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| 1 | Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats显示文摘17β-estradiol(E2) has been shown to have neuroprotective effects in different central nervous system diseases. The mechanisms underlying estrogen neuroprotection in spinal cord injury(SCI) remain unclear. Previous studies have shown that autophagy plays a crucial role in the course of nerve injury. In this study, we showed that E2 treatment improved the restoration of locomotor function and decreased the loss of motor neurons in SCI rats. Realtime PCR and western blot analysis revealed that the protective function of E2 was related to the suppression of LC3 II and beclin-1 expression. Immunohistochemical study further confirmed that the immunoreactivity of LC3 in the motor neurons was down-regulated when treated with E2. In vitro studies demonstrated similar results that E2 pretreatment decreased the autophagic activity induced by rapamycin(autophagy sensitizer) and increased viability in a PC12 cell model. These results indicated that the neuroprotective effects of E2 in SCI are partly related to the suppression of excessive autophagy. | Chao-Wei Lin Bi Chen Ke-Lun Huang Yu-Sen Dai Hong-Lin Teng | 2016 | Neuroscience Bulletin2016，32，2： | 14 |
| 2 | Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury显示文摘Hydrogen can relieve tissue-damaging oxidative stress, inflammation and apoptosis. Injection of hydrogen-rich saline is an effective method for transporting molecular hydrogen. We hypothesized that hydrogen-rich saline would promote the repair of spinal cord injury induced by Allen's method in rats. At 0.5, 1, 2, 4, 8, 12 and 24 hours after injury, then once daily for 2 weeks, 0.25 m L/kg hydrogen-rich saline was infused into the subarachnoid space through a catheter. Results at 24 hours, 48 hours, 1 week and 2 weeks after injury showed that hydrogen-rich saline markedly reduced cell death, inflammatory cell infiltration, serum malondialdehyde content, and caspa se-3 immunoreactivity, elevated serum superoxide dismutase activity and calcitonin gene-related peptide immunoreactivity, and improved motor function in the hindlimb. The present study confirms that hydrogen-rich saline injected within 2 weeks of injury effectively contributes to the repair of spinal cord injury in the acute stage. | Jian-long Wang Qing-shan Zhang Kai-di Zhu Jian-feng Sun Ze-peng Zhang Jian-wen Sun Ke-xiang Zhang | 2015 | Neural Regeneration Research2015，10，6： | 12 |
| 3 | Dysfunctional autophagy in Alzheimer's disease: pathogenic roles and therapeutic implications显示文摘Neuronal autophagy is essential for neuronal survival and the maintenance of neuronal homeostasis. Increasing evidence has implicated autophagic dysfunction in the pathogenesis of Alzheimer's disease(AD). The mechanisms underlying autophagic failure in AD involve several steps, from autophagosome formation to degradation. The effect of modulating autophagy is context-dependent. Stimulation of autophagy is not always beneficial. During the implementation of therapies that modulate autophagy, the nature of the autophagic defect, the timing of intervention, and the optimal level and duration of modulation should be fully considered. | Jun-Hua Liang Jian-Ping Jia | 2014 | Neuroscience Bulletin2014，30，2： | 12 |
| 4 | 小剂量丙戊酸与拉莫三嗪联合治疗新诊断癫痫的临床疗效及安全性研究显示文摘目的观察小剂量丙戊酸与拉莫三嗪联合治疗新诊断癫痫的临床疗效及安全性。方法将102例患者随机分为观察组与对照组,两组患者病程均为3—12个月。于治疗前及治疗后3、6个月评估患者的发作频率、控制效果及不良反应发生情况,根据三种指标参数变化评估患者病情变化。结果小剂量丙戊酸与拉莫三嗪联合治疗新诊断癫痫的临床疗效优于单药治疗的效果;小剂量丙戊酸与拉莫三嗪联合治疗新诊断癫痫的不良反应略高于单药治疗,差异未见统计学的意义(P〉0.05)。结论小剂量丙戊酸与拉莫三嗪联合治疗新诊断癫痫的临床疗效优于单药用药的效果,且该治疗方法具有安全性,是一种值得推广的癫痫病临床治疗方法。 | 赵二会 | 2016 | 临床医学2016，36，5： | 11 |
| 5 | 细胞自噬在脊髓损伤中作用的研究进展显示文摘近年来,细胞自噬在脊髓损伤中的研究逐渐成为热点,但脊髓损伤后早期自噬激活所起的作用尚有争议。其原因在于细胞自噬在脊髓损伤中的作用具有两面性:一方面自噬能诱导自噬性细胞死亡的发生并参与细胞凋亡的发生,另一方面自噬能促进受损变性蛋白的代谢以及抑制细胞凋亡。然而究其对脊髓损伤后修复的利弊作用,早期自噬激活的程度具有决定作用,脊髓损伤后适当地上调自噬水平可促进受损变性蛋白的代谢并抑制细胞凋亡,而过度激活自噬可能引发自噬性细胞死亡。 | 周凯亮 张小磊 吴凯 王雍立 徐华梓 | 2015 | 中国骨伤2015，28，8： | 10 |
| 6 | Modulation of autophagy for neuroprotection and functional recovery in traumatic spinal cord injury显示文摘Spinal cord injury(SCI) is a serious central nervous system trauma that leads to loss of motor and sensory functions in the SCI patients. One of the cell death mechanisms is autophagy, which is ‘self-eating' of the damaged and misfolded proteins and nucleic acids, damaged mitochondria, and other impaired organelles for recycling of cellular building blocks. Autophagy is different from all other cell death mechanisms in one important aspect that it gives the cells an opportunity to survive or demise depending on the circumstances. Autophagy is a therapeutic target for alleviation of pathogenesis in traumatic SCI. However, functions of autophagy in traumatic SCI remain controversial. Spatial and temporal patterns of activation of autophagy after traumatic SCI have been reported to be contradictory. Formation of autophagosomes following therapeutic activation or inhibition of autophagy flux is ambiguous in traumatic SCI studies. Both beneficial and harmful outcomes due to enhancement autophagy have been reported in traumatic SCI studies in preclinical models. Only further studies will make it clear whether therapeutic activation or inhibition of autophagy is beneficial in overall outcomes in preclinical models of traumatic SCI. Therapeutic enhancement of autophagy flux may digest the damaged components of the central nervous system cells for recycling and thereby facilitating functional recovery. Many studies demonstrated activation of autophagy flux and inhibition of apoptosis for neuroprotective effects in traumatic SCI. Therapeutic induction of autophagy in traumatic SCI promotes axonal regeneration, supporting another beneficial role of autophagy in traumatic SCI. In contrast, some other studies demonstrated that disruption of autophagy flux in traumatic SCI strongly correlated with neuronal death at remote location and impaired functional recovery. This article describes our current understanding of roles of autophagy in acute and chronic traumatic SCI, crosstalk between autophagy and apoptosis, therapeutic activation or inhibition of autophagy for promoting functional recovery, and future of autophagy in traumatic SCI. | Swapan K.Ray | 2020 | Neural Regeneration Research2020，15，9： | 9 |
| 7 | Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons显示文摘Objective:An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury,and that regulating autophagy can enhance recovery from spinal cord injury.However,the effect of regulating autophagy and whether autophagy is detrimental or beneficial after spinal cord injury remain unclear.Therefore,in this study we evaluated the effects of autophagy regulation on spinal cord injury in rats by direct and indirect comparison,in an effort to provide a basis for further research.Data source:Relevant literature published from inception to February 1,2018 were included by searching Wanfang,CNKI,Web of Science,MEDLINE(OvidSP),PubMed and Google Scholar in English and Chinese.The keywords included'autophagy','spinal cord injury',and'rat'.Data selection:The literature included in vivo experimental studies on autophagy regulation in the treatment of spinal cord injury(including intervention pre-and post-spinal cord injury).Meta-analyses were conducted at different time points to compare the therapeutic effects of promoting or inhibiting autophagy,and subgroup analyses were also conducted.Outcome measure:Basso,Beattie,and Bresnahan scores.Results:Of the 622 studies,33 studies of median quality were included in the analyses.Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=1.80,95%CI:0.81-2.79,P=0.0004),3 days(MD=0.92,95%CI:0.72-1.13,P<0.00001),1 week(MD=2.39,95%CI:1.85-2.92,P<0.00001),2 weeks(MD=3.26,95%CI:2.40-4.13,P<0.00001),3 weeks(MD=3.13,95%CI:2.51-3.75,P<0.00001)and 4 weeks(MD=3.18,95%CI:2.43-3.92,P<0.00001)after spinal cord injury with upregulation of autophagy compared with the control group(drug solvent control,such as saline group).Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=6.48,95%CI:5.83-7.13,P<0.00001),2 weeks(MD=2.43,95%CI:0.79-4.07,P=0.004),3 weeks(MD=2.96,95%CI:0.09-5.84,P=0.04)and 4 weeks(MD=4.41,95%CI:1.08-7.75,P=0.01)after spinal cord injury with downregulation of autophagy compared with the control group.Indirect comparison of upregulation and downregulation of autophagy showed no differences in Basso,Beattie,and Bresnahan scores at 1 day(MD=-4.68,95%CI:-5.840 to-3.496,P=0.94644),3 days(MD=-0.28,95%CI:-2.231-1.671,P=0.99448),1 week(MD=1.83,95%CI:0.0076-3.584,P=0.94588),2 weeks(MD=0.81,95%CI:-0.850-2.470,P=0.93055),3 weeks(MD=0.17,95%Cl:-2.771-3.111,P=0.99546)or 4 weeks(MD=-1.23,95%Cl:-4.647-2.187,P=0.98264)compared with the control group.Conclusion:Regulation of autophagy improves neurological function,whether it is upregulated or downregulated.There was no difference between upregulation and downregulation of autophagy in the treatment of spinal cord injury.The variability in results among the studies may be associated with differences in research methods,the lack of clearly defined autophagy characteristics after spinal cord injury,and the limited autophagy monitoring techniques.Thus,methods should be standardized,and the dynamic regulation of autophagy should be examined in future studies. | Duo Zhang Di Zhu Fang Wang Ji-Chao Zhu Xu Zhai Yuan Yuan Chen-Xi Li | 2020 | Neural Regeneration Research2020，15，6： | 5 |
| 8 | Duration-dependent regulation of autophagy by isoflurane exposure in aged rats显示文摘Current evidence suggests a central role for autophagy in many inflammatory brain disorders, including Alzheimer's disease(AD). Furthermore, it is also well accepted that some inhalation anesthetics, such as isoflurane, may cause ADlike neuropathogenesis and resultant postoperative cognitive dysfunction, especially in the elderly population. However, the impact of inhalation anesthetics on autophagic components in the brain remains to be documented. Hence, our objective was to investigate the effects of different durations of isoflurane exposure on hippocampus-dependent learning and hippocampal autophagy in aged rats. Aged Sprague-Dawley rats(20 months old) were randomly exposed to 1.5% isoflurane or 100% oxygen for 1 or 4 h. Animals were then trained in the Morris water maze(4 trials/day for 5 consecutive days). Hippocampal phagophore formation markers, beclin 1 and protein microtubule-associated protein 1 light chain-3B(LC3B), as well as p62, an indicator of autophagic flux, were quantified by western blotting. There was no significant difference in the escape latencies and time spent in the target quadrant, as well as hippocampal expression of beclin 1, LC3 BII, and p62 at 24 h post-anesthesia between the1-h isoflurane-exposed rats and their controls(P >0.05). Four-hour exposure to isoflurane resulted in spatial learning and memory deficits, as evidenced by prolonged escape latencies on days 4 and 5 postanesthesia and less time spent in the target quadrant than sham-exposed animals(P <0.05). These events were accompanied by a decline in hippocampal expression of LC3B-I, LC3B-II, and beclin 1 24 h after isoflurane(P <0.01 and P <0.05). Nevertheless, no significant change in p62 expression was found. Further kinetics study of autophagic changes induced by 4 h of isoflurane showed a transient upregulation of LC3B-I, LC3B-II, and beclin 1 at the end of exposure and a subsequent striking decrease w ithin 12–24 h post-anesthesia(P <0.05). Hippocampal p62 p eaked at 6 h but subsequently resolved. These results from our pilot in vivo study support a durationdependent relationship between 1.5% isoflurane exposure, and s patial cognitive function as well as hippocampal phagophore formation. | Zheng-Qian Li Lun-Xu Li Na Mo Yi-Yun Cao Bolati Kuerban Yao-Xian Liang Dong-Sheng Fan De-Hua Chui Xiang-Yang Guo | 2015 | Neuroscience Bulletin2015，31，4： | 5 |
| 9 | 丙戊酸抑制大鼠创伤性颅脑损伤后炎症反应显示文摘目的研究丙戊酸对大鼠创伤性颅脑损伤后脑水肿、神经功能及炎症反应的影响,以探讨丙戊酸对大鼠创伤性颅脑损伤的保护及机制。方法采用改良FeeneyDM法建立大鼠脑外伤(TBI)模型,将54只雄性成年sD大鼠,体质量220-250g,随机(随机数字法)分为3组(n=18):假手术组(Sham),颅脑损伤(TBI)组,颅脑损伤+丙戊酸处理(TBI+VPA)组。其中TBI+VPA组大鼠腹腔注射丙戊酸(每次300mg/kg,12h/次),分别于伤后1、3、7d进行神经行为学评分(mNSS),断颈处死,取骨窗边缘2mm处挫伤脑皮质采用干湿质量法测损伤区脑水含量;免疫荧光测定脑组织中巨噬细胞侵润情况;Western blot检查脑组织炎症因子INF-γ、TNF-α、IL-6表达水平的变化。统计分析采用SPSS13.0进行成组资料方差分析和X2检验。结果与Sham组比较,其余2组脑水含量和神经功能损伤评分升高,脑组织巨噬细胞侵润,炎症因子INF-γ、TNF-α、IL-6表达上调(均P〈0.05);与TBI组比较,TBI+VPA组大鼠创伤后脑水含量明显降低[3d:(80.12±0.59)% vs.(82.14±0.67)%,P=0.04;7d:(74.74±0.72)%绑.(77.93±0.48)%,P=0.01];神经功能评分也相应改善[3d:(10.53±0.32) vs.(11.74±0.48),P=0.02;7d:(7.97±0.32) vs.(10.73±0.42),P=0.01];TBI+VPA组挫裂伤脑组织中巨噬细胞阳性率低于TBI组[(25.93±0.48)% vs.(36.44±0.72)%,P=0.00],脑组织中炎症因子INF-γ、TNF-α、IL-6表达也明显降低(P〈0.05)。结论丙戊酸对大鼠创伤性颅脑损伤具有神经保护作用,其机制可能是通过抑制伤后脑组织中巨噬细胞侵润,降低炎症因子INF-γ、TNF-α、IL-6表达,减轻伤后继发的炎症反应。 | 魏冠 林清江 陈炳基 孙文栋 黄晓磊 陈祥荣 陈峻严 | 2017 | 中华急诊医学杂志2017，26，3： | 4 |
| 10 | 丙戊酸对大鼠创伤性颅脑损伤后脑水肿和神经功能的影响显示文摘目的 观察丙戊酸对大鼠创伤性颅脑损伤后脑水肿的影响及磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路在其中的作用.方法 采用Feeney法建立大鼠创伤性脑损伤模型.72只健康雄性成年SD大鼠,采用随机数字表法分为4组(n=18):假手术组(Sham组)、创伤性颅脑损伤组(TBI组)、TBI+丙戊酸处理组(TBI+ VPA组)和TBI+ PI3K特异性抑制剂LY29400组(TBI+ LY组).分别于伤后1、3、7d进行神经行为学评分(mNSS);采用干湿重法测损伤区脑组织脑水含量;免疫荧光染色测定脑组织中组蛋白去乙酰化酶1(HDAC1)、基质金属蛋白酶-9(MMP-9)蛋白表达;Westerrn blot检查脑组织HDAC1、MMP-9和PI3K/Akt信号通路相关蛋白(PI3K、p-PI3K、Akt和p-Akt)表达水平的变化.结果 建模后第1、3、7天,与Sham组比较,TBI、TBI+ VPA、TBI+ LY组的mNSS评分显著升高,脑水含量显著增高;TBI、TBI+ VPA、TBI+ LY组脑组织HDAC1、MMP-9和PI3K/Akt通路相关蛋白表达均显著上调(P<0.01).模型建立后第3、7天,与TBI组比较,TBI+ VPA组和TBI+ LY组的mNSS评分显著低于TBI(TBI+ VPA组:10.83±0.48比12.04 ±0.51、P<0.05,8.55±0.29比10.73±0.42、P<0.05;TBI+ LY组:10.24±0.38比12.04±0.51,P<0.05,7.83±0.26比10.73±0.42,P<0.01);脑组织含水量显著降低[TBI+VPA组:(80.01±0.61)%比(82.87±0.69)%,P <0.05,(75.88±0.52)%比(78.33±0.41)%,P <0.05;TBI+ LY组:(79.59±0.57)%比(82.87±0.69)%,P<0.05,(74.94±0.43)%比(78.33±0.41)%,P<0.01].模型建立后第3天,与TBI组比较,TBI+ VPA组和TBI+ LY组脑组织HDAC1和MMP-9蛋白,PI3K/Akt通路中p-PI3K和p-Akt表达下调(P<0.05).结论 丙戊酸可减轻大鼠创伤性脑损伤后脑水肿,改善伤后神经功能,其机制可能与抑制脑组织PI3K/Akt信号通路活化,降低MMP-9的表达相关. | 陈祥荣 李亚松 骆良钦 胡伟鹏 庄丽明 | 2016 | 中华实验外科杂志2016，33，11： | 4 |
| 11 | 脊髓损伤中的自噬及相关研究进展显示文摘脊髓损伤(spinal cord injury,SCI)是一种严重的神经系统创伤,会导致损伤节段以下肢体功能障碍,不仅给患者本人带来身体和心理的严重伤害,还会给社会带来巨大的经济负担。SCI的常见病因有高处坠落伤、交通事故、重物砸伤、运动损伤等。进入20世纪后半叶,随着我国经济水平的快速发展,SCI的发生率呈现逐年升高趋势,上海市1991年统计的SCI发生率为34.4人/百万人,北京市2002年SCI的发生率为60人/百万人,粗略估计我国每年大约有1万人发生SCI。然而面对这种发生率逐年升高的高致残性疾病,迄今为止仍没有有效的治疗方法。目前对SCI的机制研究已成为脊柱外科和神经学科等领域的热点和难点,其中自噬被认为在SCI中对脊髓的保护起重要作用。虽然对SCI中自噬机制的研究已经取得进展,但仍存在一些争议点:(1)不同SCI模型中自噬的变化过程在各研究中并不一致;(2)不同药物和试剂对不同SCI模型中自噬的影响和对受损脊髓的治疗效果还不明确。笔者就自噬的相关内容、SCI中自噬和凋亡的关系、不同SCI模型中自噬的变化过程、不同药物和试剂对SCI模型中自噬的影响和对受损脊髓的治疗效果进行综述,以期为SCI患者减轻损伤、提高生活质量提供新思路。 | 徐伟龙 赵岩 | 2019 | 中国脊柱脊髓杂志2019，29，4： | 4 |
| 12 | 脊髓损伤中自噬的研究进展显示文摘脊髓损伤(spinal cord injury,SCI)是常见的中枢神经系统疾病之一,在直接或间接损伤的作用下,脊髓功能障碍导致了损伤部位以下的感觉、运动及其他功能丧失。美国国家SCI统计中心统计,美国约有28.8万人患有SCI,每年新增SCI病例17000例,其对患者身心及社会经济造成了巨大损害[1]。根据其病理生理机制,SCI可分为两个阶段:原发性和继发性损伤[2]。原发性损伤包括直接的机械损伤及其造成的轴突、细胞膜及血管损伤。 | 刘方煜 范一鸣 张洪宇 李帅 王岩松 | 2021 | 中国脊柱脊髓杂志2021，31，4： | 3 |
| 13 | 醒脑静注射液对大鼠颅脑损伤氧化应激的影响显示文摘目的:评价不同浓度醒脑静注射液对大鼠创伤性脑损伤(Traumatic Brain Injury,TBI)氧化应激损伤的影响。方法:选择普通级雄性Wistar大鼠216只,随机分为空白对照组、假手术组、TBI模型组、醒脑静低剂量组、醒脑静中剂量组及醒脑静高剂量组,每组36只。采用Feeney’s自由落体方法制作大鼠外伤性脑损伤模型,假手术组仅进行颅骨转开,空白组不做任何处理;假手术组、空白对照组与TBI模型组在模型构建成功后0.9%氯化钠溶液注射5 mL/(kg·d),低剂量组、中剂量组及高剂量组分别注射0.5 mg/(kg·d)、1 mg/(kg·d)及2 mg/(kg·d)的醒脑静注射液。分为1 h、3 d及7 d于各组随机选取8只大鼠取血、处死并取脑组织。检测脑组织中丙二醛(MDA)及超氧化物歧化酶(Super Oxide Dismutase,SOD)水平,检测血液样本中超敏C-反应蛋白(High-sensitivity C-reactive Protein,hs-CRP)与肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)水平,检测各组大鼠脑组织神经元细胞凋亡指数。结果:(1)TBI模型构建后,大鼠脑组织中MDA在术后3 d达到最高,SOD水平术后3 d降到最低。术后3 d及7 d MDA与TBI模型组比较,醒脑静治疗组MDA水平随醒脑静用量上升而降低,中、高剂量组显著低于TBI模型组与低剂量组(P<0.05),但中、高剂量组间无统计学差异(P>0.05);SOD与TBI模型组比较,醒脑静治疗组水平随醒脑静用量上升而升高,中高剂量组间差异无统计学意义(P>0.05)。(2)血清hs-CRP及TNF-α在造模后显著升高,在造模后3 d最高,与TBI模型组比较,醒脑静治疗组随醒脑静用量上升呈降低趋势,中剂量组与高剂量组间无统计学差异(P>0.05)。(3)细胞凋亡检测结果,造模后3 d脑细胞凋亡率最高,造模3 d与7 d脑细胞凋亡率TBI模型组最高,空白对照组最低;醒脑静治疗组脑细胞凋亡率随醒脑静剂量上升降低,中剂量组与高剂量组显著低于TBI模型组与低剂量组(P<0.05),但中剂量组与高剂量组无统计学差异(P>0.05)。结论:(1)醒脑静注射液可有效减少大鼠模型构建后氧化应激损伤及炎症反应,减少中枢神经元细胞凋亡;(2)醒脑静注射液对TBI大鼠模型的保护效应存在剂量依赖性,中剂量组[(1 mg/(kg·d)]即可达到较为明确的保护效应。 | 周正山 贾军生 桑昭熙 袁野 王海涛 张好臣 | 2021 | 中医临床研究2021，13，7： | 2 |
| 14 | 自噬在脊髓细胞中的作用与机制研究进展显示文摘脊髓损伤(spinal cord injury,SCI)是脊柱外科常见的复杂神经系统疾病,尽管不同脊髓损伤存在病理生理差异,但在许多方面损伤机制相似。损伤引起的一系列生化变化为继发性损伤,存在自噬迹象,但自噬的机制仍不清楚。综述了脊髓损伤后自噬在不同类型细胞中作用机制的研究进展及自噬对受损组织的影响。 | 朱宁 杨新明 张瑛 | 2020 | 河北北方学院学报(自然科学版)2020，36，6： | 2 |
| 15 | 硫化氢对大鼠急性脊髓损伤的保护作用显示文摘目的探讨硫化氢(H2S)对大鼠急性脊髓损伤后自噬及细胞凋亡的影响。方法 36只健康雄性SD大鼠随机分为假手术组(Sham组)、单纯脊髓损伤组(模型组)、H2S处理组(H2S组),每组12只。采用Allen’s法构建大鼠脊髓损伤模型,Sham组只行椎板切除术,暴露脊髓不打击;H2S组在脊髓损伤后1 h腹腔注射50μmol/kg硫氢化钠;模型组给予等体积生理盐水。各组脊髓损伤24 h后取出脊髓组织,Western blot检测LC3、p70S6K和Cleaved cas-pase-3表达;免疫荧光法检测LC3表达;TUNEL染色法检测各组细胞凋亡率。结果与Sham组相比,模型组LC3Ⅱ/LC3Ⅰ,Cleaved caspase-3表达升高,p70S6K表达降低、细胞凋亡率升高(P<0.01);与模型组相比,H2S组LC3Ⅱ/LC3Ⅰ、Cleaved caspase-3表达降低,p70S6K表达升高,细胞凋亡率下降(P<0.01)。结论 H2S可抑制大鼠急性脊髓损伤后自噬并减少细胞凋亡。 | 孙平 范仲凯 李昊天 王继权 赵兴长 李刚 吕刚 | 2015 | 天津医药2015，43，11： | 2 |
| 16 | 丙戊酸钠联合甲强龙对大鼠脊髓损伤的影响及其机制显示文摘目的探讨丙戊酸钠(VAP)联合甲强龙(MP)在大鼠脊髓损伤(SCI)后神经功能恢复中的作用及其机制。方法选取8~10周龄雄性健康SD大鼠60只,按照数字表法随机分为假手术组、SCI组、VAP组、MP组和VAP+MP组,每组12只;各组大鼠再按照数字表法随机分为A组、B组2个亚组,每组6只。假手术组仅暴露脊髓、不做SCI处理,其余4组均采用改良Allen法进行大鼠SCI模型制备。假手术组、SCI组术后30 min、6 h、8 h和24 h腹腔注入生理盐水(剂量为30 mg/kg),24 h后每天腹腔注入相同剂量生理盐水,持续28 d;VAP组:分别于术后于30 min、6 h和24 h腹腔注入生理盐水(30 mg/kg),术后8 h腹腔注入VAP(30 mg/kg),24 h后每天腹腔注入相同剂量VAP,持续28 d;MP组:分别于术后30 min、6 h和24 h腹腔注入MP(30 mg/kg),术后8 h腹腔注入生理盐水(30 mg/kg),24 h后每天腹腔注入相同剂量生理盐水,持续28 d;VAP+MP组:分别于术后30 min、6 h和24 h腹腔注入MP(30 mg/kg),术后8 h腹腔注入VAP(30 mg/kg),24 h后每天腹腔注入相同剂量VAP,持续28 d。选取各组A亚组大鼠:术后第1、3、7、14、28天,分别采用脊髓损伤行为学运动功能(BBB)评分标准和改良Rivlin斜板试验评价SCI后各组大鼠肢体运动功能的恢复情况。选取各组B亚组大鼠:术后第7天手术切取SCI区域脊髓组织,HE染色观察各组大鼠脊髓组织形态变化,Nissl染色观察脊髓运动神经元情况并计算凋亡运动神经元数目,免疫组织化学染色半定量分析肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)蛋白的相对表达情况,Western blot法检测凋亡相关蛋白B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关的X因子(Bax)、caspase-3的相对表达情况。结果(1)组内比较:与术前相比,假手术组术后第1、3、7、14、28天BBB评分和Rivlin斜板试验结果差异均无统计学意义(P值均>0.05);SCI组、VAP组、MP组、VAP+MP组术后不同时间点BBB评分和Rivlin斜板试验结果均明显降低,但随着时间延长,BBB评分和Rivlin斜板试验结果逐渐升高,差异均有统计学意义(P值均<0.05)。组间比较:SCI组、VAP组、MP组、VAP+MP组SCI后BBB评分和Rivlin斜板试验结果均显著低于假手术组,VAP组、MP组、VAP+MP组的BBB评分和Rivlin斜板试验结果均高于SCI组,VAP+MP组BBB评分和Rivlin斜板试验结果均高于VAP组、MP组,差异均有统计学意义(P值均<0.05)。(2)假手术及造模后第7天,HE染色观察组织学特征:假手术组脊髓组织形态正常;SCI组脊髓组织可见脊髓灰质出现大量炎性细胞因子浸润,细胞出血、水肿,运动神经元坏死、凋亡明显;VAP组、MP组、VAP+MP组较SCI组大鼠脊髓组织可见出血水肿显著减轻,炎性细胞因子浸润显著减少,运动神经元溶解、凋亡减轻,其中VAP+MP组效果更加显著。SCI组、VAP组、MP组、VAP+MP组脊髓空洞面积均明显大于假手术组,VAP组、MP组、VAP+MP组脊髓空洞面积均明显小于SCI组,VAP+MP组脊髓空洞面积均小于VAP组和MP组,差异均有统计学意义(P值均<0.05)。(3)假手术及造模后第7天,Nissl染色观察脊髓运动神经元数目:SCI组、VAP组、MP组、VAP+MP组大鼠脊髓组织正常运动神经元数目明显少于假手术组,VAP组、MP组、VAP+MP组正常运动神经元数目均高于SCI组,VAP+MP组正常运动神经元数目均高于VAP组、MP组,差异均有统计学意义(P值均<0.05)。(4)假手术及造模后第7天,免疫组织化学检测TNF-α、IL-1β表达情况:SCI组、VAP组、MP组、VAP+M组TNF-α、IL-1β表达明显高于假手术组,VAP组、MP组、VAP+MP组TNF-α、IL-1β表达水平显著低于SCI组,VAP+MP组TNF-α、IL-1β表达明显低于VAP组和MP组,差异均有统计学意义(P值均<0.05)。(5)假手术及造模后第7天,Western blot法测试大鼠脊髓组织中凋亡蛋白表达情况:与假手术组比较,SCI组、VAP组、MP组、VAP+MP组凋亡相关蛋白Bcl-2、Bax和caspase-3的相对表达量明显增加;与SCI组比较,VAP组、MP组、VAP+MP组Bcl-2的相对表达量明显增加,Bax、caspase-3的相对表达量明显减少;VAP+MP组Bcl-2的相对表达量明显高于VAP组、MP组,Bax、caspase-3的相对表达量明显低于VAP组、MP组:差异均有统计学意义(P值均<0.05)。结论VAP联合MP能够显著改善大鼠SCI后神经运动功能,其机制可能与抑制局部炎性反应、促进抗凋亡蛋白Bcl-2的表达和减少凋亡蛋白Bax、caspase-3的表达有关。 | 孙建威 杨新明 张瑛 | 2021 | 中华解剖与临床杂志2021，26，2： | 2 |
| 17 | 抑制自噬减少大鼠脊髓损伤后髓鞘碱性蛋白的丢失显示文摘目的:观察自噬抑制剂对脊髓损伤后髓鞘碱性蛋白(MBP)表达的影响。方法:将99只大鼠随机分成假手术组、损伤组和干预组各33只,各组再分成损伤后3、7、14 d 3个时间点,应用打击器制备T10脊髓损伤模型。干预组造模前注射1μL 3-甲基腺嘌呤(3-MA)。假手术组不造成打击。提取脊髓样本进行Western blot和实时定量荧光PCR检测自噬相关蛋白LC3-Ⅱ和MBP的蛋白、m RNA水平。用BBB行为学评分分别于伤后1、7、14 d评估大鼠。结果:伤后14 d时干预组的BBB评分明显高于损伤组(P=0.001)。损伤组各时间点大鼠脊髓损伤区域的LC3-Ⅱ蛋白含量较假手术组明显增加(P<0.05),干预组损伤区域的LC3-Ⅱm RNA和蛋白水平在伤后3、7、14 d均比损伤组减少(P<0.05)。干预组大鼠损伤区域的MBP m RNA和蛋白水平在伤后3、7、14 d均比损伤组增加(P<0.05)。结论:大鼠脊髓损伤后存在自噬的过度激活,自噬抑制剂可通过减少脊髓损伤后MBP的丢失发挥神经保护作用。 | 杨德刚 李建军 杨明亮 杜良杰 褚宏宇 胡安明 高峰 李军 顾蕊 | 2015 | 神经损伤与功能重建2015，10，3： | 1 |
| 18 | NGAL及自噬在大鼠肾脏缺血/再灌注损伤中的表达及意义显示文摘目的明确大鼠肾脏缺血/再灌注(ischemia/reperfusion,I/R)损伤后不同时间中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)表达水平及肾组织自噬状态的变化情况及意义。方法建立大鼠肾脏I/R损伤模型,将30只Wistar雄性大鼠按随机数字表法分为假手术组(Sham组)和I/R组,按照再灌注时间,将I/R组分为2h组、6h组、24h组和48h组。在上述不同时间点分别留取大鼠血、尿及肾组织标本。采用酶联免疫吸附试验(enzyme-linked immunoadsordent assay,ELISA)检测血和尿中NGAL水平;全自动生化分析仪检测血尿素氮(blood urea nitrogen,BU)和血肌酐(serum creatinine,SCr)水平;苏木精-伊红染色法检测肾组织损伤程度并进行损伤程度积分;应用原位末端标记法(TdT-mediated dUTP nick end labeling,TUNEL)法检测肾小管上皮细胞凋亡情况;实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测自噬相关基因LC3及Beclin-1的表达。结果血和尿中NGAL表达水平在I/R损伤后2h即开始升高,6h达到高峰,24h后呈下降趋势。BU及Scr在I/R损伤后6h开始升高,24h达到高峰。TUNEL阳性细胞于I/R损伤后6h开始增加,24h数量达峰值。苏木精-伊红染色显示,I/R损伤后各组均有不同程度的肾小管上皮细胞肿胀、坏死。从I/R损伤后6h开始,LC3和Beclin-1基因表达呈上升趋势,24h后LC3和Beclin-1基因表达量达高峰。结论大鼠肾脏I/R损伤早期NGAL表达水平即升高,早于BU、SCr水平的变化,可以作为早期诊断肾脏I/R损伤的分子指标。大鼠肾脏I/R损伤加重过程中NGAL表达呈增加趋势,自噬被激活,提示NGAL蛋白及自噬均在I/R损伤过程中发挥一定的作用。 | 张雅丽 张敏 邢晓英 孙萌萌 齐冉 乔淑凯 | 2023 | 医学研究杂志2023，52，11： | 0 |
| 19 | An update on spinal cord injury research显示文摘Spinal cord injury (SCI) is an ever-increasing challenge. Severe injury can cause long-term loss of sensory and motor functions, as well as other chronic conditions, such as neuropathic pain and autonomic dysreflexia. So far, most research has been focused on acute injury. However, due to the lack of treatment, | Yimin Zou | 2013 | Neuroscience Bulletin2013，29，4： | 0 |
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