脑血管病急性期MMP-9、IL-6和IL-10水平变化的研究

目的：探讨基质金属蛋白酶‐9（MMP‐9）、白细胞介素‐6（IL‐6）和白细胞介素‐10（IL‐10）与脑动脉粥样硬化斑块不稳定性以及脑梗死的关系。方法选择急性脑血管病患者56例,其中反复短暂性脑缺血发作（TIA）16例,急性脑梗死40例。对照组为21例健康体检者。所有缺血性脑血管病患者均经头CT血管造影（CTA）检查或颈部血管超声证实存在不稳定斑块,且发病机制考虑与不稳定斑块破裂有关。采用ELISA方法检测各组血清MMP‐9、IL‐6和IL‐10水平并进行比较。结果急性脑梗死组患者血清中MMP‐9、IL‐10水平分别为（137.10±69.38）ng/mL和（39.16±32.82）pg/mL,TIA组患者血清中MMP‐9、IL‐10水平分别为（119.79±65.54）ng/mL和（33.00±21.36）pg/mL,均明显高于对照组〔分别为（65.42±36.81）ng/mL和（19.83±12.16）pg/mL〕;脑梗死组患者血清MMP‐9及IL‐10水平均高于TIA组（均P＜0.05）。各组间IL‐6水平差异无统计学意义（均P＞0.05）。结论MMP‐9和IL‐10水平升高可能与动脉粥样硬化不稳定斑块破裂以及脑梗死灶形成有关。     

多种脂肪细胞因子与脑梗死患者颈动脉粥样硬化斑块稳定性的关系

目的探讨多种脂肪细胞因子与急性脑梗死(ACI)患者颈动脉粥样硬化斑块稳定性的关系。方法根据颈动脉彩色多普勒超声仪检查结果,将113例ACI患者分为无斑块组、稳定斑块组和不稳定斑块组;采取酶联免疫法检测ACI患者发病<48h和14d时以及31名健康对照者的血清脂联素、抵抗素、内脏脂肪素、白介素-6(LI-6)和白介素-8(LI-8)的水平。结果 (1)ACI患者发病<48h和14d时血清内脏脂肪素、抵抗素、LI-6、LI-8水平明显高于对照组,脂联素水平明显低于对照组。与发病<48h相比,ACI患者发病14d时血清内脏脂肪素、抵抗素、LI-6、LI-8水平明显升高,脂联素水平明显降低。(2)不稳定斑块组血清内脏脂肪素、抵抗素、LI-6、LI-8水平高于稳定斑块组和无斑块组,脂联素水平明显低于稳定斑块组和无斑块组。(3)血清内脏脂肪素、抵抗素、LI-6、LI-8水平与颈动脉斑块不稳定性呈正相关,而血清脂联素水平与颈动脉斑块不稳定性呈负相关。结论血清脂肪细胞因子内脏脂肪素、抵抗素、LI-6、LI-8水平升高和脂联素水平降低与脑梗死患者颈动脉粥样硬化斑块的不稳定显著相关,有望成为评价斑块稳定性及预测脑梗死发生的理想生化指标。     

血清MMP-9与脑梗死患者及其颈动脉粥样硬化斑块稳定性的关系研究

目的检测具有不同性质颈动脉粥样硬化斑块的脑梗死患者的血清基质金属蛋白酶-9（MMP-9）水平,探讨颈动脉粥样硬化斑块稳定性及相关炎性标志物MMP-9水平与脑梗死的关系。方法采用彩色多普勒超声检查48例颈内动脉系统的急性脑梗死患者（CI组）颈动脉粥样硬化斑块,同时检测患者血清MMP-9水平,并与20例慢性脑供血不足患者（CCCI组）及20例体检健康者（对照组）比较;根据斑块性质将CI组分为不稳定斑块组、稳定斑块组及无斑块组3个亚组,并进行组内比较。结果脑梗死组斑块检出率、不稳定斑块率及血清MMP9水平均明显高于慢性脑供血不足组及对照组（P〈0．05）;脑梗死不稳定斑块组MMP-9水平显著高于脑梗死稳定斑块组,脑梗死稳定斑块组高于脑梗死无斑块组（P〈0．01）。结论颈动脉粥样硬化斑块及其稳定性与脑梗死发生有密切关系,具有不同性质颈动脉斑块的脑梗死患者的血清MMP-9水平存在差异,MMP-9可能是不稳定性粥样硬化斑块及脑梗死的一个潜在的血清标志物。     

Hs-CRP、Hcy及UA与颈动脉粥样硬化的相关性研究

目的探讨血清中超敏C反应蛋白(hs-CRP)、同型半胱氨酸(Hcy)及尿酸(UA)水平与颈动脉粥样硬化的关系。方法采用彩色多普勒超声对脑梗死患者双侧颈动脉进行筛查,根据颈动脉粥样硬化程度将患者分为轻度、中度及重度狭窄组;再根据斑块的不同性质将上述脑梗死患者分为稳定性斑块及不稳定性斑块两组;分别测定86例病例组与25例正常对照组血清hs-CRP、Hcy及UA水平。结果颈动脉斑块组血清hs-CRP、Hcy及UA水平均高于正常对照组。不稳定性斑块组血清hs-CRP与UA水平均高于稳定性斑块组。结论血清hs-CRP、Hcy、UA水平升高与颈动脉粥样硬化形成密切相关;血清中hs-CRP和UA水平异常升高与不稳定斑块形成密切相关。     

TIA患者高敏C-反应蛋白水平与颈动脉粥样硬化的关系

目的探讨短暂性脑缺血发作（TIA）患者血清高敏C-反应蛋白水平与颈动脉粥样硬化斑块的关系。方法选取62例短暂性脑缺血发作患者为TIA组,同期选择健康体检者30例为对照组,应用颈动脉彩色多普勒超声检查短暂性脑缺血发作患者颈动脉粥样硬化情况,根据颈动脉超声检查,将TIA组分为不稳定斑块组、稳定斑块组,测定血清高敏C-反应蛋白水平含量并进行比较。结果 TIA组血清高敏C-反应蛋白水平显著高于对照组,P〈0.01;TIA组中不稳定粥样斑块组血清高敏C-反应蛋白水平显著高于稳定粥样斑块组,P〈0.01。结论血清高敏C-反应蛋白水平升高对短暂性脑缺血发作患者颈动脉粥样硬化不稳定斑块有显著临床意义,早期测定高敏C-反应蛋白水平有助于评估短暂性脑缺血发作患者的脑卒中风险。     

急性缺血性脑血管病患者血清ox-LDL及PAPP-A水平与颈动脉粥样硬化的相关性研究

目的探讨急性缺血性脑血管病患者颈动脉粥样硬化与血清氧化型低密度脂蛋白(ox-LDL)、妊娠相关血浆蛋白A(PAPP-A)水平的关系。方法随机选取急性脑梗死患者90例和短暂性脑缺血发作(TIA)患者60例作为研究对象,随机选取健康体检者30例作为对照组。入选者均检测血清ox-LDL、PAPP-A水平。对急性脑梗死和TIA患者进行颈动脉超声检查,发现颈动脉内-中膜厚度(IMT)正常者22例,IMT增厚者47例,颈动脉斑块形成者81例,其中稳定斑块者49例,不稳定斑块者32例。比较各组血清ox-LDL及PAPP-A水平。结果急性脑梗死组血清PAPP-A及ox-LDL水平显著高于TIA组(P<0.01),后者显著高于正常对照组(P<0.01);在缺血性脑血管病患者中,颈动脉粥样硬化斑块形成者血清PAPP-A及ox-LDL水平较颈动脉IMT增厚组明显升高(P<0.01),后者高于IMT正常组(P<0.01);在颈动脉斑块形成者中,其血清PAPP-A及ox-LDL水平在不稳定斑块组高于稳定斑块组(P<0.01)。Spearman分析显示,血清PAPP-A与ox-LDL水平之间存在明显相关性(r=0.839,P<0.05);logistic回归分析显示,血清PAPP-A与ox-LDL水平是发生颈动脉粥样硬化的危险因素(OR=2.549,95%CI1.12~3.79;OR=1.317,95%CI1.15~2.11)。结论急性缺血性脑血管病患者颈动脉粥样硬化的发生和进展与ox-LDL、PAPP-A水平相关,血清ox-LDL及PAPP-A水平可在一定程度上反映急性缺血性脑血管病患者颈动脉粥样硬化的程度。两者在颈动脉甚至颅内动脉粥样硬化的形成过程中产生协同作用。     

颈动脉粥样斑块与缺血性脑血管病的相关性

目的探讨中国北方中老年人群(>45岁)颈动脉硬化斑块的性质与缺血性脑血管病的关系。方法采用回顾性研究,随机抽取北方某社区中老年常规体检者中,经头部CT或MRI证实113例脑梗死患者及反复发作性TIA患者8例(脑血管病组)和94例非脑血管病者(对照组),采用颈部血管彩超比较两组颈部动脉硬化斑块性质、分布、数量、形态和回声特征差异,以探讨缺血性脑血管病与颈部血管动脉硬化斑块之间的相关性。结果脑血管病组不稳定性斑块阳性率82.6%,显著高于对照组不稳定性斑块阳性率56.4%(P<0.01)。结论颈部动脉不稳定性斑块与缺血性脑血管病的发生率存在相关。     

急性脑梗死患者颈动脉粥样硬化斑块与血液炎症因子水平的关系

目的探讨急性脑梗死患者颈动脉粥样硬化斑块与血液炎症因子水平的关系。方法 164例急性脑梗死患者经颈动脉超声检查分为无斑块组(42例)、稳定斑块组(58例)及不稳定斑块组(64例);其中Ⅰ、Ⅱ、Ⅲ级斑块各为37、45、40例。检测各组患者血清超敏C反应蛋白(hs-CRP)及血浆肿瘤坏死因子-α(TNF-α)、白介素6(IL-6)水平,并进行比较。结果稳定斑块组及不稳定斑块组血清hs-CRP及血浆TNF-α、IL-6水平明显高于无斑块组(均P<0.05);不稳定斑块组明显高于稳定斑块组(均P<0.05)。且随着斑块严重程度的增加,其血清hs-CRP及血浆TNF-α、IL-6水平也明显增高(均P<0.05)。结论血清hs-CRP及血浆TNF-α、IL-6水平可以反映急性脑梗死患者颈动脉粥样硬化的严重程度。     

颈动脉粥样硬化斑块形成与脑梗死的相关研究

目的探讨颈动脉粥样硬化斑块因素与脑梗死的关系。方法将我科2009-05-2011—07收治的颈动脉粥样硬化斑块形成患者175例分为脑梗死组（研究组）112例,无脑梗死组（对照组）63例,对照分析2组的颈动脉粥样硬化斑块特点及临床表现异同点。结果脑梗死组颈动脉粥样硬化斑块发生率高于对照组,脑梗死组颈动脉内中膜厚度（IMT）大于对照组,脑梗死组斑块中软斑块比例高于对照组,脑梗死组与对照组患者均有短暂性脑缺血发作（TIA）症状,脑梗死组TIA发作次数及频率均高于对照组。结论颈动脉粥样硬化斑块是导致脑梗死的重要因素之一,脑梗死患者的颈动脉粥样硬化斑块数量相对较多,且以不稳定软斑块为主,应早期对其进行干预。     

ABCD~2评分联合颈动脉超声对TIA后早期发生脑梗死的预测价值

目的探讨ABCD2评分联合颈部血管超声对短暂性脑缺血发作后7d内发生脑梗死的预测价值。方法收集颈内动脉系统TIA患者80例,并根据ABCD2评分及颈部血管超声结果进行分组,比较各组患者TIA后7d内脑梗死发生率。结果80例TIA患者7d内进展为脑梗死共18例(22.5%),低、中、高危组患者7d内进展为脑梗死的比例分别为6.9%、27.3%、38.9%,各组比较差异有统计学意义(P0.05)。颈动脉超声斑块组和无斑块组脑梗死发生率分别为47.1%、4.3%(P0.05)。ABCD2评分≥4分的患者中,颈动脉超声斑块组脑梗死发生率为54.2%,高于无斑块组(11.1%)(P0.05)。结论 ABCD2评分联合颈动脉超声对评估短暂性脑缺血发作患者早期发生脑梗死的风险具有重要意义。     

丙种球蛋白对格林-巴利综合征患者白介素12与白介素18表达的影响及其相关性研究

目的探讨丙种球蛋白治疗对格林-巴利综合征(GBS)对患者体内白介素12(IL12)和白介素18(IL18)的表达的影响。方法用ELISA方法对静脉注射丙种球蛋白(IVIG)治疗GBS前后的血清、脑脊液IL12和IL18表达,同时用RT-RCR法检测血淋巴细胞白介素12受体(IL12R)mRNA与IL18RmRNA的表达。结果17例GBS治疗前血清IL12含量为45.6±12.2pg/ml,治疗后为17.1±4.74pg/ml(P<0.01);IL18治疗前为157.5±39.3pg/ml,治疗后为126.2±22.6pg/ml。5例GBS治疗前脑脊液IL12为25.2±5.8pg/ml,治疗后为16.7±3.6pg/ml。IL-18治疗前为121.8±27.9pg/ml,治疗后为53.6±15.6pg/ml。17例GBS治疗前血淋巴细胞表面受体IL-12RmRNA的表达强度为0.2948±0.098,治疗后为0.1507±0.087,与治疗前比显著降低(P<0.05)。治疗前血淋巴细胞IL18RmRNA表达强度为0.5352±0.1134,治疗后为0.2843±0.1127,与治疗前比显著降低(P<0.05)。IL12与IL18蛋白在血清中的表达呈显著正相关;IL12与IL18淋巴细胞表面受体mRNA的表达呈显著正相关。结论丙种球蛋白治疗能够下调GBS患者IL12与IL18的表达。     

Meta-analysis of the IL23R and IL12B polymorphisms in multiple sclerosis

Purpose: Polymorphisms in the genes encoding interleukin-23 receptor (IL23R) and the p40 subunit of IL-12/23 (IL12B) have been implicated in multiple sclerosis (MS) risk. However, results of different studies are inconsistent. Our aim was to perform a meta-analysis on this topic. Methods: We assessed two variants (rs10889677 and rs7517847) of IL23R and the A1188C polymorphism (rs3212227) of IL12B. Electronic databases (PubMed, Web of Science and Scopus) were searched for eligible studies published until September 2014. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of association in dominant, recessive, homozygote and allelic comparison models. Results: Seven case–control studies with 2250 MS patients and 2320 controls were included in this meta-analysis. The pooled results showed no association of rs10889677 and rs7517847 with MS risk in any of the genetic models. Although the pooled analysis showed an association between rs3212227 and MS in all study subjects in dominant (OR = 0.81, 95% CI: 0.66–0.99, P_h = 0.480, P_z = 0.044) and allelic comparison (OR = 0.84, 95% CI: 0.72–0.98, P_h = 0.967, P_z = 0.030) models, subgroup analysis based on ethnicity did not suggest an association between rs3212227 and MS risk in Caucasians in any of the genetic models, and there was no association between rs3212227 and MS risk in an Asian group. Conclusions: The IL23R polymorphisms rs10889677, rs7517847, and the IL12B polymorphism rs3212227 are not associated with MS risk.     

Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: suggestive association with rs16944 at IL1beta

Genetic association studies of several candidate cytokine genes have been motivated by evidence of immune dysfunction among patients with schizophrenia. Intriguing but inconsistent associations have been reported with polymorphisms of three positional candidate genes, namely IL1beta, IL1RN, and IL10. We used comprehensive sequencing data from the Seattle SNPs database to select tag SNPs that represent all common polymorphisms in the Caucasian population at these loci. Associations with 28 tag SNPs were evaluated in 478 cases and 501 unscreened control individuals, while accounting for population sub-structure using the genomic control method. The samples were also stratified by gender, diagnostic category, and exposure to infectious agents. Significant association was not detected after correcting for multiple comparisons. However, meta-analysis of our data combined with previously published association studies of rs16944 (IL1beta -511) suggests that the C allele confers modest risk for schizophrenia among individuals reporting Caucasian ancestry, but not Asians (Caucasians, n=819 cases, 1292 controls; p=0.0013, OR=1.24, 95% CI 1.09, 1.41).     

Genetic variants in IL2RA and IL7R affect multiple sclerosis disease risk and progression

Multiple sclerosis (MS) is a common demyelinating neurodegenerative disease with a strong genetic component. Previous studies have associated genetic variants in IL2RA and IL7R in the pathophysiology of the disease. In this study, we describe the association between IL2RA (rs2104286) and IL7R (rs6897932) in the Canadian population. Genotyping 1,978 MS patients and 830 controls failed to identify any significant association between these variants and disease risk. However, stratified analysis for family history of disease and disease course identified a trend towards association for IL2RA in patients without a family history (p?=?0.05; odds ratio?=?0.77) and a significant association between IL7R and patients who developed progressive MS (PrMS) (p?=?0.002; odds ratio?=?0.73). Although not statistically significant, the effect of IL2RA (rs2104286) in patients without a family history of MS indicates that the genetic components for familial and sporadic disease are perhaps distinct. This data suggests that the onset of sporadic disease is likely determined by a large number of variants of small effect, whereas MS in patients with a family history of disease is caused by a few deleterious variants. In addition, the significant association between PrMS and rs6897932 indicates that IL7R may not be disease-causing but a determinant of disease course. Further characterization of the effect of IL2RA and IL7R genetic variants in defined MS subtypes is warranted to evaluate the effect of these genes on specific clinical outcomes and to further elucidate the mechanisms of disease onset and progression.     

Effects of IL6 and IL1beta on aFGF expression and excitotoxicity in NT2N cells

The interleukin-1beta (IL1beta) and interleukin-6 (IL6) have pro-inflammatory and neuroprotective functions and are elevated in many diseases of the brain. Here, mechanisms and effects of IL1beta and IL6 on neuronal survival after excitatory stimulation were investigated in vitro. IL6 upregulated the expression of the neuroprotective acidic fibroblast growth factor (aFGF) and reduced the glutamate-induced cytotoxicity. IL1beta treatment amplified the excitotoxic effects after 24 h, but longer treatment with IL1beta stimulated the neuronal release of IL6 resulting in increased levels of aFGF and a decreased excitotoxicity. These data suggest that (1) IL6 exerts protective functions by upregulating the expression of aFGF and (2) the IL6/IL1beta balance in the brain may regulate neuronal survival during neuropathological processes.     

Association between idiopathic achalasia and IL23R gene

Background Idiopathic achalasia is a primary esophageal motor disorder of unknown etiology. Different evidences have been reported in support of achalasia as the result of an autoimmune and inflammatory process leading to neuronal cell loss. According to this, idiopathic achalasia has been significantly associated with specific alleles of the human leukocyte antigen system class II, although few reports studying association with other loci can be found in the literature. Recent studies have shown association of a non‐synonymous polymorphism within the IL23R gene with different chronic inflammatory disorders, including Barrett’s esophagus. The purpose of this study was to assess whether the IL23R coding variant Arg381Gln polymorphism is involved in susceptibility to idiopathic achalasia. Methods We performed a case‐control study including 262 patients with idiopathic achalasia and 802 healthy subjects, all of them white Spaniards. Achalasia patients were diagnosed on the basis of clinical, radiographic, endoscopic, and manometric criteria. All samples were genotyped for the IL23R Arg381Gln polymorphism using TaqMan technology. Key Results The minor allele of the Arg381Gln polymorphism was significantly increased in patients compared with healthy controls (OR = 1.46, 95% CI = 1.01–2.11, P = 0.036). This association seems to be specific to male patients with disease onset after 40 years (OR = 2.33, 95% CI = 1.29–4.16, P = 0.002). Conclusions & Inferences Our results suggest a role of IL23R in idiopathic achalasia predisposition and extend the evidence of the general influence of this gene in autoimmune and inflammatory diseases.     

Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington's syndrome

Ciliary neurotrophic factor prevents behavioural deficits and striatal degeneration in rat and primate models of Huntington's disease. Interleukin-6, another member of the cytokine family, and the chimeric molecule (IL6/IL6R) in which interleukin-6 and its soluble receptor are fused, have been shown to exert trophic action on various neuronal populations in the central nervous system. Therefore, we investigated the neuroprotective effect of these two molecules in the quinolinic acid model of Huntington's disease. LacZ-, interleukin-6- and IL6/IL6R-expressing lentiviral vectors were stereotaxically injected into the striatum of Wistar rats. Three weeks later the animals were lesioned through the intrastriatal injection of 180 nmol of quinolinic acid. The extent of the striatal damage was significantly diminished in the rats that had been treated with interleukin-6 or IL6/IL6R. The neuroprotective effect was, however, more pronounced with the IL6/IL6R chimera than with interleukin-6 as indicated by the volume of the lesions (38.6 +/- 10% in the IL6/IL6R group, 63.3 +/- 3.6% in the IL-6 group and 84.3 +/-2.9% in the control group). Quantitative analysis of striatal interneurons further demonstrated that the IL6/IL6R chimera is more neuroprotective than IL-6 on ChAT- and NADPH-d-immunoreactive neurons. These results suggest that the IL6/IL6R chimera is a potential treatment for Huntington's disease.