Cystatin C In The Prevention Of CVS After Experimental Subarachnoid Hemorrhage And Its Relationship To Autophagy：a Preliminary Study

Objective: To investigate the expressions of autophagy in BA(basilar artery) wallsfollowing subarachnoid hemorrhage (SAH) in rats,and to study the effect of cystatin C inthe prevention of cerebral vasospasm （CVS）and its relationships to autophagy.Methods:50health male Sprague-Dawley(SD) rats were assigned randomly intofollowing groups: Control group(injected normal sodium into cisterna magna only), SAHgroup, Vehicle group, Cystatin C therapy group（divided into high and low concentrationgroups）(n=10，respectively). All SAH animals were subjected to injection of0.3ml fresharterial, nonheparinized blood into Cisterna magna to establish SAH model in rats.30minutes before the blood injection, a amount of0.1ml different doses of the Cystatin C(2μg/0.1ml or10μg/0.1ml) was administered directly into the cisterna magna in the Cys-tatin C therapy groups, while Vehicle animals received an equal volume of NS into thecisterna magna.48hours later, we observed morphological changes and the expression ofautophagy in BA walls by pathological section and Western blot analysis.Results: The inner perimeter of basal arteries (BA) in SAH group and Vehiclegroup gets smaller, and the wall thickness of basal arteries becomes thicker than controlgroup(P＜0.01), we can note the luminal narrowing, icreased wall thickness, and corruga-tion of the tunica intima in the above two groups. Compared with SAH and Vehicle groups,the inner perimeter of BA in treatment group was expanded and thickness of BA wallswere decreased with a statistical difference (P <0.01), especially in high concentrationgroup（Compared with low concentration group, P <0.05）. Western blot results showed:the expression of autophagy in BA walls was low in control group, the activity of auto-phagy was significantly increased in the rats of SAH and vehicle groups（Compared with control group, P <0.05）,the increased activity of autophagy was further markedlyupregulated by CysC treatment, especially in high concentration group（Compared withSAH and low concentration group, P <0.01and P <0.05,respectively）.Conclusions:1.The pathological changes including morphological changes, lu-minal narrowing, icreased wall thickness in BA wall suggest that CVS happens after SAH.2. The level of expression of autophagy is low in the normal control group.3. The in-creased expression of autophagy in the BA walls following SAH suggests that autophagymay participate the pathological course of CVS.4. Activation of autophagy induced byCysC resulted in attenuation of CVS in SAH models, and this effect was paralleled withthe intensity of autophagy in the BA wall induced by CysC.