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脑梗死是成人最常见的致死疾病,急性缺血性脑梗死占脑梗死的1/3~1/4,积极治疗急性缺血性脑梗死对改善病人预后、降低死亡率具有重要意义[1]。早期及时对急性脑梗死病人进行溶栓治疗可以使阻塞的脑血管再通、脑组织局部血液灌流恢复、梗死体积减少、神经功能缺损改善,是唯一有效的治疗急性脑梗死的手段[2]。重组组织型纤溶酶原激活剂(recombinant tissue-type plasminogen activator,r-tPA)是美国FDA唯一认可的早期溶栓治疗急性缺血性脑梗死的药物,其静脉使用的安全有效的时间为急性缺血性脑梗死后4.5 h内[3-5],r-tPA对急性缺血性脑梗死4.5 h后的超时间窗病人的治疗效果尚需进一步研究。本文对血栓性大脑中动脉栓塞大鼠r-tPA超时间窗静脉溶栓的治疗效果进行研究,旨在为临床提供依据。
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4.5 h溶栓组和6 h溶栓组3 d及7 d脑梗死体积均显著低于脑梗死组(P < 0.01),6 h溶栓组3 d及7 d脑梗死体积与4.5 h溶栓组差异无统计学意义(P>0.05)。各组内3 d和7 d的脑梗死体积差异均无统计学意义(P>0.05)(见表 1)。
分组 n 3 d 7 d t P 脑梗死组 9 92.14±11.36 94.52±12.17 0.43 >0.05 4.5 h溶栓组 8 64.67±7.83** 72.47±10.36** 1.70 >0.05 6 h溶栓组 8 67.54±8.92** 75.35±9.78** 1.67 >0.05 F — 21.46 10.47 — — P — <0.01 <0.01 — — MS组内 — 91.751 118.442 — — q检验:与脑梗死组比较**P < 0.01 表 1 各组大鼠脑梗死体积比较(x±s;%)
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4.5 h溶栓组和6 h溶栓组3 d及7 d脑微血管密度均显著高于脑梗死组(P < 0.01),6 h溶栓组3 d及7 d脑微血管密度均低于4.5 h溶栓组(P < 0.05)。4.5 h和6 h溶栓组的7 d脑微血管密度均显著高于3 d脑微血管密度(P < 0.01)(见表 2)。
分组 n 3 d 7 d t P 脑梗死组 9 13.24±1.43 14.37±1.26 1.78 >0.05 4.5 h溶栓组 8 24.58±1.87** 29.73±2.02**▲▲ 5.29 < 0.01 6 h溶栓组 8 22.53±1.92**# 27.38±1.78**#▲▲ 5.24 < 0.01 F — 103.93 204.78 — — P — <0.01 <0.01 — — MS组内 — 3.029 2.884 — — q检验:与脑梗死组比较**P < 0.01;与4.5 h溶栓组比较#P < 0.05;组内与3 d比较▲▲P < 0.01 表 2 各组大鼠脑微血管密度比较(x±s)
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对照组组、4.5 h溶栓组、6 h溶栓组大鼠3 d和7 d皮层脑组织NO含量、MDA含量均显著低于脑梗死组,SOD活性显著高于脑梗死组(P < 0.05~P < 0.01);6 h溶栓组3 d和7 d皮层脑组织MDA含量高于4.5 h溶栓组(P < 0.05~P < 0.01),6 h溶栓组3 d和7 d皮层脑组织SOD含量低于4.5 h溶栓组(P < 0.05);4.5 h溶栓组和6 h溶栓组大鼠7 d皮层脑组织NO含量高于3 d NO含量(P < 0.05),4.5 h溶栓组和6 h溶栓组大鼠3 d和7 d皮层脑组织MDA含量、SOD活性比较差异无统计学意义(P>0.05)(见表 3)。
分组 n NO含量/(μmol/mgprot) MDA含量/(nmol/mgprot) SOD活性/(U/mgprot) 3 d 7 d 3 d 7 d 3 d 7 d 对照组 10 0.62±0.11** 0.65±0.13** 4.72±0.48** 4.83±0.52** 142.15±25.36** 144.35±23.14** 脑梗死组 9 1.68±0.23 1.95±0.21▲ 24.35±11.28 27.52±12.47 93.24±21.54 95.47±22.31 4.5 h溶栓组 8 1.12±0.16** 1.34±0.19**▲ 13.27±5.38* 17.46±5.83** 118.79±20.98* 121.42±18.79* 6 h溶栓组 8 1.22±0.24** 1.42±0.23**▲ 14.43±6.02*# 19.78±6.31**# 115.46±19.83*# 117.38±19.03*# F — 49.90 74.61 12.82 14.89 7.69 8.54 P — <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 MS组内 — 0.036 0.036 47.622 56.873 494.634 445.402 q检验:与脑梗死组比较*P < 0.05,**P < 0.01;与4.5 h溶栓组比较#P < 0.05,##P < 0.01;组内与3 d比较▲P < 0.05 表 3 各组大鼠皮层脑组织NO、MDA水平及SOD活性比较(x±s)
超时间窗静脉溶栓对大鼠血栓性大脑中动脉栓塞的治疗效果及机制探讨
Therapeutic effect and mechanism of super time window venous thrombolysis on thromboembolic middle cerebral artery occlusion in rats
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摘要:
目的探讨超时间窗静脉溶栓对血栓性大脑中动脉栓塞大鼠的治疗效果。 方法80只SD大鼠根据随机数字法分为对照组、脑梗死组、4.5 h溶栓组和6 h溶栓组,每组20只。对照组进行假手术处理,脑梗死组、4.5 h溶栓组和6 h溶栓组大鼠均建立大脑中动脉栓塞模型,4.5 h溶栓组和6 h溶栓组大鼠建模后分别于4.5 h、6 h给予重组组织型纤溶酶原激活剂(r-tPA)静脉泵入处理。测定各组大鼠脑梗死体积、微血管密度及皮层脑组织一氧化氮(NO)、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性。 结果4.5 h溶栓组和6 h溶栓组3 d及7 d脑梗死体积均显著低于脑梗死组(P < 0.01)。4.5 h溶栓组和6 h溶栓组3 d及7 d脑微血管密度均显著高于脑梗死组(P < 0.01),6 h溶栓组3 d及7 d脑微血管密度均低于4.5 h溶栓组(P < 0.05)。4.5 h和6 h溶栓组的7 d脑微血管密度均显著高于3 d脑微血管密度(P < 0.01)。与脑梗死组比较,对照组、4.5 h溶栓组、6 h溶栓组大鼠3 d和7 d皮层脑组织NO和MDA含量均明显降低,而SOD显著升高(P < 0.05~P < 0.01),6 h溶栓组3 d和7 d皮层脑组织MDA含量高于4.5 h溶栓组(P < 0.05~P < 0.01),6 h溶栓组3 d和7 d皮层脑组织SOD含量低于4.5 h溶栓组(P < 0.05);4.5 h溶栓组和6 h溶栓组大鼠7 d皮层脑组织NO含量高于3 d NO含量(P < 0.05)。 结论超时间窗静脉溶栓治疗可降低血栓性大脑中动脉栓塞大鼠的梗死体积,其机制可能与其可增加微血管密度及降低皮层脑组织NO含量和MDA含量、升高皮层脑组织SOD活性有关。 -
关键词:
- 脑梗死 /
- 超时间窗 /
- 静脉溶栓 /
- 血栓性大脑中动脉栓塞 /
- 大鼠
Abstract:ObjectiveTo investigate the effects of super time window venous thrombolysis on thrombotic middle cerebral artery occlusion in rats. MethodsEighty rats were divided into the control group, cerebral infarction group, 4.5 h thrombolysis group and 6 h thrombolysis group according to random number method(20 rats each group).The control group rats were treated with the sham operation, and the middle cerebral artery occlusion model was established in cerebral infarction group, 4.5 h thrombolysis group and 6 h thrombolysis group.The 4.5 h thrombolysis group and 6 h thrombolysis group were intravenously treated with the recombinant tissue plasminogen activator(r-tPA) after 4.5 h and 6 h of modeling.The cerebral infarction volume, microvessel density, contents of nitric oxide(NO) and malondialdehyde(MDA), and activity of superoxide dismutase(SOD) in the cortical brain tissue were measured. ResultsThe volume of cerebral infarction in 4.5 h thrombolytic group and 6 h thrombolytic group on the third day and seventh day was significantly lower than that in cerebral infarction group(P < 0.01).The microvessel densities in 4.5 h thrombolytic group and 6 h thrombolytic group were significantly higher than that in cerebral infarction group(P < 0.01), and which in 6 h thrombolytic group were significantly lower than that in 4.5 h thrombolytic group on the third day and seventh day(P < 0.05).The microvessel densities in 4.5 h thrombolytic group and 6 h thrombolytic group on the seventh day were significantly higher than that on the third day(P < 0.01).Compared with the cerebral infarction group, the levels of NO and MDA significantly increased, and the SOD level significantly decreased in cortical brain tissue in control group, 4.5 h thrombolysis group and 6 h thrombolysis group on the third day and seventh day(P < 0.05 to P < 0.01).The level of MDA in cortical brain tissue in 6 h thrombolysis group was higher than that in 4.5 h thrombolysis group on the third day and seventh day(P < 0.05 to P < 0.01).The level of SOD in cortical brain tissue in 6 h thrombolysis group was lower than that in 4.5 h thrombolysis group on the third day and seventh day(P < 0.05).The levels of NO in cortical brain tissue in 4.5 h thrombolysis group and 6 h thrombolysis group on the seventh day were higher than that on the third day(P < 0.05). ConclusionsThe super time window thrombolytic therapy can reduce the infarct volume of thrombus middle cerebral artery embolization in rats, and the mechanism of which may be related to the increasing of the microvessel density, decreasing of NO and MDA contents, and increasing of SOD activity in cortical brain tissue. -
表 1 各组大鼠脑梗死体积比较(x±s;%)
分组 n 3 d 7 d t P 脑梗死组 9 92.14±11.36 94.52±12.17 0.43 >0.05 4.5 h溶栓组 8 64.67±7.83** 72.47±10.36** 1.70 >0.05 6 h溶栓组 8 67.54±8.92** 75.35±9.78** 1.67 >0.05 F — 21.46 10.47 — — P — <0.01 <0.01 — — MS组内 — 91.751 118.442 — — q检验:与脑梗死组比较**P < 0.01 表 2 各组大鼠脑微血管密度比较(x±s)
分组 n 3 d 7 d t P 脑梗死组 9 13.24±1.43 14.37±1.26 1.78 >0.05 4.5 h溶栓组 8 24.58±1.87** 29.73±2.02**▲▲ 5.29 < 0.01 6 h溶栓组 8 22.53±1.92**# 27.38±1.78**#▲▲ 5.24 < 0.01 F — 103.93 204.78 — — P — <0.01 <0.01 — — MS组内 — 3.029 2.884 — — q检验:与脑梗死组比较**P < 0.01;与4.5 h溶栓组比较#P < 0.05;组内与3 d比较▲▲P < 0.01 表 3 各组大鼠皮层脑组织NO、MDA水平及SOD活性比较(x±s)
分组 n NO含量/(μmol/mgprot) MDA含量/(nmol/mgprot) SOD活性/(U/mgprot) 3 d 7 d 3 d 7 d 3 d 7 d 对照组 10 0.62±0.11** 0.65±0.13** 4.72±0.48** 4.83±0.52** 142.15±25.36** 144.35±23.14** 脑梗死组 9 1.68±0.23 1.95±0.21▲ 24.35±11.28 27.52±12.47 93.24±21.54 95.47±22.31 4.5 h溶栓组 8 1.12±0.16** 1.34±0.19**▲ 13.27±5.38* 17.46±5.83** 118.79±20.98* 121.42±18.79* 6 h溶栓组 8 1.22±0.24** 1.42±0.23**▲ 14.43±6.02*# 19.78±6.31**# 115.46±19.83*# 117.38±19.03*# F — 49.90 74.61 12.82 14.89 7.69 8.54 P — <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 MS组内 — 0.036 0.036 47.622 56.873 494.634 445.402 q检验:与脑梗死组比较*P < 0.05,**P < 0.01;与4.5 h溶栓组比较#P < 0.05,##P < 0.01;组内与3 d比较▲P < 0.05 -
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