血管内皮生长因子、内皮抑素及热休克蛋白60、70与川崎病冠脉损害的关系

发布时间：2018-06-21 04:39

本文选题：血管内皮生长因子 + 内皮抑素　；参考：《泸州医学院》2012年硕士论文

【摘要】：目的：研究川崎病(KD)患儿在急性期及恢复期血中血管内皮生长因子（VEGF）、内皮抑素（ES）、热休克蛋白60（HSP60）及热休克蛋白70（HSP70）的表达水平，探讨KD急性期与恢复期血清中VEGF与ES的相关性分析研究，并研究其表达对KD冠脉损害的影响，进而为研究及预防冠脉损害提供相应的理论依据。方法：1.标本采集：（1）研究组：KD患儿25例，其中冠脉损害组（CAL）10例，冠脉正常组（NCAL）15例，分别采集急性期（静脉使用IVIG前，病程1-2周）、恢复期（静脉使用IVIG后，病程3-4周）外周血制备血清。（2）对照组：分别采集20例年龄相仿的正常健康患儿（空白对照组，C组）及20例年龄相仿的发热患儿（发热对照组，F组）外周血制备血清。 2.指标检测：分别用双抗体夹心法（ELISA）测定各组血管内皮生长因子（VEGF）、内皮抑素（ES）、热休克蛋白60（HSP60）及热休克蛋白70（HSP70）的表达水平。 3.统计学处理：运用SPSS17.0行统计学分析，数据都采取以均数加减标准差（X+S）表示。组间比较用单因素方差分析(one-way analysisof variance，ANOVA)，两两比较采用LSD检验；VEGF/ES比值用秩和检验。VEGF与ES的相关性分析采用Bivariate法，，检验水准为0.05（双侧），P0.05为差异有统计学意义。结果：1.VEGF、ES、VEGF/ES （1）KD急性期血清VEGF（1123.82±80.31）水平与KD恢复期（586.65±78.38）、发热对照组（306.43±67.92）和空白对照组（244.65±69.10）相比明显升高（P均0.01）；KD恢复期血清VEGF（586.65±78.38）水平与发热对照组（306.43±67.92）和空白对照组（244.65±69.10）相比明显升高（P均0.01）。（2）KD急性期血清ES水平（173.23±5.41）与发热对照组（188.17±5.25）相比明显降低（P0.05）；和空白对照组（195.30±5.84）相比明显降低（P0.01）；与KD恢复期（180.44±6.03）相比较，无明显统计学意义（P0.05）。（3）KD恢复期血清ES水平（180.44±6.03）与发热对照组（188.17±5.25）和空白对照组（195.30±5.84）相比明显降低（P均0.05）。（4）KD急性期血清VEGF/ES（6.89±1.02×10~(-3)）与KD恢复期（3.95±0.76×10~(-3)）、发热对照组（1.64±0.20×10~(-3)）和空白对照组（1.26±0.18×10~(-3)）相比明显升高（P均0.01）；KD恢复期VEGF/ES（3.95±0.76×10~(-3)）与发热对照组（1.64±0.20×10~(-3)）和空白对照组（1.26±0.18×10~(-3)）相比明显升高（P均0.01）。（5）发热对照组血清VEGF（306.43±67.92）、ES（188.17±5.25）、VEGF/ES（1.64±0.20×10~(-3)）与空白对照组相比VEGF（244.65±69.10）、ES（195.30±5.84）、VEGF/ES（1.26±0.18×10~(-3)），无明显统计学意义（P均0.05）。（6）川崎病CAL组血清VEGF （1260.23±82.65）、 VEGF/ES（6.91±0.88×10~(-3)）和NCAL组血清VEGF（976.54±76.30）、VEGF/ES（4.12±0.65×10~(-3)）相比较明显增高（P均0.01）；川崎病CAL组血清ES水平（168.42±8.40）和NCAL组（188.54±7.85）相比较明显降低，差异有统计学意义（P0.01）。 2.VEGF与ES的相关性分析 KD急性期血清VEGF与ES呈显著性负相关（r=-0.642，P0.01）；KD恢复期血清VEGF与ES呈显著性负相关（r=-0.806，P0.01）。 3. HSP60、HSP70 （1）KD急性期血清HSP60水平（4557.30±432.71）与KD恢复期（3987.43±378.95）、发热对照组（3894.50±564.33）、空白对照组（3871.23±489.40）相比较明显增高（P均0.01）。（2）KD急性期血清HSP70水平（4633.28±679.33）较KD恢复期（4027.14±595.25）、发热对照组（3410.15±674.10）、空白对照组（3396.50±639.23）明显增高（P均0.01）。（3）KD恢复期血清HSP60（3987.43±378.95）与发热对照组（3894.50±564.33）、空白对照组（3871.23±489.40）相比较，差异无明显统计学意义（P均0.05）。（4）KD恢复期血清HSP70（4027.14±595.25）与发热对照组（3410.15±674.10）、空白对照组（3396.50±639.23）相比较明显增高，差异有统计学意义（P均0.01）。（5）发热对照组HSP60（3894.50±564.33）、HSP70（3410.15±674.10）和空白对照组HSP60（3871.23±489.40）、HSP70（3396.50±639.23）相比较，无明显统计学意义（P均0.05）（。6）KD患儿CAL组血清HSP60（4779.34±564.31）较NCAL组（3874.27±478.37）明显增高，差异有统计学意义（P0.01）；KD患儿CAL组血清HSP70（3569.37±603.34）较NCAL组（4899.40±637.21）明显降低，差异有统计学意义（P0.05）。结论：1.在KD急性期中血清VEGF、VEGF/ES明显升高，而恢复期二者虽有所下降，但仍处于一个相对高的水平；而急性期血清ES水平明显降低，在恢复期血清ES水平仍处于一个低水平。川崎病CAL组血清VEGF、VEGF/ES较NCAL组相比均明显增高；川崎病CAL组血清ES水平较NCAL组相比明显降低。提示VEGF、ES不仅参与了KD早期血管炎症过程，而且高水平的VEGF、VEGF/ES可能参与了KD中持久的冠脉损伤。 VEGF、VEGF/ES可作为川崎病冠脉损害的危险因素之一，在KD血管壁的损伤与冠脉瘤的形成中起重要作用，而ES在病程中起到抑制血管炎性反应的作用。 2.血清VEGF与ES在KD急性期、恢复期均呈显著性负相关（r=-0.642，P0.01；r=-0.806，P0.01）。提示ES在KD病程能够在一定程度上抑制VEGF的作用，起到抑制冠脉损害的功能；VEGF与ES之间的平衡参与了KD血管壁的重构。 3. KD急性期患儿血清HSP60、HSP70水平明显增高，而恢复期血清HSP60显著下降，HSP70仍维持在一个高水平。KD患儿CAL组血清HSP60水平显著较NCAL组高，而CAL组血清HSP70水平显著较NCAL组低，提示在冠脉损害发生情况中，HSP60是作为一个危险因素存在，可能与“抗原模拟宿主学说”有关;热休克蛋白70在冠脉损害过程中，可能起保护作用，抑制血管炎性反应的发生。急性期高水平的HSP60、HSP70提示二者在KD急性期中均积极的参与了血管炎性反应，HSP60促进血管炎性反应，而HSP70起了抑制作用；恢复期HSP70仍维持在一个高水平，提示HSP70对血管炎性反应的抑制可以持续到病程的恢复期。
[Abstract]:Objective : To investigate the expression level of vascular endothelial growth factor ( VEGF ) , endothelin ( ES ) , heat shock protein 60 ( HSP60 ) and heat shock protein 70 ( HSP70 ) in children with KD .

Methods : 1 . Specimens were collected : ( 1 ) study group : 25 patients with KD , 10 patients with coronary lesion group ( CAL ) and 15 normal controls ( NCAL ) .

2 . Target detection : The expression levels of VEGF , ES , HSP60 and HSP70 were determined by ELISA .

3 . Statistical treatment : SPSS 17.0 was used to analyze the statistical analysis . The data was expressed by mean addition and subtraction standard deviation ( X + S ) . One - way ANOVA of variance ( ANOVA ) was used to compare the two comparisons .
The correlation analysis of VEGF and ES showed that the level of VEGF and ES was 0.05 ( bilateral ) and P 0.05 was statistically significant .

Results : 1 . VEGF , ES , VEGF / ES

( 1 ) The serum VEGF ( 1123 . 82 卤 80.31 ) levels in KD acute phase were significantly higher than those in KD recovery period ( 586.65 卤 78.38 ) , fever group ( 306.43 卤 67.92 ) and blank control group ( 244.65 卤 69.10 ) ( P < 0.01 ) .
The serum levels of VEGF ( 586.65 卤 78.38 ) in KD recovery period were significantly higher than that in the control group ( 306.43 卤 67.92 ) and the control group ( 244.65 卤 69.10 ) ( P < 0.01 ) .
Compared with the blank control group ( 195.30 卤 5.84 ) , there was a significant decrease ( P0.01 ) .
( 4 ) The serum VEGF / ES ( 6.89 卤 1.02 脳 10 ~ ( -3 )) and KD recovery period ( 3.95 卤 0.76 脳 10 ~ ( -3 )) and the control group ( 1.26 卤 0.18 脳 10 ~ ( -3 )) were significantly higher than those in the control group ( 1.64 卤 0.20 脳 10 ~ ( -3 )) and the control group ( 1.26 卤 0.18 脳 10 ~ ( -3 )) ( P < 0.01 ) .
VEGF / ES ( 3.95 卤 0.76 脳 10 ~ ( -3 )) in KD recovery period was significantly higher than that in control group ( 1.64 卤 0.20 脳 10 ~ ( -3 )) and blank control group ( 1.26 卤 0.18 脳 10 ~ ( -3 )) . The serum VEGF ( 126.23 卤 82.65 ) , VEGF / ES ( 6.91 卤 0.88 脳 10 ~ ( -3 )) , VEGF / ES ( 6.91 卤 0.88 脳 10 ~ ( -3 )) and VEGF / ES ( 4.12 卤 0.65 脳 10 ~ ( -3 )) were significantly higher than those in control group ( P < 0.01 ) .
The serum ES level ( 168.42 卤 8.40 ) and the NCAL group ( 188.54 卤 7.85 ) decreased significantly in the CAL group of Kawasaki disease ( P0.01 ) .

2 . Correlation between VEGF and ES

There was a negative correlation between serum VEGF and ES in KD acute phase ( r = - 0.642 , P0.01 ) .
There was a significant negative correlation between serum VEGF and ES in KD recovery period ( r = - 0.806 , P0.01 ) .

3. HSP60,HSP70

( 3 ) The serum HSP60 ( 3987.43 卤 375.25 ) and the control group ( 3871.23 卤 489.40 ) and the control group ( 3871.23 卤 489.40 ) were significantly higher than those in the control group ( 3894.50 卤 564.33 ) and the control group ( 3871.23 卤 489.40 ) . The serum HSP60 ( 4779.34 卤 564.31 ) in the KD recovery period was significantly higher than that in the control group ( 3874.27 卤 474.31 ) .
Compared with the NCAL group ( 4899.40 卤 637.21 ) , the serum HSP70 ( 3569.37 卤 603.34 ) decreased significantly in the CAL group ( P0.05 ) .

Conclusion : 1 . Serum VEGF and VEGF / ES increased significantly in the acute phase of KD , while the recovery period decreased , but remained at a relatively high level .
The serum ES level in the acute phase was significantly lower than that in NCAL group , but the serum ES level was still at a low level during the recovery period .
The levels of serum ES in patients with Kawasaki disease were significantly lower than those in NCAL group , suggesting that VEGF and ES were not only involved in the early stage of vascular inflammation in KD , but VEGF and VEGF / ES might participate in the long - lasting coronary artery injury in KD . Vascular endothelial growth factor ( VEGF ) and VEGF / ES play an important role in the pathogenesis of Kawasaki disease .

2 . There was a significant negative correlation between serum VEGF and ES in KD acute stage and recovery period ( r = - 0.642 , P0.01 ) .
r=-0.806,P0.01). It is suggested that ES can inhibit VEGF to some extent in KD course , and play a role in inhibiting coronary lesion ;
The equilibrium between VEGF and ES is involved in the reconstruction of the KD vessel wall .

The levels of HSP60 and HSP70 in serum HSP60 and HSP70 in children with KD were significantly higher than those in NCAL group , but the level of HSP70 in CAL group was significantly lower than that in NCAL group .
HSP70 was maintained at a high level during the recovery period , suggesting that the inhibition of HSP70 on vascular inflammatory response can persist to the recovery period of the course .
【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.4

【参考文献】