Rho激酶在小型猪白介素-1β介导的冠状动脉痉挛中的作用机制

目的探讨Rho激酶途径在冠状动脉痉挛发病中的作用机制。方法小型雄性家猪随机分为对照组(n=8)和模型组(n=8),冠状动脉外膜分别包裹吸附含生理盐水和白介素(IL)-1β琼脂糖微粒悬液的纸巾。2周后,采用冠状动脉造影观察管腔狭窄程度及5-羟色胺诱发冠状动脉痉挛情况。测定冠状动脉包裹血管段Rho激酶mRNA表达、肌球蛋白结合亚基磷酸化表达及光镜病理学改变。结果冠状动脉外膜包裹IL-1β血管段发生不同程度的管腔狭窄,5-羟色胺可诱发病变血管段痉挛。模型组与对照组相比,Rho激酶的mRNA表达病变血管段明显上调[(98·20±7·66)%对(63·70±4·26)%,P<0·05];肌球蛋白轻链磷酸酶的肌球蛋白结合亚基磷酸化表达升高(25485±4745对6510±779,P<0·05)。光镜可见病变血管段内膜增殖及炎症细胞聚集现象。结论Rho激酶参与IL-1β介导的冠状动脉痉挛的发生,其可能是通过增加肌球蛋白结合亚基磷酸化水平,抑制肌球蛋白轻链磷酸酶活性及加强钙增敏途径所致。     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

AIM:To study the inflammatory bowel disease-5 locus（IBD5）and interleukin-23 receptor（IL23R）gene variants in UC patients and test for gene-gene interaction.METHODS:The study population（n=625）was comprised of 320 unrelated ulcerative colitis（UC）patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus（IGR2198a₁ rs11739135,IGR2096a₁ rs12521868,IGR2230a₁ rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367）and two of the IL23R gene（rs1004819,rs2201841）were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency（P=0.032）in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers（P=0.004,OR=1.606;95%CI:1.160-2.223）and the SNP rs2201841 for homozygotes（P=0.030,OR=1.983;95%CI:1.069-3.678）.Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a₁ C or IGR2096a₁ T allele,the highest OR was calculated in the presence of SLC22A4T allele（P=0.005,OR=2.015;95%CI:1.230-3.300）.There was no association with UC for any combinations of rs1004819 and IGR2230a₁.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.     

阿托伐他汀通过抑制炎症反应减轻高胆固醇血症兔动脉粥样硬化

目的 探讨白细胞介素（interleukin,IL）-17、IL-10和基质金属蛋白酶（matrix metalloproteinase,MMP）-12在动脉粥样硬化发病机制中的作用,并进一步了解阿托伐他汀对动脉粥样硬化的干预机制.方法 18只日本大耳白兔,随机分为正常对照组、模型组和干预组,每组6只.对照组喂食基础饲料,模型组喂食高脂饲料,干预组喂食高脂饲料加阿托伐他汀5 mg/（kg·d）,饲养时间均为12周.采用酶比色法检测血清总胆固醇（total cholesterol,TC）和三酰甘油（triglyceride,TG）水平,采用选择性沉淀法测定血清低密度脂蛋白胆固醇（low-density lipoprotein cholesterol,LDL-C）和高密度脂蛋白胆固醇（high-density lipoprotein cholesterol,HDL-C）水平,采用双抗体夹心酶联免疫吸附法测定血清IL-17、IL-10和MMP-12水平.HE染色观察动脉粥样硬化斑块病理形态学变化,应用图像分析软件计算内膜厚度、内膜/中膜比、斑块面积及斑块比例.结果 干预组血清TC、TG、LDL-C水平以及IL-17和MMP-12表达水平均显著性低于模型组（P均＜0.05）,但仍略高于对照组（P＜0.05）,HDL-C水平无显著性差异.干预组血清IL-10水平均显著性高于对照组和模型组（P均＜0.05）.干预组内膜厚度、内膜/中膜比、斑块面积和斑块比例均较模型组显著性降低（P均＜0.05）.相关分析显示,斑块比例与IL-17（r =0.847,P=0.001）和MMP-12（r=0.839,P=0.001）均呈显著正相关,与IL-10呈显著负相关（r=-0.794,P=0.002）;IL-17与MMP-12呈显著正相关（r=0.709,P =0.001）,与IL-10呈显著负相关（r=-0.738,P＜0.001）,MMP-12与IL-10水平呈显著负相关（r=-0.563,P=0.015）.结论 IL-17和MMP-12水平增高以及IL-10水平降低说明炎性因子在动脉粥样硬化的发病机制中起着重要的病理学作用.阿托伐他汀除降脂作用外,还可能通过减少IL-17和MMP-12以及增加IL-10的表达,降低动脉慢性炎症反应程度而发挥抗动脉粥样硬化作用.     

诱导痰中白介素8和可溶性细胞间黏附分子1动态变化与慢性阻塞性肺疾病气道炎症的相关性

目的 观察慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)不同时期诱导痰中白介素8(IL-8)、可溶性细胞间黏附分子1(sICAM-1)水平的变化情况,探讨两者对COPD病情评估所起的作用.方法 20名健康人为对照组,40例COPD患者,采用ELISA法检测对照组...     

调节性T细胞源性IL-10与TGF-β1对破骨细胞分化及骨吸收的抑制作用

示出对破骨细胞分化与骨吸收功能明显的协同抑制作用.结论 调节性T细胞源性细胞因子IL-10与TGF-β1对破骨细胞分化与骨吸收功能具有抑制作用.     

白细胞介素-23对炎症性肠病患者外周血自然杀伤细胞的免疫调节作用

目的 研究白细胞介素(IL)-23对炎症性肠病(IBD)患者外周血中自然杀伤(NK)细胞促炎细胞因子分泌和细胞毒作用的影响,探讨其在IBD发病中的意义.方法 利用免疫磁珠分离12名健康人、16例克罗恩病(CD)患者和25例溃疡性结肠炎(UC)患者外周血NK细胞.体外培养NK细胞,并予空白刺激、IL-23刺激、IgG刺激或IL-23+IgG联合刺激.酶联免疫吸附试验法检测细胞培养上清中肿瘤坏死因子(TNF)-αa和干扰素(IFN)-γ分泌水平.流式细胞仪检测经不同刺激培养的NK细胞对K562细胞的细胞毒作用.结果 正常对照组的NK细胞经人IgG和IL-23单独刺激后TNF-α、IFN-γ的分泌水平未明显增高(P值均＞0.05),二者联合刺激则能显著促进TNF-α、IFN-γ分泌(P值均＜0.05).单独应用IgG刺激CD和UC患者NK细胞分泌TNF-α、IFN-γ的效果不明显(P值均＞0.05).单独应用IL-23则具刺激作用(P值均＜0.05),二者联合应用的刺激作用更明显(P值均＜0.01).IL-23单独刺激和联合刺激均不能增强正常对照组NK细胞的细胞毒作用(P值均＞0.05).但单独应用IL-23可增强UC和CD患者NK细胞的细胞毒作用(分别为51.5%±7.1%和50.2%±8.7%,P值均＜0.05),且联合刺激可进一步增强该作用(分别为65.3%±6.6%和62.4%±5.5%,P值均＜0.01).结论 IL-23能刺激IBD患者NK细胞分泌TNF-α和IFN-γ,并能增强NK细胞的细胞毒作用,可能直接参与了IBD的发病过程.     

Th17细胞与Smads蛋白家族间的相互作用研究进展

Th17细胞作为一种新发现的Th细胞亚型主要分泌IL-17、IL-17F和IL-21,被认为在清除特定的病原体和诱导自身免疫组织炎症反应中发挥重要作用。Smads蛋白是重要的TGF-β受体胞内激酶的底物,磷酸化后可穿越胞膜,因此既是胞内信号分子,又起到转录子的作用。本文对当前国内外有关Th17细胞分化及功能的研究进展以及Th17细胞与Smad蛋白之间的相互作用做简要综述。     

不同剂量氟伐他汀对急性冠状动脉综合征患者血管内皮功能及炎症因子的影响

目的探讨较大剂量与常规剂量氟伐他汀相比,对急性冠脉综合征(ACS)患者是否有进一步的改善血管内皮功能和抗炎的作用。方法收集本院ACS患者120例,常规治疗基础上随机给予氟伐他汀40mg(40mg组)或氟伐他汀80 mg(80 mg组),每晚睡前服用。治疗4周,测定治疗前后患者血清NO、Hs-CRP、IL-6、HSP60的水平,随访临床事件发生情况。结果两组患者治疗4周后血清NO水平均有所升高[40 mg组:(56.68±12.01)μmol/L比(74.49±12.38)μmol/L,P<0.05;80mg组:(51.29±14.67)μmol/L比(82.57±12.17)μmol/L,P<0.01],且80 mg组患者血清NO水平升高更明显(P<0.05)。两组患者血清Hs-CRP、IL-6、HSP60水平均有所下降[40mg组分别为:(14.79±12.68)mg/L比(6.17±4.68)mg/L,(47.96±37.54)ng/L比(36.21±20.06)ng/L,(6.36±1.24)μg/L比(3.14±1.09)μg/L,P<0.05;80 mg组分别为:(14.48±12.32)mg/L比(4.31±3.56)mg/L,(50.35±40.17)ng/L比(31.24±15.49)ng/L,(6.25±1.16)μg/L比(1.25±0.98)μg/L,P<0.01],且80mg组下降更明显(均为P<0.05)。临床事件的随访观察显示,40 mg组共有10例(16.67%)患者发生心血管事件,80 mg组仅有4例(6.67%)发生心血管事件,发生率两组间差异有统计学意义(P<0.05)。结论氟伐他汀可升高ACS患者血清NO水平,降低Hs-CRP、IL-6及HSP60水平,其改善血管内皮功能和抗炎作用在短期内呈剂量依赖性。较大剂量氟伐他汀早期强化治疗可以明显减少ACS患者近期心血管事件的发生率,且安全性良好。     

中国沿海地区汉族男性人群白细胞介素-1β-31C/T基因多态性与痛风的易感性研究

目的 探讨山东省沿海地区中国汉族男性群体的白细胞介素(IL)-1β启动子区rs1143627(-31C/T)基因多态性的分布状况及其与痛风易感性之间的关系.方法 选取208例痛风患者和210名健康对照者,应用聚合酶链反应限制性片段长度多态性(RFLP)技术,检测中国汉族男性群体的IL-1β启动子区rs1143627(-31C/T)位点基因多态性与痛风发病的遗传易感性的关系.采用Hardy-Weinberg检验确认标本的群体代表性,数据分析采用χ2检验和t检验.结果 痛风组中IL-1β启动子区-31C/T位点CC,CT和TT基因型分别为32.7%,43.3%和24.0%,健康对照组分别为31.9%,46.2%和21.9%,2组比较差异无统计学意义(χ2=0.427,P>0.05);2组的等位基因频率C和T间差异也无统计学意义(分别为54.3%,55.0%;45.7%,45.0%;χ2=0.038,P>0.05).经χ2检验,IL-1β基因-31C/T位点基因多态性与痛风病的危险因素无显著性关联.结论 尚不能认为中国沿海地区汉族男性人群中IL-1β启动子区rs1143627(-31C/T)基因多态性与痛风有关联性.

Abstract：

Objective To explore gene polymorphism of the C/T genotype of rs1143627 in the promoter of IL-1β gene in male population living in the coastal area of Shandong, and thus to investigate the relationship between the gene polymorphism of IL-1β and gout. Methods A total of 208 gout patients and 210 healthy controls were enrolled. The possible association between the polymorphism of IL-1 β -3 1C/T and gout in Chinese were investigated and genotype frequencies and allelic frequencies was calculated by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Hardy-Weinberg was used to verify the representativeness of the sample. Comparisons between the groups were performed with χ2 test and t-test. Results The frequencies of CC, CT, and TT genotypes were 32.7%, 43.3% and 24.0%,respectively among gout patients, while they were 31.9%,46.2% and 21.9%, respectively among the controls.There was no statistically difference in IL-1β -31C/T genotype frequencies between gout patients and controls (χ2=0.427, P>0.05). The allele frequencies of C and T in gout cases were different from those in the controls (54.3%, 55.0%; 45.7%, 45.0%; χ2=0.038, P>0.05). Moreover, no association between IL- I β-31 C/T genotypes and risk factors for gout were observed in gout cases by χ2 test. Conclusion Results of the present study suggest that the C/T genotype of rs1143627 in the promoter of IL-1β gene is not associated with gout in male population living in the coastal area of Shandong.