Plasma-type gelsolin is decreased in human blood and cerebrospinal fluid after subarachnoid hemorrhage.
Plasma-type gelsolin is decreased in human blood and cerebrospinal fluid after subarachnoid hemorrhage.
复制标题
DOI：
10.1161/strokeaha.111.631135
复制
发表时间：
2011-12
期刊：
影响因子：
8.3
通讯作者：
Ning M
中科院分区：
文献类型：
--
作者：
Chou SH;Lee PS;Konigsberg RG;Gallacci D;Chiou T;Arai K;Simmons S;Bauer D;Feske SK;Lo EH;Ning M
蛛网膜下腔出血（SAH）的病理生理学涉及神经血管蛋白水解和炎症。这两种现象之间的关系尚不清楚。我们假设基质金属蛋白酶（MMPs）介导的抗炎血浆型凝溶胶蛋白（pGSN）的消耗。我们招募了42名连续的SAH受试者，并在SAH后第2-3、4-5、6-7和10-14天采集CSF和血液样本。对照受试者为20例连续非SAH脑积水患者，采用腰椎引流。丽莎、Western blotting和酶谱法对pGSN和MMP-9进行定量。在CSF中，在SAH后第2-3天（p =0.0007）、第4-5天（p =0.041）和第10-14天（p=0.007），SAH中的pGSN低于对照受试者。在血液中，pGSN随时间降低（p=0.001），并且在SAH后第4-5天（p=0.037）、第6-7天（p=0.006）和第10-14天（p= 0.006），SAH中的pGSN低于对照受试者。Western印迹表明SAH CSF在52和46 kD处具有新条带，代表裂解的pGSN片段。明胶酶谱显示SAH组脑脊液MMP-9水平较对照组明显升高。在SAH后第7天，较高的CSF MMP-9与较低的CSF pGSN相关（r=-0.38; p= 0.05）。SAH与CSF和血液pGSN降低以及CSF MMP-9升高相关。SAH受试者的CSF中存在新的切割的pGSN片段，这与MMP对pGSN的切割一致。由于已知pGSN可抑制炎症介质，因此这些发现表明MMPs可减少pGSN并加重SAH后的炎症。MMP-pGSN信号通路在SAH中的作用机制有待进一步研究。
Subarachnoid hemorrhage (SAH) pathophysiology involves neurovascular proteolysis and inflammation. How these two phenomena are related remains unclear. We hypothesize that matrix metalloproteinases (MMPs) mediate the depletion of anti-inflammatory plasma-type-gelsolin (pGSN). We enrolled 42 consecutive SAH subjects and sampled CSF and blood on post-SAH days 2–3, 4–5, 6–7, and 10–14. Controls subjects were 20 consecutive non-SAH hydrocephalus patients with lumbar-drains. LISA, western blotting and zymography were used to quantify pGSN and MMP-9. In CSF, pGSN was lower in SAH compared with control subjects on post-SAH days 2–3 (p =0.0007), 4–5 (p=0.041), and 10–14 (p=0.007). In blood, pGSN decreased over time (p=0.001), and was lower in SAH compared to control subjects on post-SAH days 4–5 (p=0.037), 6–7 (p=0.006), and 10–14 (p=0.006). Western blots demonstrated that SAH CSF had novel bands at 52 and 46 kD, representing cleaved pGSN fragments. Gelatin zymography showed that CSF MMP-9 was elevated in SAH compared with controls. Higher CSF MMP-9 correlated with lower CSF pGSN on post-SAH day 7 (r= −0.38; p= 0.05). SAH is associated with decreased CSF and blood pGSN and elevated CSF MMP-9. Novel cleaved pGSN fragments are present in CSF of SAH subjects, consistent with pGSN cleavage by MMPs. Since pGSN is known to inhibit inflammatory mediators, these findings suggest that MMPs may reduce pGSN and exacerbate inflammation after SAH. Further studies are warranted to investigate the mechanisms underlying MMP-pGSN signaling in SAH.