后适应对树鼩不同脑缺血模型同一"时间窗"海马神经元保护的比较

目的: 观察缺血后适应(PC)对血栓性脑缺血(TC)及大脑中动脉闭塞(MCAO)2种脑缺血模型同一"时间窗"的脑保护效果,并探讨其可能机制。方法: 建立树鼩TC及MCAO脑缺血模型,于脑缺血后4 h夹闭同侧颈总动脉实施缺血PC。用TTC染色显示皮层梗塞面积,采用电镜及激光多普勒(LD)技术分别观察脑缺血后4 h、24 h及72 h海马CA1区神经元超微结构及局部脑血流(rCBF)的变化,比较PC对2种中风模型海马 rCBF和神经元超微结构的影响。结果: 脑缺血后海马CA1区神经元的超微结构改变以线粒体肿胀、嵴断裂以及内质网扩张为主,MCAO的梗塞面积和细胞损伤程度明显高于TC组,且PC缓减TC组海马线粒体损伤的作用较MCAO的明显。TC和MCAO后海马rCBF明显降低,TC组rCBF的降低以24 h明显(P＜0.01),而MCAO组rCBF的降低则以72 h明显(P＜0.01)。脑缺血后4 h实施PC可改善TC组海马rCBF(P＜0.01)和减轻线粒体损伤,而MCAO组rCBF及神经元形态学改善不明显。结论: 脑缺血后4 h实施缺血PC能有效对抗缺血性脑损伤,其脑保护效果与rCBF的增加有关。缺血PC对TC组的脑保护作用较MCAO组明显。     

The proteasome inhibitor VELCADE reduces infarction in rat models of focal cerebral ischemia

The potential neuroprotective effects of VELCADE were investigated in two different models of focal cerebral ischemia. For time-window assessment, male Wistar-Kyoto rats were treated with 0.2 mg/kg VELCADE at 1, 2, or 3 h after the induction of permanent middle cerebral artery occlusion (MCAO) using the suture occlusion method (experiment 1). To evaluate effects in a different model, male Sprague-Dawley rats received 0.2 mg/kg VELCADE after embolic MCAO (experiment 2). Infarct volume was calculated based on TTC-staining 24 h postischemia and whole blood proteasome activity was fluorometrically determined in both experiments at baseline, 1 and 24 h post-MCAO. In experiment 1, a dose of 0.2 mg/kg inhibited proteasome activity by 77% and infarct volume was reduced to 175.7+/-59.9 mm3 and 205.9+/-83.9 mm3 (1 and 2 h group, respectively; p<0.05) compared to 306.5+/-48.5 mm3 (control). Treatment at 3 h was not neuroprotective (293.0+/-40.1 mm3). After embolic MCAO, infarct volume was 167.5+/-90.7 mm3 (treatment group) and 398.9+/-141.3 mm3 (control; p=0.002). In conclusion, VELCADE treatment inhibited whole blood proteasome activity and achieved significant neuroprotection in two rat models of focal cerebral ischemia at various time points poststroke.     

Ghrelin对脑缺血再灌注大鼠脑水肿和水通道蛋白4表达的影响

 目的： 探讨ghrelin对脑缺血再灌注大鼠脑水肿、血脑屏障通透性及水通道蛋白4（AQP4）表达的影响。方法： 成年SD雄性大鼠随机分为3组:sham组、大脑中动脉阻塞（MCAO）组和ghrelin处理组。采用线栓法复制MCAO模型（缺血2 h,再灌注22 h）。Ghrelin组大鼠于再灌开始时经股静脉注射ghrelin 10 nmol/kg。TTC染色观察脑梗死体积,神经功能评分判断脑功能障碍程度,分别以体积计算和干湿重法检测脑肿胀程度和脑含水量的变化,收集脑血管外伊文思蓝(EB)来评估血脑屏障的破坏程度,免疫组化和Western blotting检测AQP4的表达变化。结果： 与MCAO组比较,ghrelin处理组的脑梗死体积较小（P<0.01）,神经功能评分较低（P<0.01）,脑组织中的EB渗出量较少（P<0.01）。Ghrelin处理组大鼠的脑肿胀体积、脑含水量和AQP4表达明显低于MCAO组（P<0.05）。结论： Ghrelin减轻大鼠脑缺血/再灌注损伤,减轻脑水肿和血脑屏障的破坏,抑制脑组织中AQP4的表达。AQP4在ghrelin的脑保护机制中可能发挥重要作用。     

缺血后适应对大鼠脑缺血/再灌注损伤的影响

目的：探讨缺血后适应对大鼠脑缺血/再灌注损伤的影响。方法:应用线栓法制作大鼠脑缺血/再灌注损伤模型；21只雄性SD大鼠随机分为缺血/再灌注组、夹闭单侧颈总动脉后处理组和夹闭双侧颈总动脉后处理组，每组7只。再灌注48 h，测定脑梗死体积；拔栓后1 h及处死大鼠前进行神经功能测定；梗死即刻、梗死后10 min、术中1 h、拔栓后即刻、每次夹/松颈总动脉时、干预后30 min等15个时点监测脑血流。结果:夹闭单侧、双侧颈总动脉后处理组大鼠脑组织梗死体积与缺血/再灌注组相比明显减小，有显著差异；3组脑血流各个时点方差分析差异无显著，但是夹闭双侧颈总动脉后处理组干预30 min后脑血流百分比较缺血/再灌注组、夹闭单侧颈总动脉后处理组降低9％。手术后1 h 3组神经功能评分P<0.05，差异显著，夹闭单侧、双侧颈总动脉后处理组神经功能缺损均比缺血/再灌注组减轻。结论:缺血后适应能够明显减小梗塞体积，改善大鼠术后1h神经功能评分，可能与缺血后适应调节早期再灌注时血流动力学状态有关。     

尼古丁对大鼠局灶性脑缺血再灌注损伤的神经保护作用

目的:研究尼古丁对大鼠局灶性脑缺血再灌注损伤是否具有神经保护作用。方法:在大鼠大脑中动脉堵塞(MCAO)前30min给予腹腔注射尼古丁酒石酸盐溶液,观察局灶性脑缺血2h再灌注24h后,大鼠神经行为学评分及脑梗死容积的变化。结果:再灌注24h后,与单纯缺血再灌注组相比,给予尼古丁酒石酸盐溶液注射可以改善动物的神经行为学评分、减少脑梗死容积百分比(P0.05)。结论:尼古丁对大鼠局灶性脑缺血再灌注损伤具有神经保护作用。     

局灶性脑缺血预处理上调大鼠梗死区周围巢蛋白的表达

目的 观察局灶性脑缺血预处理(IP)对巢蛋白(NESTIN)表达的影响,探讨NESTIN与脑缺血耐受(BIT)的关系及可能的内源性神经保护机制.方法 45只SD雄性大鼠随机分为脑缺血预处理(CIP)组、大脑中动脉阻塞(MCAO)组、假手术(sham)组.采用TTC染色测定脑梗死体积,光镜下观察脑组织病理改变,免疫组织化...     

Baicalin Inhibits TLR2/4 Signaling Pathway in Rat Brain Following Permanent Cerebral Ischemia

Recent work from our laboratory demonstrated that baicalin attenuates inflammatory reaction and cerebral ischemia injury in rats. Toll-like receptor 2 and 4 (TLR2/4) and the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which mediate the inflammatory reaction, are involved in the pathophysiological processes of cerebral ischemia. In this study, we investigated whether baicalin inhibits TLR2/4 signaling pathway in a rat model of permanent focal cerebral ischemia. Adult Sprague–Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administered by intraperitoneally injected twice at 2 and 12 h after the onset of ischemia. Cerebral infarct area and infarct volume were measured 24 h after MCAO. Expression of TLR2/4, NF-κB, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR or western blot. NO and PGE2 production in rat brain were measured 24 h after MCAO. Serum content of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. Baicalin reduced cerebral infarct area and infarct volume. Baicalin reduced the expression of TLR2/4 and NF-κB, decreased the expression and activity of iNOS and COX-2 in rat brain. Baicalin also attenuated the serum content of TNF-α and IL-1β. Our results suggest that baicalin inhibits the TLR2/4 signaling pathway in cerebral ischemia, which may be a mechanism underlying the baicalin’s neuroprotection.     

葡萄糖转运体3在脑缺血/再灌注后半影区表达的变化及意义

目的:研究大鼠局灶性脑缺血不同缺血时间和不同再灌注时间的脑梗塞体积比、皮质半影区葡萄糖转运体3(GLUT3)转录水平和蛋白水平的表达。方法:用线栓法复制大鼠局灶性脑缺血模型,用Kontron IBAS2.5全自动图像分析系统检测脑梗塞体积比;剥取缺血半影区皮质组织,采用反转录-聚合酶链反应(RT-PCR)测定GLUT3 mRNA水平的变化;用免疫组织化学方法半定量测定GLUT3蛋白水平的变化。结果:脑缺血1 h后再灌注组的脑梗塞体积明显小于缺血3 h再灌注组梗塞体积。GLUT3自3 h即开始升高,24 h到达高峰,1周时仍高于假手术对照组;缺血3 h再灌注组在3 h有一下降点,然后升高,24 h到高峰,1周时接近正常水平。GLUT3蛋白水平的表达与mRNA相符合。结论:GLUT3在缺血半影区的表达上调,可能是机体对缺血／再灌注的保护性反应。     

Hyperbaric oxygen preconditioning reduces ischemia–reperfusion injury by inhibition of apoptosis via mitochondrial pathway in rat brain

This study examined the hypothesis that apoptotic inhibition via mitochondrial pathway was involved in hyperbaric oxygen preconditioning (HBO-PC)–induced neuroprotection on ischemia–reperfusion injury in rat brain. Male Sprague–Dawley rats (250∼280 g, n=144) were divided into control, middle cerebral artery occlusion (MCAO) for 90 min, and HBO-PC plus MCAO groups. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at 12 h intervals for 2 days. At 24 h after the last HBO-PC, MCAO was performed and at 24 h after MCAO, neurological function, brain water content, infarct volume, and cell death were evaluated. Enzymatic activity of capase-3 and −9, and expression of cytochrome c, Bcl-2 and Bax proteins were performed in the samples from hippocampus, ischemic penumbra and core of the brain cortex, respectively. HBO-PC reduced brain edema, decreased infarction volume, and improved neurological recovery. HBO-PC reduced cytoplasm cytochrome c levels, decreased caspase enzyme activity, upregulated the ratio of Bcl-2 and Bax expression, and abated the apoptosis of ischemic tissue. HBO-PC protects brain tissues from ischemia–reperfusion injury by suppressing mitochondrial apoptotic pathways.     

Zileuton Reduces Inflammatory Reaction and Brain Damage Following Permanent Cerebral Ischemia in Rats

5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-κB) p65 in rat brain was detected by immunohistochemistry and Western blot. Expression of inducible nitric oxide synthase (iNOS) in rat brain was determined by RT-PCR and Western blot. Nitric oxide production in rat brain was also measured 24 h after MCAO. The concentration of TNF-α and IL-1β in serum were detected by ELISA. Zileuton significantly reduced neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-κB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-α and IL-1β in serum. Our results suggest that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction.     

CEPO经Mashl信号促进大鼠局部脑缺血后纹状体内神经发生

为检测氨甲酰化促红细胞叶三成素(CEPO)在大鼠脑缺血后发生过程中的作用及其相关信号通路,本实验将成年大鼠大脑中动脉栓塞(MCAO)后立即尾静脉给予CEPO(50μg/kg).结果显示:CEPO可显著降低大鼠MCAO后3 d梗塞面积,增加缺血侧神经于细胞增殖、促进神经干细胞分化成为神经元.CEPO的促神经发生效应与缺血侧纹状体内前神经元bHLH转录因子Mash1的表达上调密切相关.本结果提示CEPO对脑缺血具有神经保护作用,Mash1信号在缺血侧纹状体内可能介导CEPO增强的神经发生和神经元分化效应.     

咪唑安定对脑缺血/再灌注大鼠顶叶碱性成纤维细胞生长因子表达的调节作用

目的观察咪唑安定对大鼠脑局灶性缺血/再灌注脑组织碱性成纤维细胞生长因子(bFGF)表达水平的影响,从而探讨咪唑安定对脑缺血的作用机制。方法采用可逆性大脑中动脉缺血再灌注模型,再灌注同时腹腔注射咪唑安定50 mg.kg-1,再灌注6 h、24 h后断头取脑。观察大鼠梗死体积的变化,用免疫组织化学方法及W estern-b lot方法观察缺血区bFGF的表达,并进行显微图像分析。结果顶叶缺血区周围组织可见bFGF阳性表达产物,正常大鼠未见bFGF阳性表达产物,咪唑安定组与生理盐水组(NS)相比梗死灶体积缩小,免疫组化结果显示咪唑安定组脑缺血灶周围bFGF的平均光密度值高于NS组(P<0.05),阳性细胞主要以神经元、神经胶质细胞为主。W estern-b lot结果表明咪唑安定组整合光密度值与β-actin比值显著高于NS组(P<0.05)。结论咪唑安定对脑缺血性损伤的恢复作用可能与提高缺血周围区bFGF的表达有关。     

Effect of pioglitazone treatment on behavioral symptoms in autistic children

Introduction  

Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARγ), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism.     

Decrease of the electroacupuncture-induced analgesic effects in nuclear factor-kappa B1 knockout mice

We investigated whether pre-treatment with melatonin, a potent free radical scavenger and antioxidant, would protect against permanent focal cerebral ischemia without reperfusion in a rat middle cerebral artery occlusion (MCAO) model. A single dose of melatonin at 5, 15, or 50 mg/kg or the vehicle alone was given via an intraperitoneal injection at 0.5 h before permanent MCAO. Relative infarction volumes on day 3 were significantly reduced in the groups treated with melatonin at 5 (mean+/-SEM, 17.0+/-6.5%), 15 (18.1+/-5.8%), or 50 (20.6+/-5.0%) mg/kg when compared with the vehicle-treated group (37.1+/-2.8%) and so melatonin treatment achieved a relative reduction in infarct volume by 54.2, 51.2 and 44.5%, respectively. Melatonin did not affect the hemodynamic parameters. Thus, pre-treatment with melatonin at a dose between 5 and 50 mg/kg protects against focal cerebral ischemia without reperfusion.     

Comparison between coated vs. uncoated suture middle cerebral artery occlusion in the rat as assessed by perfusion/diffusion weighted imaging

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated thresholds and correlated with infarct volume corrected for edema defined by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 24 h after MCAO. The ADC/CBF-defined mismatch volume in the 4-0 coated suture model was present significantly longer (up to 120 min) compared to the uncoated 3-0 suture model (30 min). The TTC-derived infarct volume was significantly larger in the coated model (290.3+/-32.8 mm(3)) relative to the uncoated model (252.3+/-34.6 mm(3)). This study demonstrates that the type of suture may significantly influence the spatiotemporal evolution of the ADC/CBF-mismatch as well as the final infarct volume. These inter-model variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.     

Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model

Hyperglycemia is one of the major factors for hemorrhagic transformation after ischemic stroke. In this study, we tested the effect of hydrogen gas on hemorrhagic transformation in a rat focal cerebral ischemia model. Sprague–Dawley rats (n=72) were divided into the following groups: sham; sham treated with hydrogen gas (H₂); Middle Cerebral Artery Occlusion (MCAO); and MCAO treated with H₂ (MCAO+H₂). All rats received an injection of 50% dextrose (6 ml/kg i.p.) and underwent MCAO 15 min later. Following a 90 min ischemic period, hydrogen was inhaled for 2 h during reperfusion. We measured the level of blood glucose at 0 h, 0.5 h, 4 h, and 6 h after dextrose injection. Infarct and hemorrhagic volumes, neurologic score, oxidative stress (evaluated by measuring the level of 8 Hydroxyguanosine (8OHG), 4-Hydroxy-2-Nonenal (HNE) and nitrotyrosine), and matrix metalloproteinase (MMP)-2/MMP-9 activity were measured at 24 h after ischemia. We found that hydrogen inhalation for 2 h reduced infarct and hemorrhagic volumes and improved neurological functions. This effect of hydrogen was accompanied by a reduction of the expression of 8OHG, HNE, and nitrotyrosine and the activity of MMP-9. Furthermore, a reduction of the blood glucose level from 500±32.51 to 366±68.22 mg/dl at 4 h after dextrose injection was observed in hydrogen treated animals. However, the treatment had no significant effect on the expression of ZO-1, occludin, collagen IV or aquaporin4 (AQP4). In conclusion, hydrogen gas reduced brain infarction, hemorrhagic transformation, and improved neurological function in rats. The potential mechanisms of decreased oxidative stress and glucose levels after hydrogen treatment warrant further investigation.     

Activation of phosphatidylinositol 3-kinase/protein kinase B pathway by a vanadyl compound mediates its neuroprotective effect in mouse brain ischemia

We previously reported that orthovanadate composed of vanadate (V(5+)) activates phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling through inhibition of protein tyrosine phosphatases, thereby eliciting neuroprotection in brain ischemia/reperfusion injury. However, therapeutic doses of orthovanadate are associated with diarrhea due to inhibition of ATPase. By contrast, vanadyl (V(4+)) organic compounds show low cytotoxicity. Since both vanadate and vanadyl inhibit protein tyrosine phosphatases, we tested whether bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) [VO(OPT)] in a vanadyl form elicits a neuroprotection in brain ischemia. In a mouse transient middle cerebral artery occlusion (MCAO) model, pre- and post-treatments with VO(OPT) significantly reduced infarct volume in a dose-dependent manner. Like orthovanadate, activation of the PI3K/Akt pathway mediated neuroprotective action. VO(OPT) treatment inhibited reduced Akt phosphorylation at Ser-473 following brain ischemia and restored decreased phosphorylation of forkhead box class O (FOXO) family members such as FKHR, FKHRL1, and AFX. Consistent with inhibition of FOXO dephosphorylation, VO(OPT) treatment blocked elevated expression of Fas-ligand, Bim and active caspase-3 24 h after ischemia/reperfusion. Taken together, a vanadyl compound, VO(OPT) elicits neuroprotective effects on brain ischemia/reperfusion injury without apparent side effects.     

Rapid tolerance to focal cerebral ischemia in rats is induced by preconditioning with electroacupuncture: window of protection and the role of adenosine

The aim of the present study was to investigate the first protective window of preconditioning with electroacupuncture (EA) against focal cerebral ischemia, and to explore whether adenosine is involved in the rapid tolerance phenomenon. Sixty-four male Sprague-Dawley rats were randomly assigned to eight groups (n=8 in each). Animals in the control group received no treatment, and animals in EA1-EA4 groups received EA at 0.5, 1, 2 and 3 h before induction of focal cerebral ischemia, respectively. Rats in DPCPX group were intraperitoneally injected with 1 mg kg-1 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 3 h before induction of focal cerebral ischemia. Animals in vehicle group and EA+DPCPX group were pretreated with 1 ml kg-1 dimethyl sulfoxide (DMSO, the solvent of DPCPX) and 1 mg kg-1 DPCPX 30 min before preconditioning with EA, respectively. All rats were anesthetized with 40 mg kg-1 pentobarbital sodium intraperitoneally. Animals that required EA preconditioning, received EA with intensity of 1 mA and frequency of 15 Hz at the Baihui acupoint (GV 20) for 30 min. The focal cerebral ischemia was produced by the right middle cerebral artery occlusion (MCAO) for 120 min. The neurologic deficit scores (NDS) and brain infarct volumes were evaluated at 24 h after reperfusion. All rats survived until 24 h after reperfusion. Preconditioning with EA at 2 h before induction of focal cerebral ischemia improved neurologic outcome (P<0.05 versus control) and reduced the infarct volume (P<0.01 versus control) at 24 h after reperfusion. These beneficial effects were reversed by pretreatment with 1 mg kg-1 DPCPX, whereas this agent itself did not affect the NDS and volume in drug-ischemic controls after ischemia. The results show that preconditioning with single EA session induces rapid tolerance to focal cerebral ischemia. The rapid ischemic tolerance appears at 2 h (but not at 0.5, 1, or 3 h) after preconditioning, and is possibly mediated through an adenosine A1 receptor-related mechanism.     

肢体缺血后适应对小鼠脑缺血再灌注损伤的影响及机制

目的:建立小鼠脑缺血后进行短暂肢体缺血提高脑缺血耐受模型,确定肢体缺血后适应对脑缺血时程的影响及热休克蛋白70(HSP70)的作用,探讨肢体缺血后适应(LIPostC)对脑缺血/再灌注损伤抑制作用和机制。方法:复制小鼠大脑中动脉闭塞模型(MCAO),第1批实验将小鼠分为9组:假手术组、脑缺血/再灌注组(缺血时间分别0.5 h、1 h、1.5 h、2 h组),脑缺血/再灌注+短暂肢体缺血(LIPostC)组(0.5 h+LIPostC、1 h+LIPostC、1.5 h+LIPostC、2 h+LIPostC组)。分别观察小鼠运动行为变化;TTC染色测量脑梗死体积;HE染色观察脑组织损伤程度;TUNEL法检测神经元凋亡程度。第2批实验将小鼠随机分为4组:假手术组、脑缺血/再灌注组、MCAO+LIPostC组和MCAO+LIPostC+quercetin组(缺血时间为2 h)。术后24 h用Western blotting法检测脑皮质中HSP70蛋白表达和神经功能评分。结果:脑缺血时程影响小鼠运动行为和脑损伤程度,随脑缺血时间延长,小鼠的脑再灌注损伤程度加重,其行为缺陷和脑病理变化明显;缺血2 h组脑损伤程度比缺血1.5 h组和缺血1 h组严重(P0.05)。脑缺血后不同时间施加LIPostC显示不同程度的神经保护作用。LIPostC各组与相对应的I/R组比较,其脑再灌注损伤程度呈现不同程度减轻,行为学评分降低、脑梗死体积减小,脑皮质损伤减轻,TUNEL阳性凋亡细胞数目减少。脑缺血2 h再灌注损伤较重,但LIPostC仍具有明显的脑保护作用。以2 h脑缺血小鼠为模型进行机制研究,结果表明,LIPostC可提高缺血脑组织HSP70蛋白表达,改善神经功能,HSP70抑制剂quercetin可削弱LIPostC的这种脑保护作用。结论:LIPostC可抑制MCAO小鼠的脑缺血再灌注损伤,促进缺血脑区HSP70表达和改善神经功能。HSP70在LIPostC提高MCAO小鼠的脑缺血耐受机制中发挥重要作用。     

Beneficial effects of thiazolidinediones on diabetic nephropathy in OLETF rats

PURPOSE: Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF. MATERIALS AND METHODS: 23 Otsuka- Long-Evans-Tokushima-Fatty (OLETF) rats and eight control Long-Evans-Tokushima-Otsuka (LETO) rats were divided into the following four groups: LETO group, control OLETF group, pioglitazone treated group (10mg/ kg/day), and rosiglitazone treated group (3mg/kg/day). RESULTS: A progressive increase in urinary protein excretion was observed in the diabetic rats. Glomerular VEGF expression in the control OLETF rats was significantly higher than in the control LETO rats. However, there was a significant reduction in both the glomerular VEGF expression and the VEGF mRNA levels after treatment with pioglitazone and rosiglitazone. The twenty-four hour urine protein levels were significantly decreased in both groups of the treated OLETF rats. CONCLUSION: These results suggest that TZD may have beneficial effects on diabetic nephropathy by reducing the VEGF expression.