大鼠脑缺血再灌注区ICAM—1的表达与粘附性变化的实验研究

目的:观察大鼠脑缺血再灌注后缺血区ＩＣＡＭ－１ｍＲＮＡ和蛋白的表达及白细胞和血管内皮细胞间粘附性的变化。方法:４０只Ｗｉｓｔａｒ大鼠分为正常组、假手术组和缺血２ｈ再灌注２、４、１２、２４、４８、９６ｈ组,原位杂交和兔疫组化法检测ＩＣＡＭ、１ ｍＲＮＡ和蛋白表达,超高速摄录像系统观察缺血区微血管内白细胞与内皮细胞间的粘附性变化。结果:缺血再灌注后局部脑组织ＩＣＡＭ－１ｍＲＮＡ和蛋白的表达以及微动脉内白细胞与内皮细胞间粘附性均明显增高。结论:脑缺血再灌注后ＩＣＡＭ－１表达增高,介导了白细胞与血管内皮细胞间的粘附增强,参与了缺血再灌注损伤。     

实验性超负荷血糖大鼠脑缺血后脑毛细血管内皮细胞ICAM-1表达的研究

目的　了解超负荷血糖条件下，脑缺血后，脑毛细血管内皮细胞细胞间粘附分子１（ＩＣＡＭ－１）表达的情况。方法　采用ＳＤ大鼠尾静脉注射链脲霉素，建立超负荷血糖模型。用免疫组化方法动态观察大鼠超负荷血糖１ 月条件下以尼龙线栓堵大鼠大脑中动脉造成持续性局灶性脑缺血后不同时间，脑毛细血管内皮细胞ＩＣＡＭ－１ 的表达。结果　超负荷血糖１月脑缺血０．５ 小时ＩＣＡＭ－１ 的表达明显升高；１小时达高峰，表达范围弥漫整个缺血半球；缺血３～１２ 小时， ＩＣＡＭ－１表达仍很明显，但主要集中在颞、顶叶缺血区；缺血２４ 小时表达不明显；假手术组大鼠脑组织毛细血管内皮细胞ＩＣＡＭ－１只有较少的表达；正常血糖对照组及阴性对照者脑毛细血管内皮细胞均未见ＩＣＡＭ－１ 表达。结论　与正常血糖ＳＤ大鼠脑缺血相比，超负荷血糖大鼠脑缺血后， ＩＣＡＭ－１ 在脑毛细血管内皮细胞上表达出现的早而明显，提示对加重脑缺血后的病理损伤起到了重要作用。     

实验性超负荷血糖大鼠脑缺血后脑毛细血管内皮细胞ICAM—1表 …

目的 了解超负荷血糖条件下,脑缺血后,脑毛细血管内皮细胞间粘附分子１（ＩＣＡＭ－１）表达的情况。方法 采用ＳＤ大鼠尾静脉注射链脲霉素,建立超负荷血糖模型。用免疫组化方法动态观察大鼠超负荷血糖１月条件下以尼龙线栓堵大鼠中动脉造成持续性局灶性脑缺血后不同时间,脑毛细血管内皮细胞ＩＣＡＭ－１的表达。结果 超负荷血糖１月脑缺血０．５小时ＩＣＡＭ－１的表达明显升高;１小时达高峰,表达范围弥漫整个缺血半球;缺     

大鼠脑缺血再灌注区ICAM-1表达与白细胞浸润的观察及丹参的影响

目的　观察细胞间粘附分子（ Ｉ Ｃ Ａ Ｍ１） 蛋白在大鼠脑缺血再灌注的不同时程脑组织中的表达与中性白细胞浸润程度的关系及丹参对它们的影响。方法　 Ｓ Ｄ大鼠分为３ 组：假手术组、对照组及丹参组。大脑中动脉缺血２ ｈ 再灌注２ ｈ 、１２ ｈ、２４ ｈ 、４８ ｈ 、７２ ｈ 、７ ｄ、１４ ｄ 后,分别进行 Ｉ Ｃ Ａ Ｍ１ 免疫组织化学及组织 Ｈ Ｅ染色。结果　在脑缺血再灌早期,脑微血管内皮细胞 Ｉ Ｃ Ａ Ｍ１ 免疫反应开始逐渐增加,再灌注４８ ｈ 达到高峰,再灌注１４ ｄ 接近正常水平,同时脑缺血区中性白细胞浸润也随之增加,在时程上与 Ｉ Ｃ Ａ Ｍ１ 表达同步。丹参组,再灌注４８ ｈ 后, Ｉ Ｃ Ａ Ｍ１ 免疫阳性血管数及中性白细胞的浸润比同时间对照组明显降低。结论　脑缺血 Ｉ Ｃ Ａ Ｍ１ 的表达与中性白细胞浸润密切相关,丹参能降低 Ｉ Ｃ Ａ Ｍ１ 的表达,抑制中性白细胞的浸润。     

大鼠局灶性脑缺血再灌注后皮层ICAM-1表达增加

目的：研究大鼠局灶性脑缺血再灌注不同时相皮层 ＩＣＡＭ－１变化规律。方法：改良 Ｋｏｉｚｕｍｉ法建立 ＬＭＣＡＯ局灶性脑缺血再灌注模型;ＲＴ－ＰＣＲ和 Ｄｏｔ ｂｌｏｔｔｉｎｇ法分别检测 ＩＣＡＭ－１的转录和翻译水平变化。结果：缺血皮层 ＩＣＡＭ－１ｍＲＮＡ和 Ｉ－ＣＡＭ－１分别于缺血 ２ｈ和再灌注 ２ｈ显著升高,再灌注 １０和 ４６ｈ达高峰,持续 １周仍维持在较高水平。结论：ＩＣＡＭ－１在脑缺血再灌注时表达明显上调,介导白细胞和脑血管内皮细胞的粘附。ＩＣＡＭ－１ 将成为缺血性脑卒中治疗的新突破点。     

丹参对大鼠脑缺血再灌注损伤保护机制的实验研究

目的进一步了解丹参的神经保护作用是否与它能抑制白细胞的粘附有关。方法ＳＤ大鼠大脑中动脉（ＭＣＡ）栓塞２ｈ再灌注１ｈ后，给予丹参（１５ｇ／ｋｇ，ｉｐ）或同等容量的生理盐水（ＮＳ），用激光多谱勒血流仪及流式细胞仪分别测量给药或ＮＳ后１ｈ、６ｈ、１２ｈ脑缺血区的血流量及１２ｈ外周血中白细胞表面ＣＤ１８、ＣＤ１１ｂ免疫阳性细胞数，在再灌注２４ｈ后行脑组织ＨＥ染色。结果丹参明显增加缺血侧ＭＣＡ分布区血流量，降低外周血中白细胞ＣＤ１８及ＣＤ１１ｂ免疫阳性细胞数，抑制ＭＣＡ缺血区白细胞浸润及神经元的坏死。结论丹参的神经保护作用机制可能与封闭外周血中白细胞粘附分子结合位点，抑制白细胞与血管内皮细胞的粘附有关。     

缺氧复氧对血管内皮细胞ICAM-1表达及内皮-白细胞粘附的影响

目的：评价缺氧／复氧后血管内皮细胞ＩＣＡＭ－１表达及内皮－白细胞粘附率的变化。方法：体外培养大鼠骨髓血窦内皮细胞,缺氧９０ｍｉｎ,分别给予复氧１ｈ,２ｈ,４ｈ,８ｈ,１２ｈ,２４ｈ,用半定量ＥＬＩＳＡ法测ＩＣＡＭ－１的表达量,同时人皮细胞对中性粒细胞的粘附率。     

大鼠局灶性脑缺血再灌注损伤组织病理及超微结构研究

一、材料和方法Ｗ’ｉｓｔａｌ雄性大鼠３６只，体重２７０－３２０９．随机分为缺血１小时再灌注７２／Ｊ’时（Ａ．组）．缺血２小时再灌注７２小时（入组）．缺血３小时再灌注７２小时（Ａ。组），缺血４小时再灌注７２小时（＼组），单纯持续缺血４小时（Ｂ组Ｘ所有大鼠均按Ｋｏｉｚｕｎｕ方法栓塞右侧大脑中动脉：将单股尼龙线的头端０ｓｃｍ热膨胀并打磨后，经颈外动脉，颈总动脉．颈内动脉进人大脑中动脉起始部位．造成栓塞，于栓塞不同时间拔出尼龙线，形成缺血后再灌注。术后大鼠置单箱饲养观察。７２小时后断头取脑，以视交叉为中…     

局灶性脑缺血后脑内髓过氧化物酶活性观察

目的　探讨局灶性脑缺血后脑组织髓过氧化物酶（ＭＰＯ） 活性的测定方法,以及与缺血性损害的关系。方法　采用新型小鼠大脑中动脉线栓模型,检测不同缺血时间组梗塞体积及ＭＰＯ活性。结果　缺血１ ｈ 后再灌注２３ ｈ 组（ｔＭＣＡＯ）缺血灶体积明显小于缺血２４ ｈ 组（ｐＭＣＡＯ）;ＭＰＯ活性在各缺血组缺血侧明显高于对照侧和对照组（ Ｐ＜ ０－０５）,ｐＭＣＡＯ 组缺血侧基底节区ＭＰＯ 活性显著高于ｔＭＣＡＯ 组（ Ｐ＜ ０－０５） ,而两组缺血皮质区ＭＰＯ 活性则无显著差异。结论　本研究建立了局灶性脑缺血的ＭＰＯ活性测定方法,证明ＭＰＯ活性与缺血损伤间具有一定关系。     

TNF-α对血管内皮细胞VCAM-1诱导作用的研究

目的：探讨肿瘤坏死因子－α（ＴＮＦ－α）对血管内皮细胞ＶＣＡＭ－１表达的诱导作用。方法：通过血管内皮细胞培养,采用免疫组织化学方法分别观察不同浓度ＴＮＦ－α（０．２５０Ｕ．ｍＬ＾－１）２４小时内以及相同浓度（１００Ｕｍｌ＾－１）ＴＮＦ－μ０－α０－７２ｈ对内皮细胞ＶＣＡＭ－１表达的影响。结果：与对照组比较,ＴＮＦ－α对内皮细胞ＶＣＡＭ－１的诱导作用具有明显浓度与时间依赖性。结论：ＴＮＦ－α可诱导血     

大鼠脑缺血再灌注模型ICAM-1表达与白细胞浸润关系及亚低温干预治疗的研究

目的　研究大鼠局灶性脑缺血再灌注后不同时程脑组织中的细胞间粘附分子 1 (ICAM 1 )表达规律 ,及其与白细胞浸润的关系 ,并探讨亚低温的治疗作用。方法　采用大鼠大脑中动脉 (MCA)线拴闭塞 /再通法建立大鼠局灶性脑缺血 再灌注模型 ,常温组分别于脑缺血 3小时再灌注 2小时、8小时、2 4小时、48小时、72小时后断头取脑 ;假手术组及亚低温组于脑缺血 3小时再灌注 2 4小时断头取脑 ,行ICAM 1免疫组化及组织HE染色 ,测定ICAM 1表达阳性微血管数及白细胞计数。结果　⑴脑缺血再灌注后 2小时 ,脑缺血的坏死周边区的微血管内皮细胞表达ICAM 1出现增高趋势 ,并于 2 4小时达到高峰 ,各组之间及各组与假手术组间均有显著差异 (均P <0 0 5) ;⑵脑缺血再灌注 8小时出现白细胞浸润 ,且浸润高峰也在 2 4小时 (P <0 0 1 ) ;⑶ICAM 1的表达与白细胞浸润呈正相关 (r =0 .82 7,P <0 0 1 ) ;⑷缺血早期进行亚低温治疗能明显减轻缺血再灌注后ICAM 1的表达及减少白细胞浸润 (P <0 0 1 )。结论　脑缺血再灌注后ICAM 1可介导白细胞和内皮细胞的粘附 ,加速白细胞的浸润 ,提示ICAM 1是造成脑缺血损伤的重要因素之一 ;亚低温的干预治疗能明显减轻缺血再灌注后脑组织病理形态学的损害程度。     

Expression of intercellular adhesion molecule 1 (ICAM-1) is reduced in permanent focal cerebral ischemic mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist

Our previous studies have demonstrated that overexpression of recombinant human interleukin-1 receptor antagonist protein (IL-1ra) via gene transfer can reduce ischemic brain injury. However, the mechanism of action of IL-1ra in ischemia is unclear. Since interleukin-1 can up-regulate intercellular adhesion molecules in endothelium, the present study was designed to determine whether overexpression of the IL-1ra can reduce the expression of intercellular adhesion molecule-1 (ICAM-1) after ischemic injury. Normal saline or adenovirus vector (1x109 particles) encoding the human IL-1ra gene (Ad.RSVIL-1ra) or the Escherichia coli LacZ gene (Ad.RSVlacZ) was injected into the right lateral cerebral ventricle of adult CD-1 mice. After five days, permanent middle cerebral artery occlusion (MCAO) was achieved for 24 h using an intraluminal suture. Cerebral blood flow was monitored by transcranial laser Doppler flowmetry to verify the occlusion. ICAM-1 protein was quantified using Western blot analysis and localized using immunohistochemistry. After MCAO, surface blood flow in the ischemic hemisphere was decreased to 9-11% of the baseline. There were fewer ICAM-1 positive vessels in the ischemic cortex of the Ad.RSVIL-1ra transfected mice than in the Ad.RSVlacZ transfected and saline treated mice (138+/-19 vs. 249+/-25, 284+/-22, p<0.05). Western blot analysis shows that ICAM-1 protein decreased 50-60% in the Ad. RSVIL-1ra group compared to the other two groups. There were no significant differences in the numbers of positive vessels in the ischemic basal ganglia and contralateral hemisphere among the three groups. Our studies suggest that IL-1ra overexpression can down-regulate the expression of ICAM-1 in the ipsilateral cortex in ischemic mice. Interleukin-1 may play an important role in the activation of inflammatory reaction during focal cerebral ischemia by promoting leukocyte adhesion on the endothelium cells.     

腺病毒介导IL—1ra基因对小鼠局灶性脑缺血模型中ICAM—1表达抑制作用

目的 IL－1可诱导内皮细胞粘附分子表达,促进缺血部位炎症和局部细胞损伤,应用腺病毒介导IL－1ra基因观察其对小鼠局灶性脑缺血后内皮细胞ICAM－1蛋白表达的抑制作用。方法 构建携带外源性基因,复制缺陷的人腺病毒,并将其作为载体介导IL－1lra基因,Ecoli LacZ基因或以生理盐水分别注射于成年CD－1小鼠右侧脑室,5d后,对实验小鼠分别进行脑血管腔内栓塞术,造成持续性中动脉栓塞,缺血程度由激光多普勒流量仪确定,采用组织病理切片观察病灶部位白细胞浸润和炎症反应现象,免疫组化染色测定血管内皮细胞ICAM－1蛋白表达和用Western印迹进行定量分析。结果 病灶侧皮质区血管内皮细胞ICAM－1蛋白表达量在IL－1ra基因组有明显下降且局部炎症反应轻微,与LacZ基因组和生理盐水组比较差异有显著性。ICAM－1蛋白定量分析表明,前组比后两组下降50％左右。但正常侧和病灶侧的脑基质神经节区无明显差异,结论 IL－1ra定量分析表明,前组比后两组下降50％左右,但正常侧和病灶侧的脑基质神经节区无明显差异,结论 IL－1ra基因表达蛋白通过抑制IL－1的生物学功能,明显下调脑缺血皮质区ICAM－1蛋白表达,有助于减轻局部炎症。     

C3a receptor modulation of granulocyte infiltration after murine focal cerebral ischemia is reperfusion dependent.

The complement anaphylatoxin C3a contributes to injury after cerebral ischemia in mice. This study assesses the effect of C3a receptor antagonist (C3aRA) on leukocyte infiltration into the ischemic zone. Transient or permanent middle cerebral artery occlusion (MCAO) was induced in wild-type C57Bl/6 mice. Intraperitoneal C3aRA or vehicle was administered 45 mins before or 1 h after occlusion. Twenty-four hours after occlusion, we harvested brain tissue and purified inflammatory cells using flow cytometry. Soluble intercellular adhesion molecule (ICAM)-1 protein levels were assessed using enzyme-linked immunosorbent assays, and ICAM-1 and C3a receptor (C3aR) expression was confirmed via immunohistochemistry. In the transient MCAO model, animals receiving C3aRA showed smaller strokes, less upregulation of C3aR-positive granulocytes, and less ICAM-1 protein on endothelial cells than vehicle-treated animals; no significant differences in other inflammatory cell populations were observed. C3a receptor antagonist-treated and vehicle-treated animals showed no differences in stroke volume or inflammatory cell populations after permanent MCAO. These data suggest that blocking the binding of C3a to C3aR modulates tissue injury in reperfused stroke by inhibiting the recruitment of neutrophils to the ischemic zone. It further establishes antagonism of the C3a anaphylatoxin as a promising strategy for ameliorating injury after ischemia/reperfusion.     

亚低温对大鼠局灶性脑缺血ICAM-1和TNF-α表达的影响

目的:脑缺血后ICAM-1和TNF-α的表达增加。降低ICAM-1和TNF-α的表达和亚低温对缺血性脑卒中具有神经保护作用。本研究的目的在于观察亚低温对大鼠局灶性脑缺血ICAM-1和TNF-α表达的影响,并探讨亚低温对脑缺血性损害的神经保护作用机制。方法:采用栓线法阻断大鼠一侧大脑中动脉制作局灶性脑缺血动物模型,设实验组和对照组,分别置于冰毯机上和常温操作台上,使其肛温分别保持在34℃±0.5℃和37℃±0.5℃。12h后断头取脑,采用免疫组化方法检测缺血区ICAM-1阳性血管数目和采用双抗夹心酶联免疫吸附法(ELISA)测定血清TNF-α水平。结果:实验组ICAM-1和TNF-α的表达较对照组下降。结论:亚低温可降低大鼠局灶性脑缺血的ICAM-1和TNF-α的表达,推测亚低温降低ICAM-1和TNF-α的表达为亚低温减轻脑缺血性损害的神经保护作用机制之一。     

Inhibition of calcium/calmodulin‐dependent protein kinase kinase (CaMKK) exacerbates impairment of endothelial cell and blood–brain barrier after stroke

Brain microvascular endothelial cells play an essential role in maintaining blood–brain barrier (BBB) integrity, and disruption of the BBB aggravates the ischemic injury. CaMKK (α and β) is a major kinase activated by elevated intracellular calcium. Previously, we demonstrated that inhibition of CaMKK exacerbated outcomes, conversely, overexpression reduced brain injury after stroke in mice. Interestingly, CaMKK has been shown to activate a key endothelial protector, sirtuin 1 (SIRT1). We hypothesized that CaMKK protects brain endothelial cells via SIRT1 activation after stroke. In this study, Oxygen‐Glucose Deprivation (OGD) was performed in human brain microvascular endothelial cells. Stroke was induced by middle cerebral artery occlusion (MCAO) in male mice. Knockdown of CaMKK β using siRNA increased cell death following OGD. Inhibition of CaMKK β by STO‐609 significantly and selectively down‐regulated levels of phosphorylated SIRT1 after OGD. Changes in the downstream targets of SIRT1 were observed following STO‐609 treatment. The effect of STO‐609 on cell viability after OGD was absent, when SIRT1 was concurrently inhibited. We also demonstrated that STO‐609 increased endothelial expression of the pro‐inflammatory proteins ICAM‐1 and VCAM‐1 and inhibition of CaMKK exacerbated OGD‐induced leukocyte‐endothelial adhesion. Finally, intracerebroventricular injection of STO‐609 exacerbated endothelial apoptosis and reduced BBB integrity after 24‐hr reperfusion following MCAO in vivo. Collectively, these results demonstrated that CaMKK inhibition reduced endothelial cell viability, exacerbated inflammatory responses and aggravated BBB impairment after ischemia. CaMKK activation may attenuate ischemic brain injury via protection of the microvascular system and a reduction in the infiltration of pro‐inflammatory factors.     

Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1beta converting enzyme deficient mice.

Interleukin-1beta (IL-1beta) is expressed after cerebral ischemia and blocking its action reduces subsequent ischemic brain injury. However, the mechanisms by which IL-1beta affects ischemic brain are not understood. To investigate the role of IL- 1beta in regulation of tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) during focal cerebral ischemia, the authors studied mutant mice deficient in the IL-1 converting enzyme (ICE) gene (ICE knockout [KO] mice). Ninety-four adult male ICE KO and wild-type mice underwent 3, 6, 12, and 24 hours of permanent middle cerebral artery occlusion using the suture method. Expression of TNF-alpha and ICAM-1 protein in ischemic brain was examined using immunohistochemistry and Western blot analysis. Neither ICE KO nor wild-type mice had significant differences in CBF and body temperature measurements during the ischemic procedure. TNF-alpha expression increased in the ipsilateral hemisphere after 3 hours of occlusion, peaked at 12 hours and decreased at 24 hours of ischemia in both ICE KO and wild-type mice. ICAM-1 immunohistochemistry showed that the number of ICAM-1-positive vessels in the ischemic hemisphere was reduced in ICE KO mice (P < .05). Western blot analysis showed that ICAM-1 protein expression was significantly attenuated in the ipsilateral hemisphere in the ICE KO mice, which paralleled the immunohistochemistry results. The authors' results indicate that TNF-alpha expression is increased in both ICE KO and wild-type mice suggesting that TNF-alpha expression is not related to or upregulated by IL-1beta . ICAM-1 expression is significantly reduced in the ICE KO mice suggesting that IL-1beta plays an important role in the upregulation of adhesion molecules during focal cerebral ischemia.     

Early NFkappaB activation is inhibited during focal cerebral ischemia in interleukin-1beta-converting enzyme deficient mice

Our previous study demonstrated that the inhibition of interleukin-1beta (IL-1beta) reduces ischemic brain injury; however, the molecular mechanism of the action of IL-1 in cerebral ischemia is unclear. We are investigating currently the role of NFkappaB during focal cerebral ischemia, using mutant mice deficient in the interleukin-1 converting enzyme gene (ICE KO) in a middle cerebral artery occlusion (MCAO) model. Adult male ICE KO and wild-type mice (n = 120) underwent up to 24 hr of permanent MCAO. Cytoplasmic phospho-NFkappaB/p65 expression in ischemic brain was examined using Western blot analysis and immunohistochemistry. NFkappaB DNA-binding activity was detected using electrophoretic mobility shift assay (EMSA). Furthermore, ICAM-1 expression was examined in both the ICE KO and wild-type mice (WT). Western blot analysis and immunostaining showed that the level of cytosolic phosphorylated NFkappaB/p65 increased after 2 and 4 hr of MCAO in WT mice; however, NFkappaB/p65 was significantly reduced after MCAO in the ICE KO mice (P < 0.05). EMSA showed that NFkappaB DNA-binding activity increased after MCAO in WT mice; but this effect was reduced in the ICE KO mice. The number of ICAM-1-positive vessels in the ischemic hemisphere was greatly attenuated in the ICE KO mice (P < 0.05), which paralleled the results of immunohistochemistry. Our results demonstrate that NFkappaB phosphorylation is reduced in ICE KO mice, suggesting that ICE or IL-1 are involved in early NFkappaB phosphorylation. Because cerebral ischemia induced infarction is significantly reduced in ICE KO mice, we conclude that early NFkappaB phosphorylation plays a disruptive role in the ischemic process.     

血红素氧合酶-1及血红素氧合酶-2在大鼠局灶性脑缺血中的意义

目的　研究血红素氧合酶 1(HO 1)及血红素氧合酶 2 (HO 2 )在局灶性脑缺血中的作用。方法　采用大鼠大脑中动脉栓塞脑缺血模型 ,对 6 6只大鼠脑缺血后不同时间点进行HO 1、HO 2免疫组化染色及病理学研究 ,并用计算机图像分析技术计算两者表达水平。结果　栓塞后 30min大鼠皮质及海马即有HO 1阳性神经元及胶质细胞的表达 ,且随着时间推移HO 1的表达逐渐增强 ,到栓塞后 12h达峰值 (P <0 0 1) ,以后逐渐下降 ,栓塞后 1周仍有HO 1表达。HO 2在正常大鼠及梗死大鼠脑组织内均有表达。栓塞后不同时间段 ,HO 2阳性神经元的数量无明显变化 (P >0 0 5 ) ,但HO 2表达呈动态变化 ,2 4h时最高 (P <0 0 1) ,以后逐渐下降。结论　脑缺血时脑内HO 1、HO 2表达的不同变化 ,是脑组织对损伤恢复重要的机制之一。HO 1修复受损的神经元和胶质细胞 ,而HO 2在于维护正常细胞的稳定