重组链激酶预防蛛网膜下腔出血后脑血管痉挛的实验研究

Experimental study of preventive effect of recombinant streptokinase on cerebral vasospasm after subarachnoid hemorrhage

目的研究重组链激酶(r-SK)对蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的预防作用。方法采用枕大池二次注血法制成大白兔SAH模型,24h后经侧脑室穿刺置管,治疗1组注入1.25mgr-SK,闭管6h后开放引流,6h后再次注射、闭管、引流,如此反复3次;治疗2组一次性注入r-SK3.75mg;SAH组注入生理盐水1ml,方法同治疗1组;给药后6h、12h和1d、3d、5d、7d经各引流管引流的脑脊液(CSF)用于检测氧合血红蛋白(OxyHb)含量;制模前及制模后7d分别进行基底动脉(BA)造影,计算口径比,并进行组织学检查。结果(1)CSF中OxyHb含量SAH组逐渐上升,治疗1组、2组逐渐下降,注药后1～7d治疗1组、2组OxyHb含量较SAH组明显下降(P<0.05～0.01);第7d治疗1组OxyHb含量显著低于治疗2组(P<0.05)。(2)SAH组BA管径明显缩小,呈重度痉挛;治疗1组、2组管径无明显变化。(3)组织学检查发现SAH组脑底表面有含铁血黄素沉着,血管周围有血凝块,BA内膜皱缩;治疗1组脑底无含铁血黄素沉着及血凝块,BA未见病理改变;治疗2组脑底有少量含铁血黄素沉着及血凝块,BA内膜轻度皱缩。结论侧脑室短期、少量反复注射r-SK并CSF引流可预防SAH后CVS的发生。

Objective To study the preventive effect of recombinant streptokinase （r-SK） on cerebral vasospasm （CVS） after subarachnoid hemorrhage （SAH）. Methods Rabbit models of SAH were made by double blood injection into cisterna magna. A tube was inserted into lateral ventricle after 24 h. In group treating one, 1.25 mg r-SK were injected into lateral ventricle, and the tube was opened for drainage after closed 6 h, and then 6 h later, injection, closed pipe and drainage were recycled for another 2 times. In the group SAH , 1 ml normal saline （NS） was injected into lateral ventricle, and then the way was the same as group treating one. In group treating two, 3.75 mg r-SK were injected for once. 6 h, 12 h , 1 d, 3 d, 5 d and 7 d later, 1 ml CSF was drained from the lateral ventricle in groups SAH , treating one and treating two , respectively. The level of OxyHb in CSF was detected, angiograms of basilar artery（BA） were performed before and after 7 d of SAH, calculation the rate of calibre and histological examinations were also performed. Results （ 1 ） The level of OxyHb in CSF of group SAH was increased gradually while decreased in groups treating one and treating two. Compared with group SAH, the levels Of OxyHb were significant lower in groups treating one and treating two at 1 - 7 d after administration （ P 〈 0. 05 - 0. 01 ） ; and there was obviously difference between groups treating one and treating two at 7 d after administration （P 〈 0. 05）. （2） CVS of BA were found in group SAH and no change occurred for groups treating one and treating two. （3 3 The histology showed that in group SAH there was hemosiderin pigmentation in surface of pavimentum cerebri , blood clot was around blood vessel, the endomembrane of BA was shrinkage. However, in group treating one, BA was no change and no blood clot around blood vessel. In group treating two, there was a little pigmentation in-surface of pavimentum cerebrilighter and the endomembrane of BA was shrinkage gently , no blood clot was around blood vessel. Conclusion Repeated injections with lower dosage of r-Sk into lateral ventricle and CSF drainage is a good method for prevention from CVS after SAH.