急性脑梗死血小板高尔基体变化及sCD40L对脑缺血损伤作用的实验研究
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摘要
第一部分急性脑梗死血小板高尔基体形态变化及其意义
背景：
脑梗死是严重危害人类健康和生命的常见疾病之一。然而,脑梗死的病理生理机制极为复杂。目前普遍认为,血小板活化是脑梗死发生的重要因素之一。已有大量研究发现,在梗死形成的整个过程中,血小板的粘附性和聚集性增加,并且能合成和释放多种促炎症因子。短暂性全脑缺血可引起血小板活化和脑内血小板聚集,而急性脑梗死患者血小板形态结构则发生明显改变。
高尔基体是与血小板合成和分泌功能有关的重要细胞器,是细胞分泌通路的中心环节,在物质的合成和转运方面发挥重要作用。本课题组前期研究发现,短暂性脑缺血后神经细胞高尔基体发生了明显的形态变化。有研究发现血小板无力症患者的血小板高尔基体形态和数量发生了明显的改变。
研究发现,糖尿病、高血压、高同型半胱氨酸血症等病人血清sCD40L水平增高,上述均为脑梗死常见危险因素。正常血小板胞浆内存在合成的CD40L,当血小板活化后由胞内转移至胞膜,在此分裂为可溶性片段释放,而sCD40L与膜结合性CD40L具有相同生物学效应。血中sCD40L约95%来自活化血小板,但目前CD40L由血小板内转移至胞膜并释放的具体途径还不清楚。
目的：
探讨急性脑梗死后血小板高尔基体的形态变化及其意义,以及高尔基体对血小板表达CD40L的作用。
方法：
1、选取20例急性脑梗死患者,分别在发病后第1、7、15天,各采集清晨空腹周围静脉血5ml,收集血小板,选取20位正常成人清晨空腹周围静脉血作对照。通过电镜对血小板超微结构、高尔基体等进行观察。通过免疫电镜的方法,用TGN46作为标记物对高尔基体进行定位观察。各组标本在放大15000倍视野下随机选取10个血小板,对10个血小板内的α颗粒总数进行计数并统计分析。
2、通过流式细胞术测量正常血小板在(静息、活化、先阻断高尔基体功能再活化)三种状态下的CD40L阳性表达率的变化(n=20)。
结果：
1、急性脑梗死后,各时间点血小板内α颗粒均明显减少(P<0.05),以第1天减少较为明显；
2、急性脑梗死后,血小板高尔基体小管和囊泡排列不规整、明显增粗、膨大；
3、免疫电镜试验发现脑梗死后,有α颗粒聚集分布在高尔基体小管和囊泡附近的现象,在发病后15天仍可见到上述变化；
4、高尔基体功能被阻断后,活化血小板表达CD40L明显减少(P<0.05)。
结论：
1急性脑梗死后血小板高尔基体发生明显的形态变化；
2高尔基体的结构改变可能与血小板活化后合成和分泌功能增强有关；
3高尔基体与血小板CD40L的表达有关。
第二部分sCD40L对脑缺血损伤作用的研究
背景：
脑梗死发病率、致残率及病死率均较高,病因复杂。吸烟,高血压、冠心病、高半胱氨酸血症、高脂血症均为脑梗死常见的危险因素,上述患者血中sCD40L明显增高。单纯颈动脉狭窄者血清sCD40L水平也高于正常对照。因此,有学者认为sCD40L可作为预测脑梗死的生物学指标,sCD40L升高与心脑血管疾病发生有关。
sCD40L是CD40L的可溶性形式。sCD40L可与三种受体结合：CD40、α5β1和αⅡbβ3,三者均可表达于血小板。CD40则主要表达于B细胞、活化T细胞、树突状细胞、内皮细胞、单核细胞/巨噬细胞以及中枢神经系统内多种细胞。sCD40L与CD40相互作用不但使脉管系统内产生ROS引起氧化应激,还能诱导人类血管内皮细胞表达粘附分子,并刺激释放趋化因子和细胞因子,上述分子参与动脉粥样硬化斑块的形成。SCD40L与α5β1和αⅡbβ3结合诱导血小板活化。
脑梗死发生后,血脑屏障破坏、白细胞浸润和小胶质细胞增殖活化是导致缺血性脑损伤的主要病理变化。活化的小胶质细胞CD40表达增加,体外研究发现CD40L与CD40相互作用可促进小胶质细胞活化,sCD40L水平升高是否加剧急性脑缺血后神经损伤,目前尚无此方面的研究。
目的：
研究sCD40L对脑缺血损伤的作用,探讨其可能的机制。
方法：
健康雄性SD大鼠(132只)随机分为6个试验组[假手术对照组、术后1d组、术后3d组、术后给药3d组(低剂量rsCD40L)、术后给药3d组(高剂量rsCD40L)、术后5d组](n=22)。参照文献,通过夹闭双侧颈总动脉和低血压的方法制作大鼠急性全脑缺血模型。两个给药组分别在术后第1、2天每日经尾静脉注射rsCD40L一次,参考有关文献,按lμg／kg(低剂量)和l0μg／kg(高剂量)给药,第3天取材。
假手术组于术后第一天处死,其余各组分别于第1d、3d、5d处死,每组大鼠中取4只用于HE染色和免疫组化及免疫荧光实验、6只用于脑组织含水量测定、6只用于血脑屏障通透性检测(在取材前2小时经尾静脉注射伊文斯蓝溶液,取材后检测脑组织中伊文斯蓝含量)、6只用于Western blot检测CD40.ClqA和NF-K Bp65在脑组织的表达情况。术中、术后死亡的动物从试验中剔除,做相应补充。
结果：
1 HE染色观察：
假手术组大脑皮层组织形态结构基本正常。脑缺血后1天组可见部分神经元轻度水肿、胶质细胞增生；3天组可见大量神经元存在核仁不清以及染色质边集的现象、并可见胶质细胞增生：5天组神经胶质细胞增生较明显明显,有嗜神经元现象。给药组可见胶质细胞有所增加、嗜神经元现象增多,以高剂量组改变较为明显。
2脑含水量和血脑屏障通透性结果：
急性脑缺血后脑含水量明显高于假手术组(p<0.05),伊文斯蓝含量也明显高于假手术组(p<0.05),rsCD40L给药组脑含水量和伊文斯蓝含量都显著高于假手术组(p<0.05),高剂量组明显高于低剂量组(p<0.05)。
3免疫组化和免疫荧光：
CD40主要表达于细胞膜,假手术组有少量阳性表达,脑缺血后阳性细胞增多,1天组可见阳性表达最多,5天组有所减少,3天低剂量组阳性表达多于3天组和5天组,3天高剂量组阳性表达明显多于其它各组。ClqA则表达于细胞浆,假手术组只有极少数阳性细胞,1天组表达增多。3天组较1天组表达有所增加,可见内皮细胞也有阳性表达。5天组与1天组表达较少。给药组ClqA阳性细胞明显增加,以高剂量组ClqA阳性细胞表达最多。NF-K Bp65免疫荧光发现,假手术组阳性表达细胞较少,1天组和3天组阳性细胞明显增多,5天组有所减少。给药组表达增加明显,可见NF-KBp65在胞浆和胞核都有表达,高剂量组胞核表达增多。
4 Western blot检测脑组织CD40.ClqA.NF-k Bp65蛋白的表达结果：
在假手术组中CD40少量表达、ClqA.NF-k Bp65有微量表达,1天组3天组和5天组CD40.C1 qA.NF-k Bp65表达均有所增加(p<0.05),CD40和NF-k Bp65表达在第1天时较为明显,3天和5天时二者表达有所减少1天时C1qA表达明显少于CD40和NF-k Bp65表达,在3天时C1qA表达最为显著,表达高峰迟于CD40和NF-k Bp65表达高峰。在给药组中,高剂量组比低剂量组的表达均有显著增加(p<0.05)。
结论：
1脑缺血后sCD40L加剧脑缺血损伤；
2急性脑缺血后CD40.ClqA.NF-K Bp65表达上调可能与sCD40L有关
Change of the Platelet Golgi Apparatus After Ischemic Stroke
Background:
Stroke, a brain attack, is the leading cause of disability and the third leading cause of death. Ischemic stroke is by far the most frequent type of stroke. Until now, platelet activation is thought to be a very important cause of the ischemic stroke. Studies showed that the conglutination and congregation of platelets increased significantly in the whole process of the infarction, the activated platelets synthesized and secreted multiple inflammatory factors. Transient ischemic induced platelet activation and platelet accumulation in the brain microvessels. Blood Platelet structure changed in the patients with stroke acute cerebrovascular infarction.
Golgi complex is an important organ of platelet, for its key role in synthesizing, secretion, and transportation. In our early research, we have found that the structure of neuron golgi complex changed during brain ischemia.
CD40L was transferred onto the membrane after platelet was activated, and then CD40L clipped into sCD40L. After acute ischemia, plasma sCD40L increased significantly. Platelet activation existed in the patients of diabetes, hypertension and Homocysteine(Hcy)with increased sCD40L expression. Almost 95% of sCD40L were from platelets in blood. Until now, the exact way of the CD40L transportation and secretion is not clear.
Purpose:
The aim of this study was to evaluate the structural change of the platelet Golgi apparatus after stroke, and to investigate the potential role of the Golgi apparatus in the expression of platelet CD40L
Methods:
Platelets of 20 patients were observed by electron microscopy and Immuno-electron microscopy with the platelets of 20 healthy volunteers as control. Suspensions of platelets got from 20 healthy volunteers were used to evaluated the role of the Golgi apparatus in the expression of CD40L on platelets by flow cytometry. The expression of CD40L on the activated platelets was observed after the Golgi apparatus was interdicted by the Brefeldin A(BFA) compared with normal platelets and the platelets activated by ADP.
Results:
The Golgi apparatus changed obviously after stroke, the main change was the increasing and widening of the Golgi vesicles and stacks, and there were some a granules around them.αgranules in platelet decreased significantly after stroke(P<0.05). The change remained obviously until the 15th day after stroke. The expression of CD40L on the activated platelets increased significantly compared with normal platelets(P<0.05). Compared with the platelets activated by ADP, the CD40L expression decreased on the platelets which the Golgi apparatus were interdicted by Brefeldin A before activated by ADP(P<0.05).
Conclusions:
The Golgi apparatus may play an important role in the pathophysiology of stroke. The Golgi apparatus may be a potential target for inhibition of CD40L synthesis and transfer in platelet.
The Effect of sCD40L on the Brain ischemic injury
Background:
After acute ischemic stroke, plasma sCD40L increased significantly. Platelet activation exist in patients of diabetes, hypertension, Homocysteine, and sCD40L increased in these patients.95 percent of sCD40L were from platelets in blood. sCD40L is now thought to be a marker to evaluate the severity of stroke. sCD40L increasing is related with the brain vascular disease.
SCD40L is soluble form of the CD40L. sCD40L can bind to three receptors(CD40,α5β1 and aⅡbβ3). All of the three receptors expressed on the platelet. CD40 expressed on B cells, activated T cells, DC, endothelium, monocyte, platelet and also expressed on many kinds of cells in CNS.
Breakage of BBB, leucocyte infiltration and microglia activation are main pathology changes after the onset of stroke. CD40 on the Activated microglia increased. sCD40L can activate microglia. There is no report on the relation of the sCD40L and brain ischemic injury so far.
Purpose:
Study the role of sCD40L in the brain ischemic injury. Investigate the potential mechanisms of sCD40L on the brain ischemic injury.
Methods:
132 SD rats were divided into 6 groups randomly which are control group. 1st day group,3th day group,5th day group, low dose rsCD40L group and high dose rsCD40L group. The control group were executed after one day. the rest groups were executed on the 1st.3th,5th day respectively. The methods of HE stain, immunochemistry, immunofluorescence, and western blot were put in use to observe the expression of the CD40, ClqA, NF-K Bp65 in the brain tissue after ischemia. The brain water content and the EB content in the brain tissue were also observed.
Results:
1 HE
The brain tissues are actually normal in the control group. The neuron death and microglia activation can be observed in the brain ischemic groups. These changes also exist in the 5th day group. The neuron death and microglia activation increased in the rsCD40L groups.
2 Brain water content and EB content
The brain water content and the EB content in the brain tissue increased significantly in the brain ischemic groups compared to the control group(p<0.05). Compared to the brain ischemic groups, a significant increase can also be observed in rsCD40L groups (p<0.05).
3 Immunochemistry and immunofluorescence
CD40 expressed on the membrane, ClqA expressed in the cytoplasm and the NF-kBp65 were observed both in the cytoplasm and nuclear. The expression of the three increased after brain ischemia.
4 Western blot
CD40, ClqA and NF-kBp65 expressed less in brain tissue, while increased at the 1,3,5 day(p<0.05)after brain ischemia. CD40 and NF-xBp65 increased significantly after brain ischemia(p<0.05). ClqA expression significantly increased at 3th day compare to other groups. All the three increased significantly in the high dose rsCD40L group compared to the low dose group (p<0.05).
Conclusions:
1 sCD40L strengthen the brain ischemic injury.
2 sCD40L may strengthen the brain ischemic injury via the activation of the complement and increasing of the inflammation in the ischemic brain tissue.
背景：
脑梗死是严重危害人类健康和生命的常见疾病之一。然而,脑梗死的病理生理机制极为复杂。目前普遍认为,血小板活化是脑梗死发生的重要因素之一。已有大量研究发现,在梗死形成的整个过程中,血小板的粘附性和聚集性增加,并且能合成和释放多种促炎症因子。短暂性全脑缺血可引起血小板活化和脑内血小板聚集,而急性脑梗死患者血小板形态结构则发生明显改变。
高尔基体是与血小板合成和分泌功能有关的重要细胞器,是细胞分泌通路的中心环节,在物质的合成和转运方面发挥重要作用。本课题组前期研究发现,短暂性脑缺血后神经细胞高尔基体发生了明显的形态变化。有研究发现血小板无力症患者的血小板高尔基体形态和数量发生了明显的改变。
研究发现,糖尿病、高血压、高同型半胱氨酸血症等病人血清sCD40L水平增高,上述均为脑梗死常见危险因素。正常血小板胞浆内存在合成的CD40L,当血小板活化后由胞内转移至胞膜,在此分裂为可溶性片段释放,而sCD40L与膜结合性CD40L具有相同生物学效应。血中sCD40L约95%来自活化血小板,但目前CD40L由血小板内转移至胞膜并释放的具体途径还不清楚。
目的：
探讨急性脑梗死后血小板高尔基体的形态变化及其意义,以及高尔基体对血小板表达CD40L的作用。
方法：
1、选取20例急性脑梗死患者,分别在发病后第1、7、15天,各采集清晨空腹周围静脉血5ml,收集血小板,选取20位正常成人清晨空腹周围静脉血作对照。通过电镜对血小板超微结构、高尔基体等进行观察。通过免疫电镜的方法,用TGN46作为标记物对高尔基体进行定位观察。各组标本在放大15000倍视野下随机选取10个血小板,对10个血小板内的α颗粒总数进行计数并统计分析。
2、通过流式细胞术测量正常血小板在(静息、活化、先阻断高尔基体功能再活化)三种状态下的CD40L阳性表达率的变化(n=20)。
结果：
1、急性脑梗死后,各时间点血小板内α颗粒均明显减少(P<0.05),以第1天减少较为明显；
2、急性脑梗死后,血小板高尔基体小管和囊泡排列不规整、明显增粗、膨大；
3、免疫电镜试验发现脑梗死后,有α颗粒聚集分布在高尔基体小管和囊泡附近的现象,在发病后15天仍可见到上述变化；
4、高尔基体功能被阻断后,活化血小板表达CD40L明显减少(P<0.05)。
结论：
1急性脑梗死后血小板高尔基体发生明显的形态变化；
2高尔基体的结构改变可能与血小板活化后合成和分泌功能增强有关；
3高尔基体与血小板CD40L的表达有关。
第二部分sCD40L对脑缺血损伤作用的研究
背景：
脑梗死发病率、致残率及病死率均较高,病因复杂。吸烟,高血压、冠心病、高半胱氨酸血症、高脂血症均为脑梗死常见的危险因素,上述患者血中sCD40L明显增高。单纯颈动脉狭窄者血清sCD40L水平也高于正常对照。因此,有学者认为sCD40L可作为预测脑梗死的生物学指标,sCD40L升高与心脑血管疾病发生有关。
sCD40L是CD40L的可溶性形式。sCD40L可与三种受体结合：CD40、α5β1和αⅡbβ3,三者均可表达于血小板。CD40则主要表达于B细胞、活化T细胞、树突状细胞、内皮细胞、单核细胞/巨噬细胞以及中枢神经系统内多种细胞。sCD40L与CD40相互作用不但使脉管系统内产生ROS引起氧化应激,还能诱导人类血管内皮细胞表达粘附分子,并刺激释放趋化因子和细胞因子,上述分子参与动脉粥样硬化斑块的形成。SCD40L与α5β1和αⅡbβ3结合诱导血小板活化。
脑梗死发生后,血脑屏障破坏、白细胞浸润和小胶质细胞增殖活化是导致缺血性脑损伤的主要病理变化。活化的小胶质细胞CD40表达增加,体外研究发现CD40L与CD40相互作用可促进小胶质细胞活化,sCD40L水平升高是否加剧急性脑缺血后神经损伤,目前尚无此方面的研究。
目的：
研究sCD40L对脑缺血损伤的作用,探讨其可能的机制。
方法：
健康雄性SD大鼠(132只)随机分为6个试验组[假手术对照组、术后1d组、术后3d组、术后给药3d组(低剂量rsCD40L)、术后给药3d组(高剂量rsCD40L)、术后5d组](n=22)。参照文献,通过夹闭双侧颈总动脉和低血压的方法制作大鼠急性全脑缺血模型。两个给药组分别在术后第1、2天每日经尾静脉注射rsCD40L一次,参考有关文献,按lμg／kg(低剂量)和l0μg／kg(高剂量)给药,第3天取材。
假手术组于术后第一天处死,其余各组分别于第1d、3d、5d处死,每组大鼠中取4只用于HE染色和免疫组化及免疫荧光实验、6只用于脑组织含水量测定、6只用于血脑屏障通透性检测(在取材前2小时经尾静脉注射伊文斯蓝溶液,取材后检测脑组织中伊文斯蓝含量)、6只用于Western blot检测CD40.ClqA和NF-K Bp65在脑组织的表达情况。术中、术后死亡的动物从试验中剔除,做相应补充。
结果：
1 HE染色观察：
假手术组大脑皮层组织形态结构基本正常。脑缺血后1天组可见部分神经元轻度水肿、胶质细胞增生；3天组可见大量神经元存在核仁不清以及染色质边集的现象、并可见胶质细胞增生：5天组神经胶质细胞增生较明显明显,有嗜神经元现象。给药组可见胶质细胞有所增加、嗜神经元现象增多,以高剂量组改变较为明显。
2脑含水量和血脑屏障通透性结果：
急性脑缺血后脑含水量明显高于假手术组(p<0.05),伊文斯蓝含量也明显高于假手术组(p<0.05),rsCD40L给药组脑含水量和伊文斯蓝含量都显著高于假手术组(p<0.05),高剂量组明显高于低剂量组(p<0.05)。
3免疫组化和免疫荧光：
CD40主要表达于细胞膜,假手术组有少量阳性表达,脑缺血后阳性细胞增多,1天组可见阳性表达最多,5天组有所减少,3天低剂量组阳性表达多于3天组和5天组,3天高剂量组阳性表达明显多于其它各组。ClqA则表达于细胞浆,假手术组只有极少数阳性细胞,1天组表达增多。3天组较1天组表达有所增加,可见内皮细胞也有阳性表达。5天组与1天组表达较少。给药组ClqA阳性细胞明显增加,以高剂量组ClqA阳性细胞表达最多。NF-K Bp65免疫荧光发现,假手术组阳性表达细胞较少,1天组和3天组阳性细胞明显增多,5天组有所减少。给药组表达增加明显,可见NF-KBp65在胞浆和胞核都有表达,高剂量组胞核表达增多。
4 Western blot检测脑组织CD40.ClqA.NF-k Bp65蛋白的表达结果：
在假手术组中CD40少量表达、ClqA.NF-k Bp65有微量表达,1天组3天组和5天组CD40.C1 qA.NF-k Bp65表达均有所增加(p<0.05),CD40和NF-k Bp65表达在第1天时较为明显,3天和5天时二者表达有所减少1天时C1qA表达明显少于CD40和NF-k Bp65表达,在3天时C1qA表达最为显著,表达高峰迟于CD40和NF-k Bp65表达高峰。在给药组中,高剂量组比低剂量组的表达均有显著增加(p<0.05)。
结论：
1脑缺血后sCD40L加剧脑缺血损伤；
2急性脑缺血后CD40.ClqA.NF-K Bp65表达上调可能与sCD40L有关
Change of the Platelet Golgi Apparatus After Ischemic Stroke
Background:
Stroke, a brain attack, is the leading cause of disability and the third leading cause of death. Ischemic stroke is by far the most frequent type of stroke. Until now, platelet activation is thought to be a very important cause of the ischemic stroke. Studies showed that the conglutination and congregation of platelets increased significantly in the whole process of the infarction, the activated platelets synthesized and secreted multiple inflammatory factors. Transient ischemic induced platelet activation and platelet accumulation in the brain microvessels. Blood Platelet structure changed in the patients with stroke acute cerebrovascular infarction.
Golgi complex is an important organ of platelet, for its key role in synthesizing, secretion, and transportation. In our early research, we have found that the structure of neuron golgi complex changed during brain ischemia.
CD40L was transferred onto the membrane after platelet was activated, and then CD40L clipped into sCD40L. After acute ischemia, plasma sCD40L increased significantly. Platelet activation existed in the patients of diabetes, hypertension and Homocysteine(Hcy)with increased sCD40L expression. Almost 95% of sCD40L were from platelets in blood. Until now, the exact way of the CD40L transportation and secretion is not clear.
Purpose:
The aim of this study was to evaluate the structural change of the platelet Golgi apparatus after stroke, and to investigate the potential role of the Golgi apparatus in the expression of platelet CD40L
Methods:
Platelets of 20 patients were observed by electron microscopy and Immuno-electron microscopy with the platelets of 20 healthy volunteers as control. Suspensions of platelets got from 20 healthy volunteers were used to evaluated the role of the Golgi apparatus in the expression of CD40L on platelets by flow cytometry. The expression of CD40L on the activated platelets was observed after the Golgi apparatus was interdicted by the Brefeldin A(BFA) compared with normal platelets and the platelets activated by ADP.
Results:
The Golgi apparatus changed obviously after stroke, the main change was the increasing and widening of the Golgi vesicles and stacks, and there were some a granules around them.αgranules in platelet decreased significantly after stroke(P<0.05). The change remained obviously until the 15th day after stroke. The expression of CD40L on the activated platelets increased significantly compared with normal platelets(P<0.05). Compared with the platelets activated by ADP, the CD40L expression decreased on the platelets which the Golgi apparatus were interdicted by Brefeldin A before activated by ADP(P<0.05).
Conclusions:
The Golgi apparatus may play an important role in the pathophysiology of stroke. The Golgi apparatus may be a potential target for inhibition of CD40L synthesis and transfer in platelet.
The Effect of sCD40L on the Brain ischemic injury
Background:
After acute ischemic stroke, plasma sCD40L increased significantly. Platelet activation exist in patients of diabetes, hypertension, Homocysteine, and sCD40L increased in these patients.95 percent of sCD40L were from platelets in blood. sCD40L is now thought to be a marker to evaluate the severity of stroke. sCD40L increasing is related with the brain vascular disease.
SCD40L is soluble form of the CD40L. sCD40L can bind to three receptors(CD40,α5β1 and aⅡbβ3). All of the three receptors expressed on the platelet. CD40 expressed on B cells, activated T cells, DC, endothelium, monocyte, platelet and also expressed on many kinds of cells in CNS.
Breakage of BBB, leucocyte infiltration and microglia activation are main pathology changes after the onset of stroke. CD40 on the Activated microglia increased. sCD40L can activate microglia. There is no report on the relation of the sCD40L and brain ischemic injury so far.
Purpose:
Study the role of sCD40L in the brain ischemic injury. Investigate the potential mechanisms of sCD40L on the brain ischemic injury.
Methods:
132 SD rats were divided into 6 groups randomly which are control group. 1st day group,3th day group,5th day group, low dose rsCD40L group and high dose rsCD40L group. The control group were executed after one day. the rest groups were executed on the 1st.3th,5th day respectively. The methods of HE stain, immunochemistry, immunofluorescence, and western blot were put in use to observe the expression of the CD40, ClqA, NF-K Bp65 in the brain tissue after ischemia. The brain water content and the EB content in the brain tissue were also observed.
Results:
1 HE
The brain tissues are actually normal in the control group. The neuron death and microglia activation can be observed in the brain ischemic groups. These changes also exist in the 5th day group. The neuron death and microglia activation increased in the rsCD40L groups.
2 Brain water content and EB content
The brain water content and the EB content in the brain tissue increased significantly in the brain ischemic groups compared to the control group(p<0.05). Compared to the brain ischemic groups, a significant increase can also be observed in rsCD40L groups (p<0.05).
3 Immunochemistry and immunofluorescence
CD40 expressed on the membrane, ClqA expressed in the cytoplasm and the NF-kBp65 were observed both in the cytoplasm and nuclear. The expression of the three increased after brain ischemia.
4 Western blot
CD40, ClqA and NF-kBp65 expressed less in brain tissue, while increased at the 1,3,5 day(p<0.05)after brain ischemia. CD40 and NF-xBp65 increased significantly after brain ischemia(p<0.05). ClqA expression significantly increased at 3th day compare to other groups. All the three increased significantly in the high dose rsCD40L group compared to the low dose group (p<0.05).
Conclusions:
1 sCD40L strengthen the brain ischemic injury.
2 sCD40L may strengthen the brain ischemic injury via the activation of the complement and increasing of the inflammation in the ischemic brain tissue.
引文
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