强力霉素对不同时间溶栓大鼠的神经保护作用

Neuroprotective Effects of Doxycycline on Thrombolysis Therapy at Different Time in Rats

目的观察强力霉素对缺血性脑卒中不同时间(6,9,12h)尿激酶溶栓治疗效果和并发症的影响,探讨强力霉素对溶栓大鼠的神经保护作用及其对溶栓时间范围的干预效果。方法健康成年雄性SD大鼠168只,随机分为7组:缺血对照组、不同时间尿激酶溶栓组(6hUK组、9hUK组、12hUK组)、强力霉素联合尿激酶溶栓组(6hUK+Doxy组、9hUK+Doxy组、12hUK+Doxy组)各24只,均在24h后处死,分别测定MMP-9表达、脑梗死体积、血脑屏障通透性和脑出血量(各6只)。除缺血对照组外,其他各组在相应时间点给予尿激酶40000U·kg-1。联合治疗各组强力霉素在缺血后2h稀释30mg·kg-1经尾静脉注射。结果时间范围(6h)内尿激酶溶栓治疗降低脑梗死体积,联合治疗组疗效更优。超过时间范围溶栓MMP-9表达进一步增高,加重血脑屏障破坏和脑出血,强力霉素联合尿激酶溶栓治疗的各组与相应时间点单用尿激酶组比较MMP-9表达显著降低,脑梗死体积降低,血脑屏障通透性和脑出血量均有改善。结论强力霉素可提高不同时间尿激酶溶栓治疗效果,减轻溶栓并发症,对脑缺血不同时间尿激酶溶栓具有神经保护作用,有延长溶栓时间范围的可能。

Objective To study the influence of doxycycline on urokinase thrombolysis therapy at different time（6,9, 12 h）of cerebral arterial thrombosis,and evaluate its neuroproteetive effects and intervention of thrombolysis time window. Methods 168 healthy male SD rats were randomly divided into 7 groups： cerebral ischemia rats as model, urokinase thrombolysis at different time （6 hUK,9 hUK,and 12 hUK groups） , and doxycycline on urokinase thrombolysis （6 hUK ＋ Doxy, 9 hUK ＋ Doxy, and 12 hUK ＋ Doxy groups ）. Rats were all sacrified after 24 h. The expression of MMP-9 was detected with immunohistochemical staining. Trc staining were applied to detect the infarction volume. The permeability of the observed brainblood barrier was detected with Evan＇s blue and cerebral hemorrhage was quantified with spectrophotometer assay. Doxycycline was injected through tail vein 2 h postischemia at 30 mg · kg^-1. Results The infarction volumes were decreased with urokinase treatment at the 6th hour. The expression of MMP-9, permeability of the brain-blood barrier and cerebral hemorrhage content were further raised with urokinase thrombolysis at more than 6 hours after ischemic stroke, however, those were decreased and improved by doxycycline. Conclusion Doxyeyeline could increase the effect of urokinase and decrease its complications in rats at different time. It has neuroprotective effects and may extend urokinase thrombolysis therapy time window.