沙门菌- 斑马鱼感染模型用于Th1/Th2 免疫应答的研究

目的:通过构建斑马鱼成鱼感染模型,研究鼠伤寒沙门菌感染对机体Th1/Th2免疫应答的影响。方法:用不同剂量细菌口饲感染8月龄的斑马鱼成鱼,绘制3周生存率曲线。观察各剂量下对成鱼的感染情况,并用实时荧光定量聚合酶链式反应检测肝脏Th1、Th2型细胞相关基因和细胞因子的mRNA转录水平,计算Th2/Th1相对表达量比值。结果:用105 CFU感染2周斑马鱼全部存活,第15天开始出现死亡,且在3周后死亡率达到50%;感染后3周解剖发现,肝脏、脾脏和肠道有明显红肿和糜烂;肝脏Th1、Th2型细胞相关基因和细胞因子mRNA转录水平明显向Th2偏移。结论:用105 CFU鼠伤寒沙门菌口饲感染斑马鱼成鱼构建的模型,能反映机体感染和免疫功能变化,可用于研究体内Th1/Th2免疫应答,为进一步研究鼠伤寒沙门菌感染与免疫机制提供了很好的实验工具。     

Lipid emulsion therapy in women with recurrent pregnancy loss and repeated implantation failure: The role of abnormal natural killer cell activity

Altered immune and/or inflammatory response plays an important role in cases of recurrent pregnancy loss (RPL) and repeated implantation failure (RIF). Exacerbation of the maternal immune response through increased NK cell activity and inflammatory cytokines can cause embryo rejection leading to abortion or embryo implantation failure. Immunosuppressors or immunomodulators can help or prevent this condition. Currently, lipid emulsion therapy (LET) has emerged as a treatment for RPL and RIF in women with abnormal NK cell activity, by decreasing the exacerbated immune response of the maternal uterus and providing a more receptive environment for the embryo. However, the mechanisms by which the intralipid acts to reduce NK cell activity are still unclear. In this review, we focus on the studies that conducted LET to treat patients with RPL and RIF with abnormal NK cell activity. We find that although some authors recommend LET as an effective intervention, more studies are necessary to confirm its effectiveness in restoring NK cell activity to normal levels and to comprehend the underlying mechanisms of the lipids action in ameliorating the maternal environment and improving the pregnancy rate.     

先兆流产患者阴道微生态与Th1及Th2细胞因子的关系探讨

目的 探讨先兆流产患者阴道微生态与Th1及Th2类细胞因子的关系。 方法 回顾性分析2019年2月-2020年2月医院收治的98例先兆流产患者的资料,记为A组,另回顾性分析同期在该院体检的92例健康孕妇的资料,记为B组。对比A组和B组阴道微生物菌群组成,对比A组和B组血清Th1及Th2类细胞因子水平,采用Pearson相关性分析,分析先兆流产患者阴道微生物菌群相对丰度与血清Th1及Th2类细胞因子水平的相关性。 结果 A组阴道微生物群Chao1指数、Shannon指数均低于B组(P结论 先兆流产患者阴道微生物菌群分布与血清Th1及Th2细胞因子水平相关。     

Th1/Th2平衡调节与疾病发生的研究进展

正常情况下,辅助性T淋巴细胞亚群Th1/Th2细胞处于平衡状态,Th1/Th2平衡失调并向Th1或Th2状态转化的趋势称为Th1/Th2的漂移。习惯上把Th1及其细胞因子占优势的状态称为Th1状态,Th2及其细胞因子占优势的状态称为Th2状态。Th1/Th2平衡影响细胞因子网络的平衡,与许多疾病的发生、发展、治疗、转归有密切的关系。现就Th1/Th2平衡与人类相关疾病间的关系及相关研究作一综述。     

Apolipoprotein E genotyping in women with recurrent pregnancy loss: An in silico and experimental hybrid study

The role of apolipoprotein E gene polymorphisms in the pathogenesis of recurrent pregnancy loss remains controversial. Therefore, our objective was to investigate the association between recurrent pregnancy loss and apolipoprotein E gene polymorphisms among northwest Iranian women, and also to predict the impact of these nonsynonymous single nucleotide polymorphisms on structure and function of apolipoprotein E protein. The subjects of our current study consisted of 100 women that have had two or more consecutive idiopathic first trimester miscarriages, and one hundred healthy women from the same geographical areas were used as a control group. After DNA extraction, we used a polymerase chain reaction–restriction fragment length polymorphism to genotype of the apolipoprotein E gene. In addition, we predicted the possible effects of amino acid substitutions at codons 112 and/or 158 on the structure and function of apolipoprotein E protein using Polymorphism Phenotyping online software v2. Our results showed that the rate of apolipoprotein E ε4 carriers and the frequency of the ε4 allele in the case group were statistically and significantly higher than those in the control group (P < 0.05). Therefore, our data support the association of the Apo ε4 allele with RPL; however, in silico analysis predicted that the amino acid substitution at residue 112 (Apo ε4 allele) is a benign mutation. Accordingly, further studies are required to elucidate the mechanism(s) underlying the link between RPL pathogenesis and the Apo ε4 allele.     

Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: A meta-analysis

Background

Recurrent pregnancy loss is an important clinical problem. Recently, high-level homocysteine in blood has been considered as a possible cause. Genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) have been proved to be the common hereditary factors of high-level homocysteine. The association between MTHFR polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported but with controversial results. The purpose of present study is to collect and analyze published available data, and evaluate the association between MTHFR polymorphisms and URPL.

Methods

A meta-analysis was performed to examine the association between MTHFR polymorphisms (C677T and A1298C) and URPL. Odds ratio (OR) and its 95% confidence interval (CI) were used in each study of genotype and allele contrast.

Result(s)

MTHFR C677T: The analysis included 3559 URPL cases and 5097 healthy controls. Overall random-effects odds ratios (ORs) were 1.68 (95% CI, 1.32–2.13; P < 0.0001) for TT versus total genotypes, 1.35 (95% CI, 1.04–1.76; P = 0.0224) for TT and CT genotype combined versus total genotypes and 1.34 (95%CI, 1.13–1.58; P < 0.0001) for T versus total alleles. Although significant heterogeneity was found in C677T, it became weaker in the East Asian subgroup and the mixed subgroup when separated by ethnic subgroups. The results showed significant association between MTHFR C677T and URPL in the East Asian subgroup (ORs 2.11 for TT versus total genotype (P = 0.0004) and 1.53 for T versus total alleles (P < 0.0001)) and in the mixed subgroup (ORs 3.47 for TT versus total genotypes (P < 0.0001) and 1.80 for T versus total alleles (P < 0.027)), but not in Caucasian subgroup.

MTHFR A1298C

The study involved 1163 URPL cases and 1061 healthy controls. Overall random-effects odds ratios (ORs) were 1.37 (95% CI, 0.71–2.67; P = 0.3456) for CC versus total genotypes, 1.16 (95%CI, 0.98–1.38; P = 0.0833) for CC + AC versus total genotypes and 1.04 (95%CI, 0.84–1.29; P = 0.7112) for C versus total alleles. No significant association between MTHFR A1298C polymorphism and URPL was found.

Conclusions

These results indicate a significant association between MTHFR C677T mutation and URPL in the East Asian subgroup and mixed subgroup, but no significance in MTHFR A1298C mutation.     

T-helper (Th)1/Th2 imbalance in the peripheral blood of dogs with malignant tumor

T helper type 1 cell (Th1)/Th2 imbalance has been observed in a variety of pathological conditions, including malignant diseases. We evaluated the Th1/Th2 in peripheral blood Th cells by means of intracytoplasmic cytokine analysis in 11 dogs with advanced malignant tumor; four of them showed metastatic tumor. The percentage of Th1 was significantly lower and the percentage of Th2 was significantly higher in diseased dogs compared to healthy dogs. The percentage of Th1 in three patients with metastatic tumor was significantly lower than that in the patients with non-metastatic tumor. We conclude that the Th1/Th2 balance was polarized to Th2 in dogs with cancer.     

轮状病毒致乳鼠肠道外感染Th1/Th2细胞因子变化的研究

目的通过复制轮状病毒（RV）肠道外感染乳鼠的动物模型,检测接种后乳鼠体内Th1/Th2平衡改变,对RV肠道外感染后机体免疫状态进行初步研究。方法48只乳鼠随机均分为3组：肠道外组、肠道内组和正常对照组。肠道外组通过腹腔注射猴RVSA11株,肠道内组灌胃等量RV悬液,对照组无特殊处理。分别在接种后第4天、第8天处死乳鼠,收集标本,观察心、肝、肾、肺等脏器病理变化,用ELISA法检测血清中IL-10和IFN-γ的表达。结果光镜下肠道外组乳鼠肾、肝、肺和脾脏出现病理改变。感染后第4天,肠道内、外组乳鼠血清IFN-γ水平均高于正常组,到第8天明显下降,基本达到基线水平;IL-10在肠道外组第4天增高,到第8天小幅下降,但仍然高于正常组;而肠道内组IL-10无明显改变。结论RV肠道外感染早期呈现Th1-Th2混合反应,而后期则以IL-10的表达为主,T细胞向Th2型免疫应答方向偏离,Th1/Th2细胞因子失衡机制可能是RV肠道外感染的重要因素。     

Th1/Th2类细胞因子的变化对急性免疫性肝损伤的影响研究

目的探讨Th1/Th2类细胞因子的变化对ConA诱导的急性免疫性肝损伤的机制,以及脾脏对急性免疫性肝损伤的影响作用。方法将Balb/c小鼠随机分为两组：正常对照组,肝损伤组。正常对照组尾静脉注射等量生理盐水,肝损伤组尾静脉注射12.5mg/Kg ConA一次。各组分别于ConA注射后8h,24h,72h取材,进行下列研究：①HE染色观察各组小鼠肝脏病理学改变。②经眼球取血,收集血清测ALT和AST。③收集各组小鼠血清及新鲜肝、脾组织（各100mg）,获取肝、脾组织裂解液。用多参数细胞因子检测技术即FlowCytomix技术,通过流氏细胞仪对荧光素PE信号强度的检测,实现对各组小鼠血清、肝组织、脾组织内多种Th1/Th2类因子的定性定量分析。结果①HE染色：正常对照组肝组织结构正常。肝损伤组8h时表现为急性肝损伤表现,24h时可见大片坏死灶,72h时肝损伤缓解。②血清ALT和AST检测：正常对照组3个时间点内无明显升高,肝损伤组3个时间段内ALT和AST均高于正常对照组,有显著性差异。③Th1/Th2细胞因子检测结果：肝脏：肝损伤组8h时Th1和Th2类细胞因子均明显升高,与正常对照组比较有显著性差异,24h后开始下降,降至正常水平或正常水平以下,呈明显下降趋势。血清：肝损伤组Th1,Th2类细胞因子8h均升高,24h后逐步降低。脾脏：肝损伤组Th1,Th2类细胞因子8h时均升高,与正常对照组比较,有显著性差异,24h时明显降低。结论①ConA诱导的急性免疫性肝损伤主要是由Th1类细胞、巨噬细胞和Th2类细胞分泌的炎性因子所造成。②脾脏通过Th1/Th2类细胞因子的分泌对急性免疫性肝损伤起到免疫调控作用。     

Th1/Th2与PCT检测在感染性疾病诊断中的临床应用

病原微生物引起的感染性疾病是临床中极为常见的一类疾病,此类疾病的预后主要取决于感染的病原微生物类型及疾病的严重程度。早期诊断和积极干预可在很大程度上改善感染性疾病患者的预后。因此,快速、有效地识别感染的病原微生物并对其进行靶向治疗,避免抗生素的滥用显得尤为重要。Th1/Th2在感染性疾病中的作用越来越得到重视,而降钙素原(PCT)是临床感染性疾病诊断和鉴别诊断的早期指标,且具有高度的敏感性和特异性。Th1/Th2和PCT的联合检测对感染性疾病的诊断、病情评估和疗效监测都具有重要的意义。     

原发性肝癌患者Th1/Th2 亚群研究*

目的:探讨原发性肝癌患者血清中淋巴细胞亚群中Th1/Th2的变化,为分析肝癌的发生发展状症和临床治疗提供免疫学指标。方法:应用放射免疫分析及酶联免疫分析法(ELISA),测定46例肝癌患者,及43例正常对照组进行比较。以IL-2、INF-γ和TNF-α水平代表Th1型细胞因子,以IL-4,IL-6、IL-8、IL-10的水平代表Th2型细胞因子。结果:肝癌患者IL-2、TNF-γ、IL-6的水平明显低正常对照组,P<0.01。IL-4、IL-8、IL-10、TNF-α的水平明显高于正常对照组,P<0.01。结论:肝癌患者体内存在Th1/Th2细胞因子失衡,其中Th1亚群功能抑制,Th2亚群功能亢进,其与肿瘤在宿主体内生长密切相关。通过纠正这些免疫失调将成为肝癌治疗的重要手段。     

菌群失调小鼠感染鼠伤寒沙门菌后Th1和Th2细胞因子的动态研究

目的研究鼠伤寒沙门菌感染小鼠在菌群失调下Th细胞因子的动态变化,以探讨菌群失调对沙门菌感染的免疫机制。方法分别建立菌群失调、感染和空白对照的小鼠模型。各组动物在感染不同时点处死,观察小肠、肝脏和脾脏病理改变。采用流式细胞仪检测脾脏细胞中IFN-γ和IL-4表达,以此代表Th1和Th2细胞。结果菌群失调组病理损害最重,Th1明显增加,表达水平高,Th2变化不大,Th1/Th2比值升高。结论菌群失调后,能够加重小鼠感染鼠伤寒沙门菌引起的的Th1型反应,产生炎症性损伤。     

Bulleyaconitine A inhibits the lung inflammation and airway remodeling through restoring Th1/Th2 balance in asthmatic model mice

ABSTRACT

The current study aimed to study the effects of Bulleyaconitine A (BLA) on asthma. Asthmatic mice model was established by ovalbumin (OVA) stimulation, and the model mice were treated by BLA. After BLA treatment, the changes in lung and airway resistances, total and differential leukocytes in the bronchoalveolar lavage fluid (BALF) were detected, and the changes in lung inflammation and airway remodeling were observed. Moreover, the secretion of IgE, Th1/Th2-type and IL-17A cytokines in BALF and serum of the asthmatic mice were determined. The resuts showed that BLA attenuated OVA-induced lung and airway resistances, inhibited the inflammatory cell recruitment in BALF and the inflammation and airway remodeling of the asthmatic mice. In addition, BLA suppressed the secretion of IgE, Th2-type cytokines, and IL-17A, but enhanced secretions of Th1-type cytokines in BALF and serum. The current study discovered that BLA inhibited the lung inflammation and airway remodeling via restoring the Th1/Th2 balance in asthmatic mice.     

盐酸艾司洛尔联合右美托咪定对肺癌患者应激反应和Th1/Th2型细胞因子的影响

摘要 目的：探讨盐酸艾司洛尔联合右美托咪定对肺癌患者应激反应和辅助性T细胞1（Th1）/Th2型细胞因子的影响。方法：选取武汉科技大学附属天佑医院2020年6月~2022年3月期间收治的肺癌根治术患者112例。按照随机数字表法将患者分为对照组（n=56,常规麻醉联合盐酸右美托咪定注射液）和研究组（n=56,对照组基础上联合盐酸艾司洛尔注射液）。对比两组苏醒质量、肺功能指标、应激反应指标、Th1/Th2型细胞因子和术后肺部并发症发生率变化情况。结果：研究组的呼吸恢复时间、定向力恢复时间、拔管时间短于对照组（P<0.05）。研究组术后肺部并发症发生率低于对照组（P<0.05）。研究组术毕动态肺顺应性（Cdyn）高于对照组,平台压（Pplat）、气道峰压（Ppeak）低于对照组（P<0.05）。研究组术毕皮质醇（Cor）、去甲肾上腺素（NE）及肾上腺素（E）低于对照组（P<0.05）。研究组术毕肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）低于对照组（P<0.05）,研究组术毕白细胞介素-10（IL-10）、转化生长因子-β1（TGF-β1）高于对照组（P<0.05）。结论：盐酸艾司洛尔联合右美托咪定用于肺癌根治术中,具有较好的麻醉效果,可有效减轻术中应激反应,调节免疫功能并保护肺功能,还可降低术后肺部并发症发生率。