IL-17和YKL-40在慢性鼻—鼻窦炎患者血浆中表达及其临床意义

发布时间：2018-07-01 09:06

本文选题：IL-17 + YKL-40　；参考：《山东大学》2011年硕士论文

【摘要】：[研究背景和目的] 慢性鼻-鼻窦炎(Chronic rhinosinusitis, CRS)是临床上的常见病和多发病,至今病因不清。近年来的研究倾向于多因素作用的病因学说,而细胞炎性因子在此过程中起重要作用。白介素17是一种促炎症性细胞因子,主要是由活化的记忆CD4+T淋巴细胞所分泌,IL—17与其受体结合后可以诱导表达多种细胞因子以及粘附分子,这些细胞因子在造血过程以及免疫炎症反应等的不同阶段具有不同的作用,例如能刺激产生IL-6和PGE-2,有助于增强局部炎症的反应；能促进机体局部产生趋化因子MCP-1、Gro-a、IL-8等,有助于单核细胞和中性粒细胞的迅速聚集。YKL-40(人类软骨糖蛋白39)是哺乳类动物甲壳酶蛋白家族的一员,但没有壳质酶活性。人体内的多种细胞,如巨噬细胞、中性粒细胞、滑膜细胞及软骨细胞等均能分泌YKL-40。已有研究表明,YKL-40可以在细胞外基质降解、炎症反应、组织重建及刺激内皮细胞迁移中起作用,同时也可参与恶性肿瘤的转移过程。YKL-40的分泌和表达与组织或细胞的病理状态有很大的关系,表明其在炎症反应和结缔组织的修复过程中发挥重要作用。本实验旨在研究IL-17和YKL-40在慢性鼻-鼻窦炎患者血浆中的表达情况,探讨其参与慢性鼻-鼻窦炎发生可能的机制。 [研究方法] 手术前空腹采血,收集伴有鼻息肉慢性鼻-鼻窦炎(CRSwNP)患者38例、不伴有鼻息肉慢性鼻-鼻窦炎(CRSsNP)患者32例的血液(柠檬酸钠抗凝),对照组28例均来自于门诊体检健康者。血样经本人知情同意后采集,2000rpm离心15 min,分离血浆,于-80℃冰箱保存,采用ELISA法检测血浆中IL-17和YKL-40的含量情况。 [结果] 1.正常对照组血浆IL-17浓度为1.6100(1.2575-1.9830)pg/ml:慢性鼻-鼻窦炎患者血浆IL-17浓度8.2483(4.8868-10.1075)pg/ml；伴有鼻息肉慢性鼻-鼻窦炎(CRSwNP)患者血浆浓度IL-17 8.2430(6.2778-10.3610)pg/ml；不伴有鼻息肉慢性鼻-鼻窦炎(CRSsNP)患者血浆IL-17浓度8.2550(4.8783-10.1650)pg/ml.IL-17在正常人与慢性鼻-鼻窦炎患者血浆中表达差别有显著性(P0.05),在CRSwNP. CRSsNP组表达均明显高于正常人,推测其在慢性鼻-鼻窦炎的发生发展中起重要作用；但在CRSwNP组与CRSsNP组之间差异无显著性,支持我们将慢性鼻-鼻窦炎划分为CRSwNP和CRSsNP. 2.正常对照组血浆YKL-40浓度为18.2145(12.5878-20.8250)ng/ml；慢性鼻-鼻窦炎患者血浆YKL-40浓度48.0236(35.1520-59.9180)ng/ml；伴有鼻息肉慢性鼻-鼻窦炎(CRSwNP)患者血浆YKL-40浓度50.9490(35.1373-63.4303)ng/ml；不伴有鼻息肉慢性鼻-鼻窦炎(CRSsNP)患者血浆YKL-40浓度46.0765(37.8620～55.3008)ng/ml.YKL-40在正常人与慢性鼻-鼻窦炎患者血浆中表达差别有显著性(P0.05),在CRSwNP.CRSsNP组表达均明显高于正常人,推测其在慢性鼻-鼻窦炎的发生发展中起重要作用；但在CRSwNP组与CRSsNP组之间差异无显著性,也支持我们将慢性鼻-鼻窦炎划分为CRSwNP和CRSsNP. 3.病情严重程度的评估 3.1 VAS评分CRSwNP组VAS评分为7.21±1.65,CRSsNP组VAS评分为6.53±1.91:CRSwNP组和CRSsNP组在症状严重程度评分方面差异无统计学意义。 3.2 CT检查评分CRSwNP组鼻窦CT评分为16.01±5.98,CRSsNP组鼻窦CT评分为7.98±4.12: CRSwNP组CT评分显著高于CRSsNP组。 3.3鼻内镜检查评分CRSwNP组评分为11.75±5.68,CRSsN组评分为6.27±3.21；CRSwNP组鼻内镜检查评分显著高于CRSsNP组。 3.4病情严重程度与血浆IL-17水平之间的相关性分析统计结果显示,鼻窦CT、鼻内镜检查评分与患者血浆IL-17水平正相关,相关系数分别为(r值分别为0.710.64 P0.05).VAS评分与患者血浆IL-17水平无相关性。 [结论] 1.IL-17在正常人与慢性鼻-鼻窦炎患者血浆中表达差别有显著性(P0.05),在CRSwNP、CRSsNP组表达均明显高于正常人,推测其在慢性鼻-鼻窦炎的发生发展中起重要作用；但在CRSwNP组与CRSsNP组之间差异无显著性,支持我们将慢性鼻-鼻窦炎划分为CRSwNP和CRSsNP。 2.YKL-40在正常人与慢性鼻-鼻窦炎患者血浆中表达差别有显著性(P0.05),在CRSwNP、CRSsNP组表达均明显高于正常人,推测其在慢性鼻-鼻窦炎的发生发展中起重要作用；但在CRSwNP组与CRSsNP组之间差异无显著性,也支持我们将慢性鼻-鼻窦炎划分为CRSwNP和CRSsNP。 3.IL-17及YKL-40在慢性鼻-鼻窦炎的发生发展机制中起重要作用,两者可能存在某种协同作用,但其协同作用机制及两者之间关系有待进一步深入研究。 4.病情严重程度的评估方面,CRSwNP组和CRSsNP组在症状严重程度评分方面差异无统计学意义,而CT检查评分及鼻内镜检查评分CRSwNP组评分均高于CRSsNP组,表明CRSwNP有更为严重广泛的粘膜病变。 [研究意义] 对于慢性鼻-鼻窦炎患者,IL-17及YKL-40在其发生发展中具有重要的作用,因此可以考虑降低其含量或者阻断其作用的方式来进行治疗,例如开放窦口充分引流、手术摘除息肉、控制感染进而降低感染等导致的IL-17及YKL-40高表达的因素,或者使用IL-17R、YKL-40R阻断剂以阻断其作用.
[Abstract]:[research background and purpose]
Chronic rhinosinusitis (Chronic rhinosinusitis, CRS) is a common and frequently occurring disease in the clinic, and so far the etiology is not clear. In recent years, the study of the etiology of multiple factors has tended to play an important role in this process. Interleukin 17 is an inflammatory cytokine, mainly by activating the memory of CD4+T lymph nodes. The cell secreted, IL - 17, binding to their receptors, can induce a variety of cytokines and adhesion molecules. These cytokines have different roles in different stages of hematopoietic and immune inflammatory reactions, such as stimulating the production of IL-6 and PGE-2, enhancing the response to local inflammation, and promoting the local production of the body. Chemical factors MCP-1, Gro-a, IL-8, and so on, contribute to the rapid aggregation of monocytes and neutrophils,.YKL-40 (human cartilage glycoprotein 39) is a member of the family of mammalian crustaceans, but no chitinase activity. Many cells in the human body, such as macrophages, neutrophils, synoviocytes and chondrocytes, can secrete YKL-40. Some studies have shown that YKL-40 can play a role in the degradation of extracellular matrix, inflammatory reaction, tissue reconstruction and stimulation of endothelial cell migration, and can also participate in the metastasis of malignant tumor. The secretion and expression of.YKL-40 have a great relationship with the pathological state of tissue or cell. It shows that it is in the process of the repair of inflammatory reaction and connective tissue. The purpose of this study was to investigate the expression of IL-17 and YKL-40 in the plasma of patients with chronic rhinosinusitis and to explore the possible mechanism of their involvement in the occurrence of chronic rhinosinusitis.
[research methods]
Blood sampling before operation, collected 38 cases of chronic rhinosinusitis (CRSwNP) with nasal polyps and 32 cases of chronic rhinosinusitis (CRSsNP) without nasal polyps (sodium citrate anticoagulant), 28 cases in the control group were from the healthy persons in the outpatient medical examination. The blood samples were collected after my informed consent, 2000rpm centrifugation 15 min, separation plasma, at -80 centigrade ice The contents of IL-17 and YKL-40 in plasma were detected by ELISA.
[results]
1. the plasma concentration of IL-17 in the normal control group was 1.6100 (1.2575-1.9830) pg/ml: chronic rhinosinusitis patients with IL-17 concentration 8.2483 (4.8868-10.1075) pg/ml and IL-17 8.2430 (6.2778-10.3610) pg/ml in patients with chronic nasal sinusitis (CRSwNP) with nasal polyps, and the plasma IL-17 concentration of patients with chronic rhinosinusitis (CRSsNP) without nasal polyps The expression of degree 8.2550 (4.8783-10.1650) pg/ml.IL-17 in the normal and chronic rhinosinusitis patients was significantly different (P0.05), and the expression in the CRSwNP. CRSsNP group was significantly higher than that of the normal people. It was presumed that it played an important role in the development of chronic rhinosinusitis, but there was no significant difference between the CRSwNP group and the CRSsNP group, which supported us. Chronic rhinosinusitis was divided into CRSwNP and CRSsNP.
2. the plasma YKL-40 concentration was 18.2145 (12.5878-20.8250) ng/ml in the normal control group; the plasma YKL-40 concentration of the patients with chronic rhinosinusitis was 48.0236 (35.1520-59.9180) ng/ml; the plasma YKL-40 concentration was 50.9490 (35.1373-63.4303) ng/ ml in patients with nasal polyps chronic rhinosinusitis (CRSwNP); the blood of patients with chronic rhinosinusitis (CRSsNP) was not accompanied by nasal polyps. The plasma YKL-40 concentration of 46.0765 (37.8620 ~ 55.3008) ng/ml.YKL-40 was significantly different in the normal and chronic rhinosinusitis patients (P0.05), and the expression in the CRSwNP.CRSsNP group was significantly higher than that of the normal people. It was presumed that it played an important role in the development of chronic rhinosinusitis, but there was no significant difference between the CRSwNP group and the CRSsNP group. Sex also supports our division of chronic rhinosinusitis into CRSwNP and CRSsNP..
3. assessment of the severity of the disease
The VAS score of group CRSwNP in 3.1 VAS score was 7.21 + 1.65, and there was no significant difference in symptom severity score between group CRSsNP and group CRSsNP, and group CRSsNP in group CRSsNP.
3.2 CT examination score CRSwNP group sinus CT score was 16.01 + 5.98, CRSsNP group sinus sinus CT score was 7.98 + 4.12: CRSwNP group CT score was significantly higher than that of CRSsNP group.
3.3 nasal endoscopic examination score CRSwNP group was 11.75 + 5.68, CRSsN group score was 6.27 + 3.21; CRSwNP group nasal endoscopic examination score was significantly higher than CRSsNP group.
3.4 the correlation analysis between the severity of the disease and the plasma IL-17 level showed that the sinus CT, the nasal endoscopy score was positively related to the plasma IL-17 level in the patients, and the correlation coefficient was (R respectively 0.710.64 P0.05).VAS score and the plasma IL-17 level was not related to the patient.
[Conclusion]
The expression of 1.IL-17 in normal people and patients with chronic rhinosinusitis was significantly different (P0.05). In CRSwNP, the expression in group CRSsNP was significantly higher than that of normal people. It was presumed that it played an important role in the development of chronic rhinosinusitis, but there was no significant difference between the CRSwNP group and the CRSsNP group, supporting us to divide the chronic rhinosinusitis from the chronic rhinosinusitis. For CRSwNP and CRSsNP.
The expression of 2.YKL-40 in normal people and patients with chronic rhinosinusitis was significantly different (P0.05). In CRSwNP, the expression in group CRSsNP was significantly higher than that of normal people. It was presumed that it played an important role in the development of chronic rhinosinusitis, but there was no significant difference between the CRSwNP group and the CRSsNP group, and it also supported us to delimit chronic rhinosinusitis. It is divided into CRSwNP and CRSsNP.
3.IL-17 and YKL-40 play an important role in the pathogenesis of chronic rhinosinusitis, and there may be some synergistic effects, but the mechanism of synergism and the relationship between them need to be further studied.
4. in evaluating the severity of the disease, there was no significant difference in the symptom severity score between the CRSwNP group and the CRSsNP group, while the CT score and the nasal endoscopy score of the CRSwNP group were all higher than those in the CRSsNP group, indicating that CRSwNP had a more severe and extensive mucosal lesion.
[research significance]
For patients with chronic rhinosinusitis, IL-17 and YKL-40 play an important role in their development, so it is possible to consider ways to reduce their content or block their effects, such as open sinus full drainage, surgical removal of polyps, and control of infection and the reduction of IL-17 and YKL-40 expression factors, or Use IL-17R, YKL-40R blocker to block its effect.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R765

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