小剂量多巴胺对大鼠颅脑创伤后水通道蛋白4表达的影响

目的观察小剂量多巴胺对大鼠颅脑创伤后水通道蛋白4（AQP4）表达的影响。方法49只成年雄性wistar大鼠,随机分为对照组（7只）、创伤组（21只）及多巴胺干预组（21只）,多巴胺干预组小剂量多巴胺5μg（kg·min）持续给药．创伤组给予等量的生理盐水,对照组不予处理。分别予伤后0．5h、2h、6h、12h、24h、48h、72h断头取脑．采用半定量反转录聚合酶链反应（RT—PCR）检;刚脑组织AQP。1mRNA表达及其变化规律。结果创伤组脑组织AQP4mRNA在伤后0．5h开始表迭上调,2h、6h、12h依次增高,24h达到峰值后回落。多巴胺干预组AQP4mRNA在伤后0．5h表达上调,12h达到峰值,后逐渐回落。与创伤组相比,多巴胺干预组在相应时间点AQP4tuRNA表达减少（P〈0．05）,并使AQP4mRNA峰值提前。结论小剂量多匕胺可以减少AQP4mRNA在大鼠颅脑创伤后的表达,减轻创伤后脑水肿．加快脑水肿的恢复,具有脑保护作用。     

水通道蛋白-4与脑水肿

通道蛋白-4（AQP4）是水通道蛋白家族的一个亚型。大量的研究表明脑水肿后AQP4表达明显增强，提示AQP4可能参与了脑水肿的发生、发展过程，在脑水肿的形成过程中起重要作用。抑制AQP4的表达可能是防治脑水肿的一种有效途径。     

水通道蛋白-4与脑水肿

脑水肿是一种临床常见的病理生理学反应.目前认为,水通道蛋白-4(AQP4)参与了脑水肿的形成和消退,其结构、分布和表达调控的最新研究成果均提示,AQP4在脑水肿中起着重要作用.     

水通道蛋白-4与脑水肿

根据发生机制,脑水肿可分为细胞毒性水肿和血管源性水肿。前者是细胞膜正常渗透梯度被破坏导致水渗透性内流进入细胞,主要为细胞内水肿。血管周围星形胶质细胞足突的水通道蛋白-4(AQP4)可使水通过血脑屏障进入细胞,AQP4基因敲除可显著减少细胞毒性脑水肿模型的液体积聚。相反,血管源性水肿源于一种不依赖AQP的血脑屏障通透性增高机制,导致细胞外液体积聚。研究表明,AQP4有助于消除细胞外液体。基于AQP4与脑水肿形成和消除的关系,AQP和AQP表达调节剂可为脑水肿治疗药物的开发提供新的思路。     

水通道蛋白-4与脑水肿

水通道蛋白(aquaporins,AQP)是一组具有高度选择性的水通道蛋白家族.AQP4在脑内星形胶质细胞中含量最高,是中枢神经系统中最主要的水通道蛋白,参与了脑血管病、脑挫伤、肿瘤、炎症等引起的脑水肿的一系列病理学过程.AQP4在脑缺血后水肿形成中的作用机制仍存在争议.选择性调节AQP4的表达,干预其作用环节,将为临床脑缺血后水肿的治疗提供新的思路和手段.     

水通道蛋白-4与脑水肿

脑水肿是一种临床常见的病理生理学反应。目前认为，水通道蛋白-4（AQP4）参与了脑水肿的形成和消退，其结构、分布和表达调控的最新研究成果均提示，AQP4在脑水肿中起着重要作用。     

二甲双胍对老龄大鼠脑缺血再灌注损伤脑水肿的影响

目的 探讨二甲双胍对老龄大鼠脑缺血再灌注损伤(CIR)脑水肿的影响及机制。方法 选择健康老龄SD大鼠随机分为假手术组(n=20)、缺血/再灌注(I/R)组(n=20)、二甲双胍组(n=20),后两组通过线栓法建立CIR模型,二甲双胍组给予二甲双胍(50 mg/kg)腹腔注射,I/R组给予等量的0.9%生理盐水腹腔注射,连续7 d, 7 d后检测脑血流量、脑组织含水量及神经功能缺损情况,苏木素-伊红(HE)观察脑组织病理变化,检测脑组织一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)变化。RT-PCR、Western印迹检测脑组织基质金属蛋白酶(MMP)-2、MMP-9、水通道蛋白(AQP)9表达。结果 与假手术组相比,I/R组脑组织含水百分数、NO、MDA含量、神经功能缺损评分、脑组织MMP-2、MMP-9、AQP9表达均显著升高(P<0.05),脑血流量及脑组织SOD、CAT、GSH-Px活性显著降低(P<0.05);与I/R组相比,二甲双胍组脑组织含水百分数、NO、MDA含量、神经功能缺损评分、脑组织...     

急性肝衰竭大鼠脑水通道蛋白-4表达与脑水肿关系研究

急性肝功能衰竭（ALF）脑水肿常是导致死亡的直接原因和预后决定因素。ALF脑水肿是以星形胶质细胞肿胀为特征性的细胞性水肿。水通道蛋白-4（AQP-4）特异表达在星形胶质细胞膜，感受细胞内外渗透压的变化，调节水的跨细胞膜流动是细胞肿胀的分子基础。磁共振扩散加权成像（DWI）对细胞内、外水分子的扩散运动较敏感，能发现活体组织中水分布变化。通过建立大鼠ALF模型检测MR信号、血氨水平和AQP-4表达，探讨AQP-4在ALF脑水肿中的生化和分子机制。     

水通道蛋白-4与脑水肿的相关性研究进展

水通道蛋白4(AQP4)是一种高度表达于细胞膜且能够允许水分子跨膜转运的膜蛋白,主要位于脑内星形胶质细胞、软脑膜、室管膜上皮细胞等与水平衡密切相关的部位。AQP4的这种分布特征说明对水分子出入脑组织具有一定的调节作用,在各种脑水肿的发生发展中起重要作用。对AQP4的结构、分布、功能、调控机制及与脑水肿的关系进行综述。     

肝硬化大鼠脑水通道蛋白-4、胶质纤维酸性蛋白表达与脑水肿关系

目的观察肝硬化大鼠脑组织中AQP-4和GFAP的表达并探讨其和脑水肿发生的关系.方法硫代乙酰胺法建立肝硬化大鼠模型;脑MR DWI扫描,测定DWI、ADC值;检测动脉血氨水平;免疫组化图像分析脑组织中AQP-4、GFAP表达水平:观察大脑星形胶质细胞形态、血脑屏障超微结构变化.结果成功建立肝硬化大鼠模型;对照组MRI DWI扫描在感兴趣区域信号无差异(P＞0.05);肝硬化组和对照组间动脉血氨水平无差异(P＞0.05);肝硬化组大鼠脑组织中AQP-4、GFAP表达增高(P＜0.05).病理观察发现血管周围间隙增加,电镜下见轻微脑星形胶质细胞水肿,血脑屏障无改变.结论肝硬化大鼠脑组织中AQP-4、GFAP表达上调并伴有隐性的细胞水肿,GFAP表达增加和正常的血氨水平可能减轻AQP-4对脑水肿发生的影响.     

牛磺酸对重度颅脑创伤大鼠脑组织AQP4/牛磺酸转运体基因的影响

目的研究牛磺酸（Tau）对重度颅脑创伤（TBI）大鼠脑组织的脑组织含水量、水通道蛋白-4（AQP-4）/Tau转运体（TAUT）基因表达的影响。方法按随机数字表法将84只雄性SD大鼠分为7组：假手术组（Sham组）、脑外伤组（TBI组）、Tau治疗组（Tau组）,Tau预防组（Pre-Tau组）、β-丙氨酸组（β-Ala组）、维生素C组（Vc组）、叶酸组（Fa组）,每组12只。后6组均采用液压打击制作重度TBI模型。造模成功后即刻尾静脉给药200 mg/kg。Sham组和TBI组给予相同量等渗盐水,24 h后取脑。采用HE染色法观察TBI后各组脑组织形态学变化、测定脑组织含水量,用荧光定量RT-PCR方法检测AQP-4/TAUT基因表达。结果形态学检查：TBI 24 h后,神经细胞肿胀,细胞丢失,细胞核固缩,突起短小消失,坏死灶边缘可见炎性细胞浸润,β-Ala组同TBI组。但与TBI组比较,Tau组、Vc组、Fa组、Pre-Tau组形态上无显著改善;脑组织含水量：与Sham组相比,TBI组、β-Ala组伤后24 h显著升高（P〈0.05）。而Tau组、Vc组、Fa组明显降低,与Sham组无统计学差异;Pre-Tau组显著低于Sham组（P〈0.05）。基因表达：与Sham组相比,TBI组脑组织AQP-4 mRNA表达量显著升高（P〈0.05）,Fa组TAUT mRNA表达量显著升高（P〈0.05）。结论 Tau、Vc、Fa及Tau预防性治疗均可以显著降低脑水肿和AQP-4基因表达,对TBI后脑水肿有较好的治疗作用,但Tau、Vc对TBI早期的TAUT无调节作用,其对脑组织含水量的有效性并不是通过调节TAUT实现的。     

腹泻型肠易激综合征患者结肠黏膜AQP4、AQP8相关性表达

目的检测正常人、腹泻型肠易激综合征(IBS)患者升、降结肠黏膜水通道蛋白(AQP)4与AQP8的表达情况,探讨AQP4、AQP8的表达与腹泻型IBS的相关性。方法采用荧光定量逆转录聚合酶链反应(FQ-RT-PCR)方法。结果AQP4在正常人、腹泻型IBS患者升结肠和降结肠所有标本的荧光生长曲线呈阴性,而AQP8的荧光生长曲线呈阳性。正常人和腹泻型IBS患者升结肠组织黏膜AQP8mRNA表达均显著高于降结肠(P=0.032,P=0.028);且无论在升结肠还是降结肠组织黏膜,腹泻型IBS患者AQP8 mNRA表达均显著低于正常人(P=0.030,P=0.012)。结论人体结肠组织中AQP4极少表达或无表达。生理状态下AQP8可能与结肠水吸收相关,腹泻型IBS的发生可能与AQP8的表达减少有一定相关性。     

三七总皂甙对脑出血后大鼠脑水肿及水通道蛋白-4表达的影响

目的观察三七总皂甙对脑出血大鼠脑水肿形成及水通道蛋白-4(AQP4)表达的影响。方法Wistar大鼠198只随机分为A、B、C 3个部分,分别检测脑含水量、AQP4蛋白和AQP4 mRNA,每部分又随机分为假手术组,模型组,治疗组,采用干湿重法、免疫组织化学染色、逆转录聚合酶链反应技术分别测定脑含水量、AQP4蛋白和AQP4 mRNA的表达。结果治疗组和模型组12 h之后脑含水量增加(P<0.05),1天时脑含水量明显增加(P<0.01),3天时脑含水量达到高峰并持续到5天,在相同的时间点,治疗组脑含水量比模型组明显少(P<0.05);模型组和治疗组12 h之后AQP4蛋白和AQP4 mRNA表达水平增加(P<0.05),1天时明显升高(P<0.01),3天达到高峰持续至5天,以后逐渐下降,与模型组比较,治疗组大鼠在各时间点AQP4蛋白、AQP4 mRNA均在低水平表达(P<0.05),1-5天表达水平明显下降(P<0.01)。结论三七总皂甙可能通过抑制AQP4的表达减轻脑出血后脑水肿的形成。     

Assessment of traumatic brain injury degree in animal model

Objective:To establish stable and controllable brain injury with accurate degree and good repeatability in rat model.Methods:Controlled cortical impact(CCI) device was used to prepare for the rat brain injury model by the impact head of different model(Group A No.4.Group B No.5,Group C No.6) and the impact depth(Group A:1.5-2.0 mm.Group B:2.5-3.0 mm.Group C:3.5-4.0mm) with impact time of 0.1 s and impact velocity of 2.5 m/s.Twelve rats with three months of age were used in each group(the impact depth of every two rats was added 1 mm respectively).After modeling for 1 h,magnetic resonance imaging(MRI) was received and brain histopathology was observed to assess degree of injury by model parameter's of three groups.Results:After modeling of Group A,MRI showed that the cortex structure was damaged with a small amount of bleeding in center and mild edema around,and the total volume of injury was(28.69±4.94)mm~3.Pathology revealed the injury was confined to the superficial cortical with mild edema of nerve cell,which was assessed as mild cerebral contusion.While after modeling,MRI of Group B showed that the structure of cortex and medulla were damaged simultaneously and extended to cerebral nuclei zone,With 4 cases of hematoma in the center and larger edema range around,and the total volume of injury was(78.38±9.28) mm~3.Pathology revealed the injury range was reached nuclei zone,with swell of nerve cell and mitochondria,which was assessed to moderate cerebral contusion.After modeling of Group C,MRI showed that extensive tissue injury was appeared in cortex and medulla and deep nuclei,with 9 cases of hematoma and large edema signal of surrounding tissue T2W1,while in 5 cases,lateral nucleus of injury signal was increased,and the total volume of injury was(135.89±24.80)mm~3.Pathology revealed the deep cerebral nuclei was damaged,with the disappearance of neuronal structure and vacuolization of mitochondria,which was assessed as severe cerebral contusion.MRI changes were consistent with pathological changes in three groups of model,and the injury range was significantly different(P0.01).Conclusions:Application of CCI can make stable quantitative traumatic brain injury model,which overcomes the randomness in previous injury model and possesses highly unity in iconography and pathology changes.This can provide quantitative modeling reference for clinical research.     

Dexamethasone for the treatment of traumatic brain injured patients with brain contusions and pericontusional edema: Study protocol for a prospective,randomized and double blind trial

Background:Traumatic brain injury (TBI) constitutes a leading cause of death and disability. Patients with TBI and cerebral contusions developing pericontusional edema are occasionally given dexamethasone on the belief that this edema is similar to that of tumors, in which the beneficial effect of dexamethasone has been demonstrated.Methods:The DEXCON TBI trial is a multicenter, pragmatic, randomized, triple-blind, placebo controlled trial to quantify the effects of dexamethasone on the prognosis of TBI patients with brain contusions and pericontusional edema. Adult patients who fulfill the elegibility criteria will be randomized to dexamethasone/placebo in a short and descending course: 4 mg/6 h (2 days); 4 mg/8 hours (2 days); 2 mg/6 hours (2 days); 2 mg/8 hours (2 days); 1 mg/8 hours (2 days); 1 mg/12 hours (2 days). The primary outcome is the Glasgow Scale Outcome Extended (GOSE) performed 1 month and 6 months after TBI. Secondary outcomes are: number of episodes of neurological deterioration; symptoms associated with TBI; adverse events; volume of pericontusional edema before and after 12 days of treatment; results of the neuropsychological tests one month and 6 months after TBI. The main analysis will be on an “intention-to-treat” basis. Logistic regression will estimate the effect of dexamethasone/placebo on GOSE at one month and at 6 months, dichotomized in unfavorable outcome (GOSE 1–6) and favorable outcome (GOSE 7–8). Efficacy will also be analyzed using the ''sliding dichotomy’. An interim and safety analysis will be performed including patients recruited during the first year to calculate the conditional power. A study with 600 patients would have 80% power (2 sided alpha = 5%) to detect a 12% absolute increase (from 50% to 62%) in good recovery.Discussion:This is a confirmative trial to elucidate the therapeutic efficacy of dexamethasone in a very specific group of TBI patients: patients with brain contusions and pericontusional edema. This trial could become an important milestone for TBI patients as nowadays there is no effective treatment in this type of patients.Trial Registration:eudraCT: 2019–004038–41; Clinical Trials.gov: {"type":"clinical-trial","attrs":{"text":"NCT04303065","term_id":"NCT04303065"}}NCT04303065.     

Early complementary acupuncture improves the clinical prognosis of traumatic brain edema: A randomized controlled trial

Background:Traumatic brain edema occurs commonly brain injury, and most manifests as pericontusional edema of brain contusions. On the basis of evidence-based medicine, apart from recommending craniotomy and mannitol, there are few particularly effective measures to prevent and treat traumatic brain edema. It is uncertain whether an early complementary acupuncture treatment would improve long-term outcomes of patients with traumatic brain edema. The aim of this study is to assess the efficacy and the safety of early complementary acupuncture for patients with traumatic brain edema.Methods:This study is an actively accruing, single-center, single-blinded, 2-arm, randomized controlled trial. Patients with traumatic brain injury, a Glasgow Coma Scale score of 6∼12, and brain edema on computed tomography scan will be divided into 2 groups on the basis of stratified block randomization. All patients will receive conventional treatment, and the study group will undergo additional acupuncture therapy (start within 72 hours after the injury) once a day for 28 days. The primary outcome is the dichotomized Glasgow Outcome Score at 6 months and 12 months after injury, and the secondary outcomes are the Glasgow Coma Scale, the volume of traumatic brain edema, the serum levels of C-reactive protein and interleukin-6, and the Modified Barthel Index.Discussion:This study will provide data regarding the efficacy of early complementary acupuncture for traumatic brain edema. If the study yields positive results, its findings may offer insights into a valuable complementary option of acupuncture for traumatic brain edema that could provide pilot evidence for large, randomized, controlled trials.Trial registration: This trial has been published in the Chinese Clinical Trial Register, http://www.chictr.org.cn/edit.aspx?pid=141208&htm=4 (Identifier: ChiCTR2100053794, registered on December 3, 2021).