人尿激肽原酶联合血小板抑制剂对高血压脑梗死大鼠凝血功能及神经功能的影响

Effect of human urine kallikrein combined with platelet inhibitor on coagulation function and nerve function of hypertensive rats with cerebral infarction

目的观察人尿激肽原酶联合血小板抑制剂对高血压脑梗死大鼠凝血功能及神经功能的影响。方法选择40只SD雄性大鼠作为研究对象，分为假手术组、模型组、阿司匹林组以及联合干预组；模型组、阿司匹林组以及联合干预组建立高血压脑梗死模型，阿司匹林组给予阿司匹林干预，联合干预组给予尤瑞克林、阿司匹林干预，干预7d比较4组观察炎性因子、神经功能、凝血功能。结果炎性因子：模型组血清肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）含量明显高于假手术组[（16．58±1．35）比（6．56±0．78）ng／ml，（1．14±0．28）比（0．38±0．08）ng／ml，（426．35±56．12）比（144．12±18．36）ng／ml，阿司匹林组、联合干预组明显低于模型组[（11．32±1．12）比（7．36±1．01）比（16．58±1．35）ng／ml，（0．62±0．12）比（0．47±0．06）比（1．14±0．28）ng／ml，（245．36±25．42）比（171．32±21．35）比（426．35±56．12）ng／ml]，联合干预组明显低于阿司匹林组[（7．36±1．01）比（11．32±1．12）ng／ml，（0．47±0．06）比（0．62±0．12）ng／ml，（171．32±21．35）比（245．36±25．42）ng／m1]（P〈0．05）；神经功能：模型组大鼠的神经功能评分明显高于假手术组[（2．84±0．31）分比（0．00±0．00）分]，阿司匹林组和联合干预组的神经功能评分均低于模型组[（2．07±0．22）分比（1．46±0．17）分比（2．84±0．31）分]，联合干预组的神经功能评分低于阿司匹林组[（1．46±0．17）分比（2．07±0．22）分，P〈0．05]；氧自由基：模型组超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—Px）明显低于假手术组，丙二醛（NDA）明显高于假手术组[（351．45±20．03）比（465．32±25．36）U／ml，226．25±16．45比330．21±20．32，（9．78±0．85）比（5．85±0．54）mmol／m1]；阿司匹林组、联合干预组SOD、GSH-Px明显高于模型组，MDA明显低于模型组[（413．12±20．36）比（445．68±21．32）比（351．45±20．03）U／ml，278．36±22．45比325．64±21．45比226．25±16．45，（8．12±0．78）比（6．22±0．7）比（9．78±0．85）mmol／ml]；联合干预组SOD、GSH—Px明显高于阿司匹林组，MDA明显低于阿司匹林组[（445．68±21．32）比（413．12±20．36）U／ml，325．64±21．45比278．36±22．45，（6．22±0．74）比（8．12±0．78）mmol／ml]（P〈0．05）；凝血功能：模型组大鼠D-二聚体（D—D）、纤维蛋白原（Fib）、血小板黏附率、血小板聚集率均明显高于假手术组[（0．65．±0．21）比（0．36±0．12）mg/L，（183．25±34．25）比（121．32±18．32）mg／dl，（37．68±4．48）％比（19．58±2．24）％，（77．68±8．96）％比（28．68±3．48）％]，阿司匹林组和联合干预组明显低于模型组[（0．52±0．24）比（0．43±0．18）比（0．65±0．21）mg／L，（145．32．±16．25）比（128．56±14．32）比（183．25±34．25）mg／dl，（21．58±2．85）％比（14．85±1．76）％比（37．68±4．48）％，（35．67±3．86）％比（21．58±2．86）％比（77．68±8．96）％]，联合干预组明显低于阿司匹林组[（0．52±0．24）比（0．43±0．18）mg／L，（145．32±16．25）比（128．56±14．32）mg／dl，（21．58±2．85）％比（14．85±1．76）％，35．67±3．86比21．58±2．86]（P〈0．05）。结论人尿激肽原酶联合血小板抑制剂有助于缓解高血压脑梗死大鼠炎症状态，改善凝血功能及神经功能。

Objective To study the effect of human urine kallikrein combined with platelet inhibitor on coagulation function and nerve function of hypertensive rats with cerebral infarction. Methods SD mule rats were divided into sham- operated group, model group, aspirin group, and combination interven- tion group. Hypertension infarction model was established in model group, aspirin group, and combination intervention group. Aspirin group was given aspirin intervention, combination intervention group was given Uuribe Brooklyn and aspirin intervention. After intervention for 7 days, inflammatory factor, neural func- tion, and coagulation function were compared among four groups. Results Serum tumor necrosis factor-α （TNF- α）, intercellular adhesion molecule - 1 （ICAM - 1 ）, and vascular cell adhesion molecule - 1 （ VCAM - 1 ） levels in model group were significantly higher than the sham group [ （ 16. 58 ± 1.35 ） vs. （6. 56 ± 0.78） ng/ml, （1.14±0.28） vs. （0.38±0.08） ng/ml, and （426.35±56.12） vs. （144.12±18.36） ng/ml], those in aspirin group, and combination intervention group were significantly lower than those in model group [（11.32±1.12） vs. （7.36±1.01）vs. （16.58±1.35）ng/ml, （0.62±0.12）vs. （0.47±0.06）vs. （1.14± 0. 28） ng/ml, and （245. 36 ±25.42） vs. （171.32 ±21.35） vs. （426. 35 ±56. 12） ng/ml], and those in combi- nation intervention group were lower than those in aspirin group [ （7. 36 ± 1.01 ） vs. （ 11.32 ± 1.12） ng/ml, （0.47±0.06） vs. （0.62±0.12） ng/ml, and （171.32±21.35） vs. （245.36±25.42） ng/ml] （P〈0.05）. Nerve function scores in model group were significantly higher than those in sham group （2. 84 ±0. 31 vs. 0. 00 ± 0. 00）, those in aspirin group and combination intervention group were lower than those in model group （2.07 ±0. 22 vs. 1.46 ±0. 17 vs. 2. 84 ±0. 31 ）, and those in combination intervention group were lower than those in aspirin group （ 1.46 ± 0. 17 vs. 2.07 ± 0. 22 ） （ P 〈 0. 05 ）. Superoxide dismutase （SOD）, and glutathione peroxidasc （GSH- Px） in model group were significantly lower than those in sham group, and mulondialdehyde （MDA） level was significantly higher than in control group [ （351.45 ± 20.03） vs. （465.32±25.36） U/ml, （226.25±16.45） vs. （330.21 ±20.32）, and （9.78±0.85） vs. （5.85± 0. 54） mmol/ml]. SOD, and GSH- Px levels in aspirin group and combination intervention group were signifi- candy higher than those in model group, and MDA level was significantly lower than in model group [（413.12±20.56） vs. （445.68±21.32） vs. （351.45±20.03） U/ml, 278.36±22.45 vs. 325.64±21.45 vs. 226.25±16.45, and （8.12±0.78） vs. （6.22±0.74） vs. （9.78±0.85） mmol/ml] SOD, and GSH-Px lev- els in combination intervention group were significantly higher than those in aspirin group, and the MDA level was signifcanfly lower than in aspirin group [（445.68 ±21.32） vs. （413. 12 ±20.36） U/ml, （325.64 ± 21.45） vs. （278.36±22.45）, and （6.22±0.74） vs. （8.12±0.78） mrnol/ml] （P〈0.05）. D-dimer （D- D） and fibrinogen （Fib） levels, and platelet adhesion rate and platelet aggregation rate in model group were significantly higher than those in sham group [ （0.65 ±0. 21） vs. （0. 36 ±0. 12） nag/L, （183. 25 ±34. 25） vs. （121.32±18.32） mg/dl, （37.68±4.48）% vs. （19.58±2.24）%, and （77.68 ±8.96）% vs. （28. 68 ± 3.48 ） % ], those in aspirin group and combination intervention group were significantly lower than in model group [ （0. 52 ±0. 24） vs. （0. 43 ± 0. 18 ） vs. （0. 65 ± 0. 21 ） mg/L, （ 145.32 ± 16. 25 ） vs. （128.56±14.32） vs. （183.25 ±34.25） mg/dl, （21.58 ±2.85）% vs. （14.85±1.76）% vs. （37. 68 ± 4. 48） %, and （35.67 ± 3.86） % vs. （21.58 ± 2. 86 ） % vs. （77. 68 ± 8. 96） % ], and those in combination intervention group were significantly lower than those in aspirin group [ （0. 52 ± 0. 24） vs. （0.43 ±0.18） mg/L, （145.32 ± 16.25） vs. （128.56 ± 14.32） mg/dl, （21.58 ±2.85）% vs. （14.85 ±1.76）%, and 35.67 ±3.86 vs. 21.58 ±2.86, P〈0.05]. Conclusion Human urine kul- likrein combined with platelet inhibitors help to ease inflammatory state in rats with hypertensive cerebral infarction, and improve blood clotting function and nerve function.