cisplatin-Induced Ototoxicity in Zebrafish

Objectives

Utilisation of high-frequency drills is known to increase noise induced hearing loss due to increasing the damages of inner ear cells. This study aimed to investigate whether preconditioning by using dexmedetomidine (DEX) decreased the occurrence of ischemia in inner cells of the ear.

Methods

We utilised a transgenic zebrafish line Brn3C, and the embryos were collected from breeding adult zebrafish. Five-day-old larvae were cultured at the density of 50 embryos, and the larvae were classified into 4 groups: control, cisplatin group, DEX group, and DEX+yohimbine; adrenoreceptor blocker group. The DEX group was categorised into 3 subgroups by dosage; 0.1, 1, and 10 µM. Preconditioning was performed for 150 minutes and then exposed to cisplatin for 6 hours. The experiment was performed in 7 replicates for each group and the number of hair cells in 3 parts of the neuromasts of each fish was determined.

Results

Hair cell apoptosis by cisplatin was attenuated more significantly in the DEX preconditioning group than in the control group. However, the preconditioning effects were not blocked by yohimbine.

Conclusion

The results of this study suggest that hearing loss caused by vibration-induced noise could be reduced by using DEX and may occur through other mechanisms rather than adreno-receptors.     

“预处理”策略对Ⅱ型糖尿病患者围术期心肌保护作用的研究进展

糖尿病是心血管疾患的独立危险因素,糖尿病患者发生急性心肌梗死后的病死率明显升高.缺血预处理（IPC）、缺血后处理（IPOST）、远端肢体/组织预处理（RIC）以及麻醉药物预处理（APC）等“预处理”策略,已被证明在非糖尿病患者能够发挥明显的心肌保护作用,近年有研究认为,在Ⅱ型糖尿病患者其心肌保护作用被减弱或者消失.现就“预处理”技术对Ⅱ型糖尿病患者缺血性心肌损害的保护作用及其机制的研究进展予以综述.     

Activation of aldehyde dehydrogenase 2 (ALDH2) confers cardioprotection in protein kinase C epsilon (PKC?) knockout mice

Acute administration of ethanol can reduce cardiac ischemia/reperfusion injury. Previous studies demonstrated that the acute cytoprotective effect of ethanol on the myocardium is mediated by protein kinase C epsilon (PKC?). We recently identified aldehyde dehydrogenase 2 (ALDH2) as a PKC? substrate, whose activation is necessary and sufficient to confer cardioprotection in vivo. ALDH2 metabolizes cytotoxic reactive aldehydes, such as 4-hydroxy-2-nonenal (4-HNE), which accumulate during cardiac ischemia/reperfusion. Here, we used a combination of PKC? knockout mice and a direct activator of ALDH2, Alda-44, to further investigate the interplay between PKC? and ALDH2 in cardioprotection. We report that ethanol preconditioning requires PKC?, whereas direct activation of ALDH2 reduces infarct size in both wild type and PKC? knockout hearts. Our data suggest that ALDH2 is downstream of PKC? in ethanol preconditioning and that direct activation of ALDH2 can circumvent the requirement of PKC? to induce cytoprotection. We also report that in addition to ALDH2 activation, Alda-44 prevents 4-HNE induced inactivation of ALDH2 by reducing the formation of 4-HNE-ALDH2 protein adducts. Thus, Alda-44 promotes metabolism of cytotoxic reactive aldehydes that accumulate in ischemic myocardium. Taken together, our findings suggest that direct activation of ALDH2 may represent a method of harnessing the cardioprotective effect of ethanol without the side effects associated with alcohol consumption.     

肝脏及肢体缺血预处理抗大鼠肝缺血再灌注损伤的实验研究

目的研究肝脏缺血预处理(经典缺血预处理IPC)的第一保护窗(FW)与肢体缺血预处理(远端缺血预处理RPC)的第二保护窗(SW)及两者联合应用对大鼠肝脏缺血再灌注(I/R)损伤的保护作用及可能机制。方法大鼠随机分成5组:I/R组不行预处理;IPC组以肝缺血5 min行预处理;RPC组以双后肢缺血5 min,反复3次行预处理;RPC+IPC组先行RPC,24 h后行IPC作预处理;S组仅行开腹,不行其他处理。3个预处理组及I/R组均行肝缺血1 h再灌注3 h。取血用于血清谷丙转氨酶(ALT)与血清谷草转氨酶(AST)检测。切取肝组织用于测定肿瘤坏死因子α(TNF-α)和热休克蛋白70(HSP70)的表达、湿干比(W/D)及观察显微、超微结构的变化。结果与I/R组比较,IPC组,RPC组及RPC+IPC组ALT,AST,W/D及TNF-α阳性表达均明显降低(P0.01),HSP70表达量明显增加(P0.01),肝脏的显微及超微结构损伤减轻;IPC,RPC,RPC+IPC组3组间各项指标差异无统计学意义(P0.05)。结论IPC的FW,RPC的SW及两者联合应用对大鼠肝脏I/R损伤均有明显的保护作用,三者在保护强度上无明显差异。其机制可能与抑制TNF-α的产生、诱导保护性蛋白HSP70的表达、减轻肝脏水肿、改善肝组织微循环有关。     

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases

Background and aimsPreconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility.Materials and methodsThis was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant.ResultsMedian and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15–42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression.ConclusionSimultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.     

预处理化疗增强CIK细胞对Lewis肺癌的抑制作用

目的 观察预处理化疗在小鼠Lewis肺癌模型中对细胞因子诱导的杀伤细胞(cytokine - induced killer cells,CIK cells)的抗肿瘤活性的增强作用,并探讨介导此增效作用的机制.方法 建立C57BL/6小鼠Lewis肺癌模型,以紫杉醇( Paclitaxel,PTX)联合顺铂(Cispla...     

异丙酚和咪唑安定预处理对大鼠全脑缺血损伤的保护及递质机制

目的阐明异丙酚及咪唑安定预处理是否具有脑保护作用及其神经递质机制。方法雄性SD大鼠18只,随机分组,每组6只。建立清醒全脑缺血模型(4血管闭塞法)。收集清醒、缺血及再灌注后微透析标本。记录再灌注后的BIS变化,并观察反正反射恢复的时间。于缺血再灌注后进行运动功能双盲评定。全脑缺血3d后,迅速开颅取脑,10%甲醛固定后进行HE染色,并用TUNEL法进行细胞凋亡检测。双盲计数海马CA1区神经细胞及细胞凋亡率。结果异丙酚及咪唑安定预处理组与对照组相比,脑电BIS恢复较快;缺血期间谷氨酸递质浓度明显降低(P<0.01);反正反射恢复时间明显缩短(P<0.05);海马CA1区神经细胞计数明显增高(P<0.01);海马细胞凋亡率明显降低(P<0.01);两预处理组间无明显差异(P>0.05)。结论异丙酚及咪唑安定预处理脑缺血再灌注损伤具有脑保护作用,与减少缺血期间谷氨酸递质的释放有关;两组脑保护效能相同。