CB1 Cannabinoid Receptor-Dependent and -Independent Inhibition of Depolarization-Induced Calcium Influx in Oiigodendrocytes

Ca2+稳态平衡的调节在少突胶质细胞功能和存活中起重要作用.大麻素CB1和CB2受体在许多细胞中调节Ca2+水平和/或K+电流.本文利用培养的少突胶质细胞中,通过增高细胞外K+浓度(50 mM诱导膜去极化,研究大麻素复合物在此过程引发钙内流中的作用.CB2受体激动剂ACEA导致去极化诱导的少突胶质细胞胞浆的Ca2+瞬变表达浓度依赖性抑制,最大效应为(94±3)%,半效应浓度(EC50)为(1.3±0.03)μM.这种作用可被CB2/CB2激动剂CP55、940、内源性大麻素类AEA和2-AG所模拟,但是CB2受体选择性激动剂JWH133没有作用.CB2受体拮抗剂AM251(1μM)也可减少细胞外高K+诱导的Ca2+反应.但不能防止ACEA(3 μM)诱发的抑制效应.然而,ACEA和AEA减少去极化诱导的Ca2+瞬变的能力在CB2受体敲除小鼠和经百日咳毒素预处理的少突胶质细胞中明显降低.内流性K2+通道阻断剂BaCI:(300 μM)和CsCl2(1 mM)降低电压诱导的Ca2+内流并部分阻断ACEA的抑制效应.本文表明,大麻素抑制少突胶质细胞中去极化诱导的Ca2+瞬变是通过包括PTX-敏感的Gi/o蛋白和阻断K2+内流通道的CB2受体依赖性和非依赖性机制.     

Oligodendrocytes in Mouse Corpus Callosum are Coupled Via Gap Junction Channels Formed by Connexin47 and Connexin32

已有的超微结构研究显示,白质中的少突胶质细胞和星形胶质细胞之间存在缝隙连接,但少突胶质细胞之间不存在缝隙连接,虽然体外培养的少突胶质细胞可形成功能性缝隙连接。本文研究新生小鼠胼胝体急性脑片中的少突胶质细胞的功能性连接。以全细胞膜片钳技术用生物胞素(一种可渗透的缝隙连接示踪剂)标记少突胶质细胞。平均61个细胞为链霉亲和素-Cy3标记的生物胞素阳性。约77%的连结细胞表达少突胶质细胞标志蛋白CNPase阳性染色,9%表达星形胶质细胞标志蛋白GFAP阳性,14%为CNPase和GFAP阴性。后者的大部分表达Olig2和一些NG2(少突胶质细胞前体细胞的标志物)。少突胶质细胞表达Cx47、Cx32和Cx29,星形胶质细胞表达Cx43和Cx30。在Cx47敲除小鼠中,连结细胞的数量减少80%。单独删除Cx32或Cx29并不能显著减少连结细胞的数量,但Cx32/Cx47双缺陷小鼠中没有观察到相互连结的细胞。Cx47敲除完全消除了少突胶质细胞与星形胶质细胞间的耦联。在Cx43敲除动物中,少突胶质细胞-星形胶质细胞间连接仍然存在,但与少突胶质细胞前体细胞间的耦联没有被观察到。在Cx43/Cx30双敲除小鼠中,少突胶质细胞-星形胶质细胞连接几乎不存在。解开连结的少突胶质细胞显示为较高的膜输入电阻。本文认为,白质中的少突胶质细胞依靠Cx47和Cx32的表达形成功能性的合胞体,而星形胶质蛋白缝隙连接蛋白的表达能提升此网络的大小。     

Role of CB1 and CB2 cannabinoid receptors in the development of joint pain induced by monosodium iodoacetate

Joint pain is a common clinical problem for which both inflammatory and degenerative joint diseases are major causes. The purpose of this study was to investigate the role of CB1 and CB2 cannabinoid receptors in the behavioral, histological, and neurochemical alterations associated with joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for CB1 (CB1KO) and CB2 cannabinoid receptors (CB2KO) and transgenic mice overexpressing CB2 receptors (CB2xP). In addition, we evaluated the changes induced by MIA in gene expression of CB1 and CB2 cannabinoid receptors and μ-, δ- and κ-opioid receptors in the lumbar spinal cord of these mice. Wild-type mice, as well as CB1KO, CB2KO, and CB2xP mice, developed mechanical allodynia in the ipsilateral paw after MIA intra-articular injection. CB1KO and CB2KO demonstrated similar levels of mechanical allodynia of that observed in wild-type mice in the ipsilateral paw, whereas allodynia was significantly attenuated in CB2xP. Interestingly, CB2KO displayed a contralateral mirror image of pain developing mechanical allodynia also in the contralateral paw. All mouse lines developed similar histological changes after MIA intra-articular injection. Nevertheless, MIA intra-articular injection produced specific changes in the expression of cannabinoid and opioid receptor genes in lumbar spinal cord sections that were further modulated by the genetic alteration of the cannabinoid receptor system. These results revealed that CB2 receptor plays a predominant role in the control of joint pain manifestations and is involved in the adaptive changes induced in the opioid system under this pain state.     

异丙酚对内毒素血症鼠肺系数及钙离子影响研究

目的观察异丙酚对内毒素血症鼠肺组织PaO2、肺系数及钙离子浓度的影响。方法72只Waster雄性大鼠分为3组,对照组(C组)、内毒素组(L组)和异丙酚 内毒素组(P组)。L组在腹腔内缓慢注入内毒素;P组在皮下缓慢注入异丙酚后再注入内毒素。分别在注射后30、90、1803、60min时处死动物,取出肺组织,测定肺系数、钙离子含量及病理切片检查。结果L组在注入内毒素后各时点PaO2下降,肺系数和钙离子浓度显著增高(P<0.05)。P组与L组相比显著减轻PaO2下降,降低肺系数和钙离子浓度(P<0.05)。结论异丙酚可降低内毒素血症鼠肺组织钙离子浓度,对肺组织有保护作用。     

The emerging role of cannabinoid neuromodulators in symptom management

INTRODUCTION: The cannabinoids nabilone (Cesamet) and dronabinol (Marinol) are indicated for the management of chemotherapy-induced nausea and vomiting (CINV) in cancer patients who have failed to respond adequately to conventional antiemetic therapy. DISCUSSION: The endocannabinoid (CB) system interacts with numerous other systems and pharmaceutical cannabinoids target ubiquitous CB1 and CB2 receptors in the central nervous system and periphery, relieving nausea and vomiting and pain. SUMMARY: The benefits of this novel class of medications in cancer may extend beyond CINV, as indicated by data from preclinical studies and animal models.     

脑血栓形成急性期患者血小板静息及激活状态胞浆游离钙离子浓度钙调素含量的实验研究

目的探讨血小板静息状态胞浆游离钙离子浓度([Ca2 ]i)、激活状态胞浆游离钙离子浓度([Ca2 ]ic)、钙调素含量 (CaM)在脑血栓形成(CT)急性期的变化及其作用。方法应用Fura-2荧光标记示踪法及酶联免疫法(ELISA)测定了31例CT急性期患者血小板[Ca2 ]i、[Ca2 ]ic浓度和CaM含量。结果脑血栓形成急性期患者血小板[Ca2 ]i、[Ca2 ]ic、CaM含量分别为(152．25 ±30．57)nmol／L,(200．36±33．62)nmol／L,(441．67±209．31)fg／102个血小板;正常对照组含量分别为(111．31±21．85)nmol／L, (158．43±22．44)nmol／L,(301．88 ±218．10)fg／102个血小板,脑血栓形成急性期患者血小板[Ca2 ]i、[Ca2 ]ic、CaM含量均明显高于正常对照(P<0．01,P<0．05)。结论脑血栓形成急性期患者,应用钙拮抗剂降低血小板胞浆钙离子浓度,可抑制血小板功能。     

电压依赖性钙通道参与大振幅微小兴奋性突触后电流形成的实验研究

目的观察电压依赖性钙通道是否作用于大鼠脊髓背角胶状质层(SG)神经元大振幅微小兴奋性突触后电流的形成。方法选用成年雄性Sprague-Dawley(SD)大鼠,2%～3%异氟烷麻醉后,分离其腰骶部的脊髓,然后切片。采用全细胞电压钳技术,玻璃微电极的电阻为4～6 MΩ,钳制电压为70 mV,记录胶状质层神经元微小兴奋性突触后电流(mEPSC)电流。将电流信号用Axopatch 200来放大并储存于电脑。对照组和用药结束后,持续采样mEPSC电流30 s。mEPSC电流的频率和振幅用Clampfit 8.1进行分析。结果钳制电压为70 mV时,所有SG神经元均有自发性的EPSC。辣椒素增加mEPSC发生的频率和波幅。钴离子抑制辣椒素诱导的大振幅mEPSC。钴离子抑制辣椒素诱导的mEPSC的平均振幅,而不抑制其发生频率。结论电压依赖性钙离子通道参与了辣椒素引起的痛觉形成。     

Hemodynamic Effects of Intravenous Fat Emulsion in an Animal Model of Severe Verapamil Toxicity Resuscitated with Atropine, Calcium, and Saline

Background
Intravenous fat emulsion (IFE) decreases cardiotoxicity from several lipid-soluble drugs, including verapamil.
Objectives
To verify if the addition of IFE to the standard treatment of severe verapamil toxicity would improve hemodynamics and survival.
Methods
Fourteen dogs were instrumented to measure systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), heart rate, cardiac output, central venous pressures, left ventricular pressure changes over time, mixed venous oxygen saturation, pH, and base excess. Verapamil toxicity, defined as a 50% decrease in MAP, was induced with verapamil at 6 mg/kg/hr and maintained for 30 minutes by titrating the verapamil infusion rate. Following verapamil toxicity, the verapamil infusion rate was changed to 2 mg/kg/hr and continued for 90 minutes. All dogs were resuscitated with atropine (0.04 mg/kg intravenously) and calcium chloride (15 mg/kg intravenously every 5 minutes for three doses) and then randomized to receive either IFE (7 mg/kg of 20%) intravenously or equivalent volumes of 0.9% normal saline over 30 minutes. Measurements were recorded for 120 minutes by investigators blinded to the treatment. Data were analyzed using analysis of variance, survival analysis, and log-rank test.
Results
Before the 30-minute IFE or normal saline infusion, there were no differences in hemodynamic parameters. After IFE or normal saline infusion, the IFE-treated group had higher MAP at 30 minutes (95% confidence interval [CI] = 5.6 to 44.7 mm Hg), 45 minutes (95% CI = 10.8 to 50.0 mm Hg), and 60 minutes (95% CI = 10.2 to 53.1 mm Hg). Kaplan–Meier 120-minute survival rate was 14% (95% CI = 0.5% to 53%) for the saline group as compared with 100% (95% CI = 59% to 100%) for the IFE group (p = 0.01).
Conclusions
Standard resuscitation and IFE increase MAP and survival in an animal model of severe verapamil toxicity compared with standard resuscitation alone.     

丙酮酸钙对小鼠力竭运动后抗氧化损伤作用的机制

目的：探讨补充3周丙酮酸钙对于小鼠力竭后组织损伤的保护作用机制。方法：雄性小鼠40只,随机分为安静对照组（C组）、运动对照组（Ec组）、丙酮酸钙组（P组）、运动丙酮酸钙组（Ep组）各10只,C及Ec组小鼠每天灌服10%阿拉伯胶溶液,P及Ep组每天给予600mg/kg的丙酮酸钙灌胃,共3周。3周末时各组大鼠均进行力竭运动实验,检测肝脏组织中过氧化氢（H2O2）和谷胱甘肽（GSH）的含量、ATP酶活力。结果：与Ec组比较,Ep组小鼠运动至力竭时间明显延长,运动能力显著提高（106.9±24.7min、167.0±31.2min,P〈0.01）。Ep组GSH含量明显高于其它各组（P〈0.05）。运动力竭后Ec组和Ep组H2O2含量明显高于C、P组,Ep组低于Ec组（P〈0.01）。结论：补充丙酮酸钙能明显提高小鼠力竭运动能力和抗氧化损伤能力,其可能原因是提高GSH抗氧化能力及抵抗部分ATP酶的失活。     

Electroacupuncture Increases CB2 Receptor Expression on Keratinocytes and Infiltrating Inflammatory Cells in Inflamed Skin Tissues of Rats

Endogenous cannabinoids and peripheral cannabinoid CB2 receptors (CB2Rs) are involved in the antinociceptive effect of electroacupuncture (EA) on inflammatory pain. However, it remains unclear about how EA affects the expression and distribution patterns of peripheral CB2Rs in inflamed skin tissues. To study this, inflammatory pain was induced by local injection of complete Freund's adjuvant into the hindpaw of rats. The mRNA and protein levels of CB2Rs were quantified by using RTPCR and Western blotting, respectively. The distribution of CB2Rs on keratinocytes and immune cells recruited to the inflamed skin tissues was determined by using double-immunofluorescence labeling. Induction of tissue inflammation significantly increased the mRNA and protein levels of CB2Rs in the skin tissue. Also, both 2 Hz and 100 Hz EA, applied to GB30 and GB34, significantly increased the mRNA and protein levels of CB2Rs in inflamed tissues compared to the sham EA group. CB2Rimmunoreactivities were mainly distributed in keratinocytes, macrophages, and T-lymphocytes in the epidermis and dermis of the inflamed skin tissue. Inflammation caused a significant increase in the number of CB2R-immunoreactive keratinocytes, macrophages, and T-lymphocytes. Furthermore, compared to the sham EA group, EA at 2 or 100 Hz significantly increased the number of keratinocytes, macrophages, and T-lymphocytes with CB2R-immunoreactivity in the inflamed skin tissue. Therefore, our findings suggest that EA is associated with upregulation of local CB2Rs in the inflamed skin tissue. EA primarily potentiates the expression of CB2Rs on keratinocytes and infiltrating inflammatory cells at the site of inflammation.     

补充丙酮酸钙对抵抗小鼠急性运动性肝损伤的保护机制

目的:探究补充丙酮酸钙对小鼠肝脏抗氧化损伤的作用机制。方法:雄性小鼠32只,随机分为安静对照组(C组)、运动对照组(Ec组)、丙酮酸钙组(P组)、运动丙酮酸钙组(Ep组)各8只。P组、Ep组小鼠每天给予600mg/kg.d的丙酮酸钙灌胃;C组、Ec组给予同等剂量蒸馏水灌胃。3周末时Ec组和Ep组大鼠进行力竭运动实验。检测各组肝脏组织中一氧化氮(NO)、一氧化氮合酶(TNOS,iNOS)及肝线粒体中的钙(Ca2+)浓度。结果:与C组比较,Ec组及Ep组小鼠肝脏组织TNOS、iNOS及NO、线粒体Ca2+的浓度均明显上升(P0.05,0.01);Ep组明显低于Ec组(P0.05,0.01);P组与C组比较,各项指标均无统计学意义。结论:补充3周的丙酮酸钙能明显降低急性运动性肝损伤NO和线粒体Ca2+浓度,对预防和治疗运动性急慢性肝病有指导意义。     

补充丙酮酸钙对急性力竭运动小鼠心肌损伤的保护机制

目的：观察补充丙酮酸钙对小鼠心脏一氧化氮（NO）及NO合酶（NO-NOS）体系及线粒体Ca2＋的影响。方法：雄性小鼠32只,随机分为安静对照组（C组）、运动对照组（Ec组）、丙酮酸钙组（P组）、运动丙酮酸钙组（Ep组）各8只。P组、Ep组小鼠每天给予600 mg/kg.d的丙酮酸钙灌胃;C组、Ec组给予同等剂量蒸馏水灌胃。3周末时Ec组和Ep组小鼠进行力竭运动实验1次后,将4组小鼠处死。检测各组心脏组织中NO、TNOS,iNOS及心脏线粒体中的Ca2＋浓度。结果：与C组比较,Ec组及Ep组小鼠心脏组织TNOSi、NOS及NO、线粒体Ca2＋的浓度均明显上升（P〈0.05,0.01）;Ep组明显低于Ec组（P〈0.05）;P组与C组比较,各项指标均无统计学意义。结论：补充3周的丙酮酸钙能明显降低急性运动引起的心肌NO和线粒体Ca2＋浓度。为补充丙酮酸钙对心肌运动损伤的保护作用机制提供一定的实验依据。     

肿瘤相关钙信号传导蛋白-2基因mRNA在人胰腺癌组织中表达的临床意义

目的:探讨人胰腺癌肿瘤相关钙信号传导蛋白-2( tumor-associated calcium signal transducer-2,TROP-2)基因在胰腺癌组织中表达及其临床意义.方法:提取56例人胰腺癌及癌旁正常组织中总mRNA,采用实时荧光定量逆转录聚酶链反应(RT-PCR)法检测其中TROP-2 mRNA表达情况;并分析其表达与患者年龄、肿瘤大小、淋巴结转移、肿瘤分化程度和TNM分期相关性.结果:以2-△△Ct≥2为阳性标准,TROP-2在胰腺癌组织中阳性表达率为75.0％ (42/56),而癌旁正常组织未见TROP-2 mRNA表达,两者差异有统计学意义(P＜0.001).TROP-2 mRNA过表达与肿瘤大小、淋巴结转移、TNM分期显著相关(均P＜0.01),而与患者年龄和肿瘤分化程度无关(均P＞0.05).结论:TROP-2基因表达与胰腺癌进展密切相关,可能是反映胰腺癌侵袭、转移的重要指标之一.     

The role of endocannabinoids in pain modulation

The endocannabinoid system (ES) is comprised of cannabinoid (CB) receptors, their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism. Endocannabinoids serve as retrograde signaling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, that interact with other neurotransmitters. Physiological stimuli and pathological conditions lead to differential increases in brain endocannabinoids that regulate distinct biological functions. Furthermore, endocannabinoids modulate neuronal, glial, and endothelial cell function and exert neuromodulatory, anti‐excitotoxic, anti‐inflammatory, and vasodilatory effects. Analgesia is one of the principal therapeutic targets of cannabinoids. Cannabinoid analgesia is based on the suppression of spinal and thalamic nociceptive neurons, but peripheral sites of action have also been identified. The chronic pain that occasionally follows peripheral nerve injury differs fundamentally from inflammatory pain and is an area of considerable unmet therapeutic need. Over the last years, considerable progress has been made in understanding the role of the ES in the modulation of pain. Endocannabinoids have been shown to behave as analgesics in models of both acute nociception and clinical pain such as inflammation and painful neuropathy. The framework for such analgesic effects exists in the CB receptors, which are found in areas of the nervous system important for pain processing and in immune cells that regulate the neuro‐immune interactions that mediate the inflammatory hyperalgesia. The purpose of this review is to present the available research and clinical data, up to date, regarding the ES and its role in pain modulation, as well as its possible therapeutic perspectives.     

钙拮抗剂对重症急性胰腺炎肾损害保护作用的实验研究

【目的】探讨钙拮抗剂对重症急性胰腺炎（SAP）大鼠肾损害的影响。【方法】Wistar大鼠45只,随机分为假手术组（A组）、SAP组（B组）和钙拮抗剂治疗组（C组）,观察各组动物肾功能、炎性细胞因子IL-1、IL-6、TNF-α和肾脏组织病理学改变。【结果】SAP时血清中炎性细胞因子IL-1、IL-6、TNF-α升高,肾功能下降,肾组织损害严重。钙拮抗剂治疗组炎性因子水平降低,肾组织损害减轻,肾功能明显改善。【结论】钙拮抗剂可抑制SAP某些细胞因子的产生和释放,对肾损害具有保护作用。     

Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states

Spinal cord injury (SCI) commonly results in the development of neuropathic pain, which can dramatically impair the quality of life for SCI patients. SCI-induced neuropathic pain can be manifested as both tactile allodynia (a painful sensation to a non-noxious stimulus) and hyperalgesia (an enhanced sensation to a painful stimulus). The mechanisms underlying these pain states are poorly understood. Clinical studies have shown that gabapentin, a drug that binds to the voltage-gated calcium channel alpha-2-delta-1 subunit (Ca_vα2δ-1) proteins is effective in the management of SCI-induced neuropathic pain. Accordingly, we hypothesized that tactile allodynia post SCI is mediated by an upregulation of Ca_vα2δ-1 in dorsal spinal cord. To test this hypothesis, we examined whether SCI-induced dysregulation of spinal Ca_vα2δ-1 plays a contributory role in below-level allodynia development in a rat spinal T9 contusion injury model. We found that Ca_vα2δ-1 expression levels were significantly increased in L4-6 dorsal, but not ventral, spinal cord of SCI rats that correlated with tactile allodynia development in the hind paw plantar surface. Furthermore, both intrathecal gabapentin treatment and blocking SCI-induced Ca_vα2δ-1 protein upregulation by intrathecal Ca_vα2δ-1 antisense oligodeoxynucleotides could reverse tactile allodynia in SCI rats. These findings support that SCI-induced Ca_vα2δ-1 upregulation in spinal dorsal horn is a key component in mediating below-level neuropathic pain states, and selectively targeting this pathway may provide effective pain relief for SCI patients.     

Inhibition of localized thrombosis in P2Y1-deficient mice and rodents treated with MRS2179, a P2Y1 receptor antagonist

Summary.  Previous studies in experimental models revealed a role for the P2Y₁ platelet ADP receptor in systemic vascular thromboembolism models. In the present work, we used models of localized arterial and venous thrombosis to assess the role of the P2Y₁ receptor in these processes. Arterial thrombosis was induced in one mesenteric arteriole of a mouse using FeCl₃, while venous thrombosis was studied in a Wessler model adapted to rats. P2Y₁-deficient mice and mice treated with the P2Y₁ antagonist MRS2179 displayed significantly less arterial thrombosis than their respective controls. Combination of P2Y₁ deficiency with P2Y₁₂ inhibition led to a significant additive effect. Venous thrombosis was slightly but significantly inhibited in MRS2179-treated rats. These results demonstrate a role for the P2Y₁ receptor in both arterial and venous thrombosis, further establishing this receptor as a potential target for antithrombotic drugs.     

Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4

BACKGROUND: Migrainous vertigo (MV) is increasingly recognized as a common cause of episodic vertigo. MV displays several clinical similarities with familial hemiplegic migraine (FHM) and episodic ataxia type 2 (EA-2), which have been linked to mutations in 3 genes, CACNA1A, encoding a neuronal calcium channel alpha subunit, ATP1A2, encoding a catalytic subunit of a Na(+)/K(+)-ATPase, and most recently the voltage-gated sodium channel SCN1A. The present study explored the hypothesis that mutations in CACNA1A, ATP1A2, SCN1A, and the calcium channel beta(4) subunit CACNB4 confer susceptibility to MV. METHODS: Mutation analysis of the coding exons and exon/intron junctions of CACNA1A, ATP1A2, SCN1A, and CACNB4 was performed in 14 unrelated MV patients by conformation sensitive gel electrophoresis and automated sequence analysis. RESULTS: Analysis of the 4 candidate genes in the 14 MV patients resulted in the identification of a total of 26 sequence variants. The silent substitution D29D in CACNB4 was observed in 2 MV patients and was not present in 46 ethnically matched control DNA samples. The remaining variants were also observed in control DNA samples and the allele frequencies of variants that resulted in amino acid substitutions were not significantly different between patients and controls. CONCLUSIONS: Based on this group of patients there is no evidence that the genes causing FHM and EA-2 represent major susceptibility loci for MV.     

电针对脑缺血大鼠VEGF及Flk-1表达和细胞外钙离子浓度的影响

目的 :观察电针对急性脑缺血大鼠血管新生和细胞外钙离子浓度的影响。方法 :33只雄性Wistar大鼠随机分成正常组、模型组和电针组各 11只。复制急性大脑中动脉缺血模型 ,电针组针刺百会和水沟穴 ,每天 1次 ,共 6次 ,免疫组织化学方法观察血管内皮生长因子 (VEGF)及其受体Flk 1的表达 ;采用中医传感针测定脑组织细胞外钙离子的浓度。结果 :模型组梗死灶周围VEGF和Flk 1表达增强 (P <0 .0 5 ) ,脑组织局部细胞外钙离子浓度显著降低 (P <0 .0 1) ;电针组治疗后与模型组比较 ,VEGF和Flk 1表达增强 (P <0 .0 5 ) ,而脑组织局部细胞外钙离子浓度升高 (P <0 .0 5 )。结论 :电针可以增强急性脑缺血大鼠梗死灶周围VEGF、Flk 1的表达和升高局部细胞外钙离子浓度 ,从而减轻缺血后脑损伤 ,促进脑功能的康复。