Effect of Salvianolate Lyophilized Injection and Xueshuantong Injection (Lyophilized) on Permeability of Blood-brain Barrier via Inhibition of MMPs in Cerebral Ischemia/Reperfusion Injury Rats / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of salvianolate lyophilized injection and Xueshuantong injection (lyophilized) on the permeability of blood-brain barrier (BBB) via inhibition of metallomatrix protease（MMPs） in cerebral ischemia/reperfusion injury rats. Method:The focal cerebral ischemia/reperfusion model in rats was built by middle cerebral artery occlusion/reperfusion (MCAO/R) technique. Male Wistar rats were randomly divided into sham operation group, ischemia/reperfusion (I/R) group, edaravone (Eda, 6 mg·kg-1) group, salvianolate lyophilized injection (SLI, 21 mg·kg-1) group, Xueshuantong (XST, 100 mg·kg-1) group and SLI combined with XST (SLI+XST, 21 mg·kg-1+100 mg·kg-1) group. Drugs were injected via tail vein for 2 d, while sham group and I/R group were injected with the same amount of normal saline. Neurological deficit score, hematoxylin-eosin (HE) staining and Nissl staining were assessed 2 d after MCAO/R. The permeability of BBB was observed by the leakage of IgG/CD31. The expressions of Claudin-5，Occludin，collagen-Ⅳ（Col- Ⅳ），Laminin，Fibronectin were observed by immunofluorescence staining，and MMP-2 and MMP-9 were observed by Western blot. Result:Compared with the I/R group, SLI group, XST group and SLI+XST group showed improvements in neurological deficit score, HE staining and Nissl staining. The leakage of IgG was alleviated; The positive expressions of Claudin-5，Occludin，Col-Ⅳ，Laminin，Fibronectin in ischemic penumbra were significantly up-regulated, while the expressions of MMP-2 and MMP-9 were down-regulated. The effect in improving SLI combined with XST was much better than a single factor. Conclusion:Salvianolate lyophilized injection and Xueshuantong injection (lyophilized) can alleviate cerebral ischemia/reperfusion injury and exert the synergistic effect when they are used in combination. The mechanisms might be associated with the improvement in the permeability of blood-brain barrier by inhibiting MMPs in cerebral ischemia/reperfusion injury rats.