1,6-二磷酸果糖治疗新生儿缺氧缺血性脑病的疗效观察

我科自2001年以来，应用1，6-二磷酸果糖（FDP）治疗新生儿缺氧缺血性脑病40例，现报告如下。     

1,6-二磷酸果糖治疗新生儿缺氧缺血性脑病疗效分析

新生儿缺氧缺血性脑病(HIE)是围产期足月儿和早产儿易合并的严重疾病,可导致神经系统后遗症或死亡.我院儿科对足月儿及早产儿采用1,6-二磷酸果糖治疗HIE,取得良好疗效,现报道如下.     

1,6-二磷酸果糖联合甲钴胺治疗糖尿病周围神经病变的疗效观察

目的观察1,6-二磷酸果糖(FDP)联合甲钴胺治疗糖尿病周围神经病变(DPN)的临床疗效.方法119例DPN患者随机分为两组.对照组55例,给予甲钴胺500μg肌肉注射,每日1次;治疗组64例,在甲钴胺治疗基础上加用FDP 10g静滴,每日1次.两组疗程均为20d.结果治疗组有效率93.8%,对照组有效率74.5%.两组疗效和症状恢复正常的时间均有显著性差异(P＜0.01或0.05).结论FDP联合甲钴胺是治疗DPN安全、有效的方法.     

1,6—二磷酸果糖对缺血性脑组织的保护作用

本文综述了FDP对缺血性脑组织的保护作用,FDP能增加脑缺血时ATP含量,对脑组织代谢功能有独特的保护作用,减少氧自由基对脑组织损害,恢复血流再灌流后的脑组织功能,增加红细胞膜韧性,有助于血红蛋白与组织之间的氧交换。增加缺血组织对氧的利用。     

脑出血后高血糖血肿周围脑组织ATP与NO的关系研究

目的观察大鼠脑出血（ICH）后高血糖对血肿周围脑组织NO和三磷酸腺苷（ATP）的影响,探讨ICH后高血糖对脑损伤的可能机制。方法采用自体血注入法建立脑出血模型,将SD大鼠随机分成假手术组（SO）、单纯脑出血组（PCH）、脑出血后高血糖组,脑出血后后高血糖组又分为2 g/kg（2G组）和4g/kg（4G组）注射葡萄糖组,并观察各组大鼠术前、术后1、6 h血糖变化;测定各组大鼠术后1、3、7、10、14 d血肿周围脑组织NO和三磷酸腺苷（ATP）含量变化。结果与SO组比较,脑出血3组血肿周围脑组织NO含量升高,ATP含量降低（P〈0.05）;与PCH组比较,2G组和4G组大鼠血肿周围脑组织NO含量明显升高（P〈0.05）,ATP含量明显降低（P〈0.05）,以4G组变化更明显（P〈0.05）。结论脑出血后高血糖可能通过NO的毒性作用加重能量代谢障碍,而加重脑损伤。     

兔脑出血后血肿周围组织ATP和乳酸含量及磷酸果糖激酶活性变化

目的　观察兔脑出血后血肿周围组织能量代谢产物的变化规律。方法　健康大耳白家兔采用随机数字法分成 3组 :正常组 ,脑出血组 ,假手术组。其中脑出血、假手术组又分成 1、6、12、2 4、4 8、72h组。采用二次注血法制备兔自体血脑出血模型。分离血肿周围组织 ,测定脑水含量、能量代谢产物三磷酸腺苷 (ATP)和乳酸的含量以及磷酸果糖激酶活性变化。结果　脑出血 1h血肿侧即有脑水肿 ,至 72h逐渐加重 ,血肿侧明显重于对侧。 1h后血肿周围组织ATP含量呈中度下降 ,但差异无显著意义。 1～ 12h间ATP含量略有波动 ,12h后再次下降 ,至 2 4h达最低点 [(13 2 9± 2 92 )μg/ g ,降至正常的 5 8% ],差异有显著意义。 2 4h至 72h间无明显变化。乳酸含量于 1h即有增高 ,12h达高峰 [(2 1 0 1± 0 18) μmol/g],直至 72h乳酸水平 [(12 89± 0 2 5 ) μmol/g]仍明显高于正常组及假手术组。磷酸果糖激酶 (PFK)活性 1h即有下降 [(3 98± 0 0 2 )U/mg],72h内持续下降。与正常组及假手术组比较差异有显著意义。结论　脑出血后血肿周围组织在 2 4h后才发生明显的能量代谢衰竭 ,滞后于脑水肿的发生 ,其发生机制可能与相关酶的活性减低有关     

实验性脑出血血肿周围组织中Rho激酶的研究

目的观察实验性脑出血(ICH)血肿周围组织中Rho激酶的表达及其与神经功能缺损的关系。方法将ICH模型大鼠随机分为ICH后1d、3d、5d及7d组;在相应时间点处死大鼠前进行神经功能评分;运用免疫组化法和原位杂交法观察每组大鼠血肿周围脑组织中Rho激酶蛋白及mRNA的表达。结果ICH后1d、3d、5d及7d组神经功能评分分别为1.63、2.25、3.13及2.88;血肿周围脑组织Rho激酶蛋白阳性细胞数分别为26.63、30.75、38.88及35.00;血肿周围Rho激酶mRNA阳性细胞数分别为27.25、32.25、40.88及38.00。1d、3d、5d组间神经功能评分、Rho激酶蛋白及mRNA的表达差异有统计学意义(P<0.05～0.01),5d组与7d组间差异无统计学意义;神经功能评分与Rho激酶蛋白及mRNA的表达呈正相关(r1=0.534,r2=0.675,均P<0.01)。结论ICH后血肿周围脑组织中Rho激酶可能被激活,并参与了ICH后血肿周围脑组织的损害过程。     

1,6-2磷酸果糖治疗新生儿缺氧缺血性脑病合并心肌损害30例疗效观察

我院儿科于2002～03～2004～09共收治新生儿缺氧缺血性脑病(HIE)患儿161例,合并心肌损害65例,其中30例在常规治疗基础上加用1,6-2磷酸果糖(1,6-FDP)治疗,取得一定疗效,现报告如下。1临床资料本组男38例,女27例,阿氏评分<3分31例,4～7分34例。HIE轻度5例,中度41例,重度19例。HIE诊断标准依据韩玉昆等的HIE诊断依据和分度方法〔1〕。新生儿缺氧缺血性脑病合并心肌损害诊断标准:(1)符合HIE诊断标准;(2)除外宫内病毒感染;(3)临床表现心音低钝,心率异常(<100次/min或心率增快>160次/min);(4)心电图在生后24h仍有2个以上导联S-T段移位,伴…     

高血压脑出血患者血肿周围血-脑屏障超微结构的观察

目的 动态观察高血压脑出血后不同时间血肿周围血-脑屏障（BBB）的超微结构。方法 选取10例基底节区高血压脑出血患者,通过CT导向脑立体定向仪在血肿周围取脑组织标本,电镜下观察BBB的超微结构。结果：脑出血12h后BBB胶质足板水肿,胞饮水泡增多,24h后内皮细胞线粒体肿胀,嵴断裂,48h后足板水肿明显,内皮细胞水肿,细胞核增大;72h胞质稀疏,基底膜断开;5d内皮细胞胞膜及核膜溶解,毛细血管塌陷。结论 脑出血早期预防BBB的损害是治疗脑出血的重要方面。     

1,6-2磷酸果糖治疗新生儿缺氧缺血性脑病合并心肌损害30例疗效观察

我院儿科于2002～03-2004～09共收治新生儿缺氧缺血性脑病（HIE）患儿161例,合并心肌损害65例,其中30例在常规治疗基础上加用1,6-2磷酸果糖（1,6-FDP）治疗,取得一定疗效,现报告如下。     

Df—521巴曲酶对大鼠脑出血后脑水肿形成的影响

目的:观察Df-521巴曲酶对大鼠脑出血后脑水肿对血肿周边区脑组织ICAM-1表达的影响。方法:一侧基底节注射自体血制作大鼠脑出血模型,用干湿重法,测定脑组织含水量;用免疫组化法检测血肿周边水肿带ICAM-1的表达情况。结果:大鼠脑出血后,血肿侧脑组织含水量上升,同时水肿区ICAM-1的表达量增加;给予Df-521巴曲酶制剂处理后,血肿侧脑水肿减轻,脑组织ICAM-1的表达有所下降。结论:Df-521巴曲酶能下调脑出血后血肿周边组织ICAM-1的表达并减轻脑水肿的程度。     

DF-521巴曲酶对大鼠脑出血后脑水肿区补体表达的影响

目的 :观察降纤酶制剂对大鼠脑出血后脑水肿形成及血肿周边脑组织补体C3d和C9表达的影响。方法 :一侧基底节区注射自体血 10 0 μL制作大鼠脑出血 2 4、72h模型 ,一组给予腹腔注射降纤酶制剂DF 5 2 1巴曲酶处理 ,一组不给 ,另设一组空白对照脑内注射生理盐水 10 0 μL。用干湿重法 ,测定大鼠脑组织的含水量 ;免疫组化法检测C3d的表达 ,免疫Westernblot方法研究脑组织补体C9表达情况。结果 :大鼠脑出血后 ,血肿侧脑组织含水量上升 ,同时出血侧脑组织内C3d和C9的表达量增加 ;给予DF 5 2 1巴曲酶制剂处理后 ,血肿侧脑水肿减轻〔2 4h由 (81 8± 1 14 ) %降至 (79 46± 0 68% ) ,P <0 0 1;72h由 (83 14± 0 3 6) %降至 (81 0 9±0 3 4) % ,P <0 0 1〕 ;并且脑组织C3d和C9的表达较对照组有所下降。结论 :降纤酶制剂能下调脑出血后血肿周边脑组织补体C3d和C9的表达并减轻大鼠脑出血后脑水肿的程度。     

4-苯基丁酸对大鼠脑出血模型脑水肿的作用及机制探讨

目的探讨4-苯基丁酸(PBA)对大鼠脑出血(ICH)后脑水肿的作用及机制。方法健康雄性SD大鼠,随机分为ICH组、PBA 100 mg·kg-1组、PBA 300 mg·kg-1组(均n=15)和假手术组(n=9),采用自体血脑内立体定向注射法建立大鼠ICH模型,不同剂量组PBA干预组于术后即刻每24 h腹腔注射相应剂量的PBA,评价术后不同时间点各组大鼠神经功能评分。各组大鼠均于术后72 h处死,干湿重法检测脑水肿情况,伊文思蓝法检测血脑屏障通透性变化,同时Western blot法检测血肿周围脑组织中基质金属蛋白酶9(MMP-9)表达的变化。结果 PBA 300 mg·kg-1组各时间点神经功能缺损显著低于ICH组(P0.05)。ICH后72 h,PBA 100 mg·kg-1组、PBA 300 mg·kg-1组脑组织含水量和伊文思蓝含量显著低于ICH组(P0.05);血肿周围组织中MMP-9表达也显著低于ICH组(P0.05)。结论 PBA能够改善大鼠ICH模型的神经功能缺损,减轻ICH后水肿和改善血脑屏障通透性,抑制血肿周围脑组织中MMP-9的表达是可能作用机制。     

Changes of Blood Flow Perfusion by MR and NF-κβ Expression in the Region of Perihematoma after Experimental Intracerebral Hemorrhage: A Correlation Study

Objective: Tostudy the correlation between dynamic changes of regional cerebral blood flow (rCBF) and nuclear factor-kappa β (NF-κβ) expression in the region of perihematoma after intracerebral hemorrhage (ICH). Methods: Twenty-seven healthy domestic cats were divided into control group (n = 3) and ICH group (n = 24) at random. They were observed at 3 hr, 6 hr, 12 hr, 24 hr, 48 hr, 72 hr, 7 days, and 15 days, respectively, for the dynamic changes of rCBF in the perihematomal region using perfusion-weighted imaging (PWI), and NF-κβ expressions using immunohistochemistry method. Results: In the perihematomal region, a noticeable decrease in rCBF had been observed within 12 hr, i.e. in a hypoperfusion state. However, cats then presented reperfusion or hyperperfusion during 12–24-hr period, and marginally hypoperfusion after 48 hr. NF-κβ positive cells were first found at 3–6 hr and peaked at 12–48 hr. At 72 hr to 7 days they showed a decreasing trend and nearly disappeared at 15 days. Conclusions: NF-κβ expression was significantly increased due to ischemia reperfusion in the perihematomal region after cerebral ischemia, and the resulting inflammatory and immune reaction were the major causes for ischemia reperfusion injury in the perihematomal region.     

脑出血大鼠血肿周围脑组织细胞间黏附分子的表达与脑水肿的关系

目的探讨脑出血后血肿周围脑组织炎性损伤的病理发展过程。方法健康Wistar大鼠48只随机分成脑出血组、对照组。分别于制模后3h、24h、72h、7d取血肿周围脑组织检测细胞间黏附分子(ICAM-1)的表达,并对出血侧脑组织含水量进行测定。结果脑出血组各时相点出血周围组织均有ICAM-1阳性反应的血管和神经细胞,与对照组比差异有极显著性(P<0·01);与对照组比较,脑出血3h组血肿周围组织含水量即开始升高,24h明显增加(P<0·01),72h仍高于对照组,7d时接近对照组。结论ICAM-1在血肿周围的高表达可能是脑出血后血肿周围组织受损的主要原因之一,ICAM-1促进白细胞浸润,释放大量氧自由基,继而导致脂质过氧化加重脑组织损伤,并参与脑水肿的形成发展。     

大鼠脑出血后细胞色素c表达和神经细胞凋亡的关系及牛磺酸熊去氧胆酸的干预作用

目的研究大鼠脑出血(ICH)后细胞色素c(cytc)表达和神经细胞凋亡的关系,探讨牛磺酸熊去氧胆酸(Tudca)的干预作用及其机制。方法用VII型胶原酶注入到大鼠右侧苍白球诱导ICH模型。用凋亡原位末端标记技术(TUNEL)和免疫组化方法检测血肿周围神经细胞凋亡和cytc表达的动态变化。透射电镜观察术后3d血肿周围神经元超微结构的变化。结果:ICH后6h cytc表达开始增加,1d达高峰,此后逐渐减少,7d时回落至假手术组水平。ICH后6h血肿周边组织可见TUNEL阳性细胞,3d达高峰,然后逐渐减少,7d、10d时仍见较多凋亡细胞。ICH后7d内cytc表达和神经细胞凋亡呈正相关(r=0.6357,P<0.01)。Tudca治疗组cytc和TUNEL阳性细胞数较模型组明显减少(P<0.05~0.01),神经元超微结构改变亦比模型组减轻。结论ICH后血肿周围神经细胞损伤有凋亡机制参与,cytc释放是神经细胞凋亡的一个关键事件,Tudca可以有效减轻脑出血后的细胞凋亡,其机制之一是抑制凋亡通路cytc的释放。     

Thy-1 cell surface antigen on cloned cell lines of the rat and mouse: Stimulation by cAMP and by butyrate

The level of the Thy-1 cell surface antigen on a number of established rat and mouse nerve cell lines can be stimulated by N6, O2'-dibutyryl adenosine 3':5'-cyclic monophosphoric acid (Bt2cAMP), in some cases up to the antigen level found in whole brain. On rat cell line BN1010-3, stimulation is also produced by phosphodiesterase inhibitors, adenosine 3':5'-cycle monophosphoric acid (cAMP) and its 8-bromo derivative, and L-isoproterenol. Hence, antigen elevation appears to occur via cAMP-related metabolism. It is not a consequence of morphological changes brought about by cAMP elevation in these cells, and is apparently independent of the inhibition of cell division by the nucleotide. Elevations of intracellular cAMP levels for at least one hour are needed to produce Thy-1 stimulation, after which an enhanced level of Thy-1 is observable after about 12 h. Continuous stimulation is required to maintain elevated antigen levels, for upon removal of the stimulating agent, the level of Thy-1 returns to the original unstimulated value within 48 h. Potent stimulation of the antigen level is also obtained with butyrate at 1--2 mM, which appears to be acting by a cAMP independent mechanism.     

Effects induced by cannabinoids on monoaminergic systems in the brain and their implications for psychiatric disorders

The endocannabinoid system and CB(1) receptors participate in the control of emotional behavior and mood through a functional coupling with the classic monoaminergic systems. In general, the acute stimulation of CB(1) receptors increases the activity (spontaneous firing rate) of noradrenergic (NE), serotonergic (5-HT) and dopaminergic (DA) neurons as well as the synthesis and/or release of the corresponding neurotransmitter in specific brain regions. Notably, the antagonist/inverse agonist rimonabant (SR141617A) can decrease the basal activity of NE and 5-HT neurons, suggesting a tonic/constitutive regulation of these neuronal systems by endocannabinoids acting at CB(1) receptors. Monoaminergic systems are modulated via CB(1) receptors by direct or indirect effects depending on the localization of this inhibitory receptor, which can be present on monoaminergic neurons themselves and/or inhibitory (GABAergic) and/or excitatory (glutamatergic) regulatory neurons. The repeated stimulation of CB(1) receptors is not associated with the induction of tolerance (receptor desensitization) on the activity of NE, 5-HT and DA neurons, in contrast to chronic agonist effects on neurotransmitter synthesis and/or release in some brain regions. CB(1) receptor desensitization may alter the direct and/or indirect effects of cannabinoid drugs modulating the functionality of monoaminergic systems. The sustained activation of monoaminergic neurons by cannabinoid drugs can also be related to changes in the function of presynaptic inhibitory α(2)-adrenoceptors or 5-HT(1A) receptors (autoreceptors and heteroreceptors), whose sensitivity is downregulated or upregulated upon chronic CB(1) agonist exposure. The functional interactions between endocannabinoids and monoaminergic systems in the brain indicate a potential role for CB(1) receptor signaling in the neurobiology of various psychiatric disorders, including major depression and schizophrenia as the major syndromes.     

The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes

Platelets have been extensively studied as hemostatic regulators, stopping uncontrolled flow of blood from an injured vessel and allowing for repair. However, multiple studies have shown that platelets can interact with bacterial proteins, particularly seen during sepsis and inflammation. Immune cells recognize pathogens through Toll-like Receptors (TLRs). These same receptors allow platelets to recognize bacterial proteins and regulate platelet immunity and function. This review examines the TLRs expressed on platelets and megakaryocytes and how these receptors affect the function of these cells. Through TLRs, platelets go beyond hemostatic regulation and play a pivotal role in inflammation and infection.