尤瑞克林对急性脑梗死患者血浆HMGB1、MMP-9和TIMP-1水平的影响

发布时间：2018-05-07 11:55

本文选题：尤瑞克林 + 急性脑梗死　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:急性脑梗死是神经系统常见的急症之一,其引起的神经功能缺损严重影响着患者的日常生活。脑缺血后,细胞氧化代谢中断,神经元线粒体功能障碍,能量产生不足,微血管受损,随后,神经炎性级联反应被激活,导致脑损伤进一步加重。其中血脑屏障(blood-brain barrier,BBB)通透性的改变在急性脑梗死中发挥了关键作用。本实验通过观察急性脑梗死患者血浆中高迁移率族蛋白B1(high mobility group box 1,HMGB1)、基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、基质金属蛋白酶组织抑制剂1(tissue inhibitor of matrix metalloproteinase-1,TIMP-1)在不同时期的浓度变化,研究尤瑞克林对血脑屏障的保护作用,并探讨其中可能的机制。方法:1收集2015年1月至2015年10月期间河北医科大学第二医院神经内科收治的首次发病的急性脑梗死病人100例。随机分为尤瑞克林组和常规治疗组。2分别对两组患者在入院后第1天、14天和3月时进行NHISS评分。并抽取第1天和第14天的空腹静脉血5ml,用酶联免疫吸附法检测血浆中HMGB1,MMP-9,TIMP-1的浓度。结果:1研究对象分布:本实验共纳入100例急性脑梗死患者,均符合入组标准,随机分为两组,每组各50例,但由于病情变化和患者依从性差等情况共计22例患者脱组,最终共纳入尤瑞克林组45例,常规治疗组33例。2基线资料比较:两组患者在年龄、性别、文化程度、用药前的NHISS评分等方面均无统计学差异(P0.05),两组患者具有可比性。3临床疗效评价:入院第1天,尤瑞克林组及常规治疗组的NHISS评分无统计学差异(P0.05);随访3个月,两组的NHISS评分均进行性下降,并且在入院14天及3个月时,两组的NHISS评分均有统计学差异(P0.05)。4血浆MMP-9含量的测定:两组患者MMP-9含量在入院1天时相比无统计学差异(P0.05),而在14天时有统计学差异(P0.05)。与入院1天时相比,尤瑞克林组患者血浆MMP-9的水平在14天时有明显的下降(P0.05)。而常规治疗组则无明显的变化(P0.05)。5血浆TIMP-1含量的测定:两组在入院第1天时相比无统计学差异(P0.05);在入院后14天相比仍无统计学差异(P0.05)。随着病程的进展,与入院1天时相比,两组患者血浆中TIMP-1的含量在14天时均明显升高(P0.05)。且在入院后14天时包括两组患者在内的观察总体TIMP-1水平与入院第1天时相比也有显著的统计学差异(P0.05)。6血浆HMGB1含量的测定:两组在住院1天时相比无统计学差异(P0.05),在入院14天时相比有统计学差异(P0.05)。随着病程的进展,尤瑞克林组患者血浆中HMGB1含量在14天时比入院1天时有明显的下降(P0.05)。而常规治疗组中患者HMGB1含量并无明显的改变(P0.05)。7血浆TIMP-1、MMP-9相关性的测定:入院第1天测得的观察病人总体的TIMP-1与MMP-9具有正相关性(P0.05,r=0.277),而在入院14天,TIMP-1和MMP-9不具有相关性(P0.05)。8血浆HMGB1、MMP-9相关性测定:入院第1天测得的观察病人总体的HMGB1与MMP-9不具有相关性(P0.05),而在入院后14天测得的HMGB1与MMP-9具有正相关性(P0.05,r=0.276)。结论:1尤瑞克林能够显著改善急性脑梗死患者的近期及远期神经功能评分。2尤瑞克林能够降低血浆MMP-9和HMGB1的水平,而对TIMP-1的影响并不大。3尤瑞克林可能通过降低血浆MMP-9、HMGB1的水平,从而保护血脑屏障、减轻脑损伤。
[Abstract]:Objective: acute cerebral infarction is one of the most common acute neuropathy in the nervous system. The impairment of nerve function seriously affects the daily life of the patients. After cerebral ischemia, cell oxidative metabolism interrupts, neuron mitochondrial dysfunction, energy production deficiency, microvascular damage, then the neuroinflammatory cascade is activated, leading to further brain damage. The changes in the permeability of blood-brain barrier (BBB) have played a key role in acute cerebral infarction. In this experiment, the high mobility group protein B1 (high mobility group box 1, HMGB1), matrix metalloproteinase 9 (matrix metalloproteinase 9, MMP-9), matrix metalloproteinase group were observed in the patients with acute cerebral infarction. The changes in the concentration of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) at different periods were used to study the protective effect of Yuri klin on the blood brain barrier and to explore the possible mechanisms. Methods: 1 the acute onset of the first onset of the neurology department of the second hospital of Hebei Medical University from January 2015 to October 2015 was collected. 100 patients with cerebral infarction were randomly divided into the Yuri klin group and the routine treatment group (.2). The two groups were divided into two groups at first days, 14 days and March respectively. The fasting venous blood 5ml of first days and fourteenth days was extracted. The concentration of HMGB1, MMP-9 and TIMP-1 in plasma was detected by enzyme linked immunosorbent assay. Results: 1 subjects were distributed: this experiment was in total 100 cases of acute cerebral infarction were in accordance with the standard of entry group, which were randomly divided into two groups, 50 cases in each group, but 22 patients were removed from the group because of the change of the condition and the poor compliance of the patients. Finally, 45 cases were included in the Yuri klin group. The baseline data of 33 cases of.2 in the routine treatment group were compared: the two groups were in age, sex, educational level, NHI before medication. There was no statistical difference in the SS score (P0.05). The two groups had comparable clinical efficacy evaluation of.3: the NHISS score of the Yuri klin group and the conventional treatment group was not statistically significant (P0.05) at first days of admission; the two groups were followed up for 3 months, and the two groups of NHISS scores were all in the 14 and 3 months. P0.05.4 plasma MMP-9 content determination: the MMP-9 content in the two groups was not statistically significant at 1 days (P0.05), but there was a statistical difference at 14 days (P0.05). The plasma MMP-9 level of the Yuri klin group was significantly decreased at 14 days (P0.05), but there was no significant change in the conventional treatment group. (P0.05).5 plasma TIMP-1 content: there was no statistical difference between the two groups at first days (P0.05), and there was no statistical difference between the 14 days after admission (P0.05). With the progression of the hospital, the level of TIMP-1 in the plasma of the two groups increased significantly (P0.05) at 14 days compared with the admission process (P0.05), and included two groups at 14 days after admission. The total TIMP-1 level, compared with the first days of admission, was also significantly different (P0.05).6 plasma HMGB1 content determination: there was no statistical difference between the two groups at 1 days of hospitalization (P0.05), and there was a statistically significant difference (P0.05) at the time of admission (P0.05). The plasma HMGB1 content of the Yuri klin group was 14 along with the progression of the disease. The day time was significantly lower than that at 1 days (P0.05). But there was no significant change in the content of HMGB1 in the routine treatment group (P0.05).7 plasma TIMP-1, MMP-9 correlation: the overall TIMP-1 and MMP-9 had a positive correlation (P0.05, r= 0.277) on the first day of admission (P0.05, r= 0.277), while TIMP-1 was not associated with MMP-9 in the hospital (14 days). 5).8 plasma HMGB1, MMP-9 correlation determination: the total HMGB1 of the observed patients at the first day of admission was not associated with MMP-9 (P0.05), and the HMGB1 and MMP-9 measured on the 14 day after admission (P0.05, r=0.276). Conclusion: 1 Yuri Clin can significantly improve the short-term and long term neurological function score of patients with acute cerebral infarction,.2 Yuri Colin can reduce the level of plasma MMP-9 and HMGB1, but the effect on TIMP-1 is not.3 Yuri Colin may reduce the level of plasma MMP-9, HMGB1, thus protecting the blood brain barrier and alleviating brain damage.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3

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